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Carotenoids as Anticancer Agents

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Carotenoids: Structure and Function in the Human Body

Abstract

Carotenoids are fat-soluble naturally occurring pigment commonly found in food, fruits, and vegetable. Daily intake of carotenoids has been regarded to boost disease preventing capacity. Several preclinical studies demonstrated the anticancer activity of carotenoids via targeting multiple molecular events. They are regarded to prevent carcinogenesis and inhibit cancer metastasis. Carotenoids have been proposed to act by suppressing cell proliferation and inducing apoptosis. Numbers of carotenoids including lycopene, crocin, β-carotenoid, lutein, zeaxanthin, β-cryptoxanthin, astaxanthin, and fucoxanthin possess significant cancer inhibitory potency via modulating various cell signaling events. This chapter emphasizes detailed molecular insights of anti-anticancer activity of carotenoids.

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References

  1. Martínez Andrade KA, Lauritano C, Romano G, Ianora A (2018) Marine microalgae with anti-cancer properties. Mar Drugs 16(5):165

    Article  PubMed Central  CAS  Google Scholar 

  2. D’Souza N, Murthy N, Aras R (2013) Projection of burden of cancer mortality for India, 2011–2026. Asian Pac J Cancer Prev 14(7):4387–4392

    Article  PubMed  Google Scholar 

  3. Bhandari PR (2015) Crocus sativus L.(saffron) for cancer chemoprevention: a mini review. J Tradit Complement Med 5(2):81–87

    Article  PubMed  PubMed Central  Google Scholar 

  4. Tanaka T, Shnimizu M, Moriwaki H (2012) Cancer chemoprevention by carotenoids. Molecules 17(3):3202–3242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ziegler RG (1989) A review of epidemiologic evidence that carotenoids reduce the risk of cancer. J Nutr 119(1):116–122

    Article  CAS  PubMed  Google Scholar 

  6. Murakoshi M, Nishino H, Satomi Y, Takayasu J, Hasegawa T, Tokuda H et al (1992) Potent preventive action of α-carotene against carcinogenesis: spontaneous liver carcinogenesis and promoting stage of lung and skin carcinogenesis in mice are suppressed more effectively by α-carotene than by β-carotene. Cancer Res 52(23):6583–6587

    CAS  PubMed  Google Scholar 

  7. Wang X-D, Liu C, Bronson RT, Smith DE, Krinsky NI, Russell RM (1999) Retinoid signaling and activator protein-1 expression in ferrets given β-carotene supplements and exposed to tobacco smoke. J Natl Cancer Inst 91(1):60–66

    Article  CAS  PubMed  Google Scholar 

  8. Ansari M, Gupta N (2003) A comparison of lycopene and orchidectomy vs orchidectomy alone in the management of advanced prostate cancer. BJU Int 92(4):375–378

    Article  CAS  PubMed  Google Scholar 

  9. Aung H, Wang C, Ni M, Fishbein A, Mehendale S, Xie J et al (2007) Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol 29(3):175

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Van Helden YG, Keijer J, Heil SG, Picó C, Palou A, Oliver P et al (2009) Beta-carotene affects oxidative stress-related DNA damage in lung epithelial cells and in ferret lung. Carcinogenesis 30(12):2070–2076

    Article  PubMed  CAS  Google Scholar 

  11. Terasaki M, Maeda H, Miyashita K, Mutoh M (2017) Induction of anoikis in human colorectal cancer cells by fucoxanthinol. Nutr Cancer 69(7):1043–1052

    Article  CAS  PubMed  Google Scholar 

  12. Liou G-Y, Storz P (2010) Reactive oxygen species in cancer. Free Radic Res 44(5):479–496

    Article  CAS  PubMed  Google Scholar 

  13. Tafani M, Sansone L, Limana F, Arcangeli T, De Santis E, Polese M et al (2016) The interplay of reactive oxygen species, hypoxia, inflammation, and sirtuins in cancer initiation and progression. Oxidative Med Cell Longev 2016:3907147. https://doi.org/10.1155/2016/3907147.

  14. Prasad S, Gupta SC, Tyagi AK (2017) Reactive oxygen species (ROS) and cancer: role of antioxidative nutraceuticals. Cancer Lett 387:95–105

    Article  CAS  PubMed  Google Scholar 

  15. Cook JA, Gius D, Wink DA, Krishna MC, Russo A, Mitchell JB (2004) Oxidative stress, redox, and the tumor microenvironment. Semin Radiat Oncol 14:259–266.

    Google Scholar 

  16. Gottschling BC, Maronpot RR, Hailey JR, Peddada S, Moomaw CR, Klaunig JE et al (2001) The role of oxidative stress in indium phosphide-induced lung carcinogenesis in rats. Toxicol Sci 64(1):28–40

    Article  CAS  PubMed  Google Scholar 

  17. Miyake H, Hara I, Kamidono S, Eto H (2004) Oxidative DNA damage in patients with prostate cancer and its response to treatment. J Urol 171(4):1533–1536

    Article  CAS  PubMed  Google Scholar 

  18. Weiss J, Goode EL, Ladiges W, Ulrich CM (2005) Polymorphic variation in hOGG1 and risk of cancer: a review of the functional and epidemiologic literature. Mol Carcinogen 42(3):127–141. Published in cooperation with the University of Texas MD Anderson Cancer Center

    Article  CAS  Google Scholar 

  19. Diakowska D, Lewandowski A, Kopeć W, Diakowski W, Chrzanowska T (2007) Oxidative DNA damage and total antioxidant status in serum of patients with esophageal squamous cell carcinoma. Hepato-Gastroenterology 54(78):1701–1704

    CAS  PubMed  Google Scholar 

  20. Muguruma M, Unami A, Kanki M, Kuroiwa Y, Nishimura J, Dewa Y et al (2007) Possible involvement of oxidative stress in piperonyl butoxide induced hepatocarcinogenesis in rats. Toxicology 236(1–2):61–75

    Article  CAS  PubMed  Google Scholar 

  21. Galadari S, Rahman A, Pallichankandy S, Thayyullathil F (2017) Reactive oxygen species and cancer paradox: to promote or to suppress? Free Radic Biol Med 104:144–164

    Article  CAS  PubMed  Google Scholar 

  22. Vara JÁF, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M (2004) PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 30(2):193–204

    Article  CAS  Google Scholar 

  23. Klaunig JE, Kamendulis LM, Hocevar BA (2010) Oxidative stress and oxidative damage in carcinogenesis. Toxicol Pathol 38(1):96–109

    Article  CAS  PubMed  Google Scholar 

  24. Waris G, Ahsan H (2006) Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinogen 5:14

    Article  CAS  Google Scholar 

  25. Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134(12):3479S–3485S

    Article  CAS  PubMed  Google Scholar 

  26. Young AJ, Lowe GM (2001) Antioxidant and prooxidant properties of carotenoids. Arch Biochem Biophys 385(1):20–27

    Article  CAS  PubMed  Google Scholar 

  27. Valko M, Izakovic M, Mazur M, Rhodes CJ, Telser J (2004) Role of oxygen radicals in DNA damage and cancer incidence. Mol Cell Biochem 266(1–2):37–56

    Article  CAS  PubMed  Google Scholar 

  28. Tinkler JH, Böhm F, Schalch W, Truscott TG (1994) Dietary carotenoids protect human cells from damage. J Photochem Photobiol B Biol 26(3):283–285

    Article  CAS  Google Scholar 

  29. Böhm F, Edge R, Burke M, Truscott T (2001) Dietary uptake of lycopene protects human cells from singlet oxygen and nitrogen dioxide–ROS components from cigarette smoke. J Photochem Photobiol B Biol 64(2–3):176–178

    Article  Google Scholar 

  30. Handelman GJ, Packer L, Cross CE (1996) Destruction of tocopherols, carotenoids, and retinol in human plasma by cigarette smoke. Am J Clin Nutr 63(4):559–565

    Article  CAS  PubMed  Google Scholar 

  31. Mortensen A, Skibsted LH, Sampson J, Rice-Evans C, Everett SA (1997) Comparative mechanisms and rates of free radical scavenging by carotenoid antioxidants. FEBS Lett 418(1–2):91–97

    Article  CAS  PubMed  Google Scholar 

  32. Rezaee R, Jamialahmadi K, Zanjani BR, Mahmoudi M, Abnous K, Rabe SZT et al (2014) Crocin effects on human myeloma cells regarding intracellular redox state, DNA fragmentation, and apoptosis or necrosis profile. Jundishapur J Nat Pharm Prod 9(4):e20131

    Article  PubMed  PubMed Central  Google Scholar 

  33. Palozza P, Serini S, Torsello A, Boninsegna A, Covacci V, Maggiano N et al (2002) Regulation of cell cycle progression and apoptosis by β-carotene in undifferentiated and differentiated HL-60 leukemia cells: possible involvement of a redox mechanism. Int J Cancer 97(5):593–600

    Article  CAS  PubMed  Google Scholar 

  34. Upadhyaya K, Radha K, Madhyastha H (2007) Cell cycle regulation and induction of apoptosis by β-carotene in U937 and HL-60 leukemia cells. BMB Rep 40(6):1009–1015

    Article  CAS  Google Scholar 

  35. Hosokawa M, Wanezaki S, Miyauchi K, Kurihara H, Kohno H, Kawabata J et al (1999) Apoptosis-inducing effect of fucoxanthin on human leukemia cell line HL-60. Food Sci Technol Res 5(3):243–246

    Article  CAS  Google Scholar 

  36. Gradelet S, Le Bon A, Berges R, Suschetet M, Astorg P (1998) Dietary carotenoids inhibit aflatoxin B1-induced liver preneoplastic foci and DNA damage in the rat: role of the modulation of aflatoxin B1 metabolism. Carcinogenesis 19(3):403–411

    Article  CAS  PubMed  Google Scholar 

  37. Chew B, Park J, Wong M, Wong T (1999) A comparison of the anticancer activities of dietary beta-carotene, canthaxanthin and astaxanthin in mice in vivo. Anticancer Res 19(3A):1849–1853

    CAS  PubMed  Google Scholar 

  38. Lyons NM, O’Brien NM (2002) Modulatory effects of an algal extract containing astaxanthin on UVA-irradiated cells in culture. J Dermatol Sci 30(1):73–84

    Article  CAS  PubMed  Google Scholar 

  39. Serpeloni JM, Barcelos GRM, Angeli JPF, Mercadante AZ, Bianchi MLP, Antunes LMG (2012) Dietary carotenoid lutein protects against DNA damage and alterations of the redox status induced by cisplatin in human derived HepG2 cells. Toxicol In Vitro 26(2):288–294

    Article  CAS  PubMed  Google Scholar 

  40. Kotake-Nara E, Kushiro M, Zhang H, Sugawara T, Miyashita K, Nagao A (2001) Carotenoids affect proliferation of human prostate cancer cells. J Nutr 131(12):3303–3306

    Article  CAS  PubMed  Google Scholar 

  41. Konishi I, Hosokawa M, Sashima T, Kobayashi H, Miyashita K (2006) Halocynthiaxanthin and fucoxanthinol isolated from Halocynthia roretzi induce apoptosis in human leukemia, breast and colon cancer cells. Comp Biochem Physiol C Toxicol Pharmacol 142(1–2):53–59

    Article  PubMed  CAS  Google Scholar 

  42. Tibodeau JD, Isham CR, Bible KC (2010) Annatto constituent cis-bixin has selective antimyeloma effects mediated by oxidative stress and associated with inhibition of thioredoxin and thioredoxin reductase. Antioxid Redox Signal 13(7):987–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Dewanjee S, Das S, Das AK, Bhattacharjee N, Dihingia A, Dua TK et al (2018) Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets. Eur J Pharmacol 833:472–523

    Article  CAS  PubMed  Google Scholar 

  44. Hu X-Y, Hou P-F, Li T-T, Quan H-Y, Li M-L, Lin T et al (2018) The roles of Wnt/β-catenin signaling pathway related lncRNAs in cancer. Int J Biol Sci 14(14):2003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Ochoa-Hernández AB, Juárez-Vázquez CI, Rosales-Reynoso MA, Barros-Núñez P (2012) Wnt-β-catenin signaling pathway and its relationship with cancer. Cir Cir 80:362–370

    Google Scholar 

  46. Voeller HJ, Truica CI, Gelmann EP (1998) β-Catenin mutations in human prostate cancer. Cancer Res 58(12):2520–2523

    CAS  PubMed  Google Scholar 

  47. Chesire DR, Ewing CM, Sauvageot J, Bova GS, Isaacs WB (2000) Detection and analysis of β-catenin mutations in prostate cancer. Prostate 45(4):323–334

    Article  CAS  PubMed  Google Scholar 

  48. Sun X, Liu Y (2017) Activation of the Wnt/β-catenin signaling pathway may contribute to cervical cancer pathogenesis via upregulation of Twist. Oncol Lett 14(4):4841–4844

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Li J, Dai W, Xia Y, Chen K, Li S, Liu T et al (2015) Astaxanthin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells via inhibition of NF-κB P65 and Wnt/β-catenin in vitro. Mar Drugs 13(10):6064–6081

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kavitha K, Kowshik J, Kishore TKK, Baba AB, Nagini S (2013) Astaxanthin inhibits NF-κB and Wnt/β-catenin signaling pathways via inactivation of Erk/MAPK and PI3K/Akt to induce intrinsic apoptosis in a hamster model of oral cancer. Biochim Biophys Acta 1830(10):4433–4444

    Article  CAS  PubMed  Google Scholar 

  51. Tang FY, Shih CJ, Cheng LH, Ho HJ, Chen HJ (2008) Lycopene inhibits growth of human colon cancer cells via suppression of the Akt signaling pathway. Mol Nutr Food Res 52(6):646–654

    Article  CAS  PubMed  Google Scholar 

  52. Lin M-C, Wang F-Y, Kuo Y-H, Tang F-Y (2011) Cancer chemopreventive effects of lycopene: suppression of MMP-7 expression and cell invasion in human colon cancer cells. J Agric Food Chem 59(20):11304–11318

    Article  CAS  PubMed  Google Scholar 

  53. Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M (2004) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet 363(9418):1346–1353

    Article  CAS  PubMed  Google Scholar 

  54. Fürstenberger G, Senn H-J (2002) Insulin-like growth factors and cancer. Lancet Oncol 3(5):298–302

    Article  PubMed  Google Scholar 

  55. Stoeltzing O, Liu W, Reinmuth N, Fan F, Parikh AA, Bucana CD et al (2003) Regulation of hypoxia-inducible factor-1α, vascular endothelial growth factor, and angiogenesis by an insulin-like growth factor-I receptor autocrine loop in human pancreatic cancer. Am J Pathol 163(3):1001–1011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kopantzev E, Grankina E, Kopantseva M, Sverdlov E (2017) The IGF-I/IGF-IR signaling system and pancreatic Cancer. Mol Genet Microbiol Virol 32(3):131–136

    Article  Google Scholar 

  57. Tang Y, Parmakhtiar B, Simoneau AR, Xie J, Fruehauf J, Lilly M et al (2011) Lycopene enhances docetaxel’s effect in castration-resistant prostate cancer associated with insulin-like growth factor I receptor levels. Neoplasia (New York, NY) 13(2):108

    Article  CAS  Google Scholar 

  58. Levy J, Bosin E, Feldman B, Giat Y, Miinster A, Danilenko M et al (1995) Lycopene is a more potent inhibitor of human cancer cell proliferation than either α-carotene or β-carotene. Nutr Cancer 24(3):257–266

    Article  CAS  PubMed  Google Scholar 

  59. Santana-Codina N, Mancias JD, Kimmelman AC (2017) The role of autophagy in cancer. Annu Rev Cancer Biol 1:19–39

    Article  PubMed  PubMed Central  Google Scholar 

  60. Kung C-P, Budina A, Balaburski G, Bergenstock MK, Murphy M (2011) Autophagy in tumor suppression and cancer therapy. Crit Rev Eukaryot Gene Expr 21(1):145

    Article  Google Scholar 

  61. Zhang Z, Shao Z, Xiong L, Che B, Deng C, Xu W (2009) Expression of Beclin1 in osteosarcoma and the effects of down-regulation of autophagy on the chemotherapeutic sensitivity. J Huazhong Univ Sci Technol [Med Sci] 29(6):737

    Article  CAS  Google Scholar 

  62. Cai M, Hu Z, Liu J, Gao J, Liu C, Liu D et al (2014) Beclin 1 expression in ovarian tissues and its effects on ovarian cancer prognosis. Int J Mol Sci 15(4):5292–5303

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  63. Qiu D-M, Wang G-L, Chen L, Xu Y-Y, He S, Cao X-L et al (2014) The expression of beclin-1, an autophagic gene, in hepatocellular carcinoma associated with clinical pathological and prognostic significance. BMC Cancer 14(1):327

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Singh SS, Vats S, Chia AY-Q, Tan TZ, Deng S, Ong MS et al (2018) Dual role of autophagy in hallmarks of cancer. Oncogene 37(9):1142–1158

    Article  CAS  PubMed  Google Scholar 

  65. Takamura A, Komatsu M, Hara T, Sakamoto A, Kishi C, Waguri S et al (2011) Autophagy-deficient mice develop multiple liver tumors. Genes Dev 25(8):795–800

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Nicotra G, Mercalli F, Peracchio C, Castino R, Follo C, Valente G et al (2010) Autophagy-active beclin-1 correlates with favourable clinical outcome in non-Hodgkin lymphomas. Mod Pathol 23(7):937–950

    Article  CAS  PubMed  Google Scholar 

  67. Wei H, Wei S, Gan B, Peng X, Zou W, Guan J-L (2011) Suppression of autophagy by FIP200 deletion inhibits mammary tumorigenesis. Genes Dev 25(14):1510–1527

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Chen N, Karantza-Wadsworth V (2009) Role and regulation of autophagy in cancer. Biochim Biophys Acta Mol Cell Res 1793(9):1516–1523

    Article  CAS  Google Scholar 

  69. Hou L-L, Gao C, Chen L, Hu G-Q, Xie S-Q (2013) Essential role of autophagy in fucoxanthin-induced cytotoxicity to human epithelial cervical cancer HeLa cells. Acta Pharmacol Sin 34(11):1403–1410

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Amin A, Bajbouj K, Koch A, Gandesiri M, Schneider-Stock R (2015) Defective autophagosome formation in p53-null colorectal cancer reinforces crocin-induced apoptosis. Int J Mol Sci 16(1):1544–1561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Luo J, Manning BD, Cantley LC (2003) Targeting the PI3K-Akt pathway in human cancer: rationale and promise. Cancer Cell 4(4):257–262

    Article  CAS  PubMed  Google Scholar 

  72. Vivanco I, Sawyers CL (2002) The phosphatidylinositol 3-kinase–AKT pathway in human cancer. Nat Rev Cancer 2(7):489–501

    Article  CAS  PubMed  Google Scholar 

  73. Martini M, De Santis MC, Braccini L, Gulluni F, Hirsch E (2014) PI3K/AKT signaling pathway and cancer: an updated review. Ann Med 46(6):372–383

    Article  CAS  PubMed  Google Scholar 

  74. Shayesteh L, Lu Y, Kuo W-L, Baldocchi R, Godfrey T, Collins C et al (1999) PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet 21(1):99–102

    Article  CAS  PubMed  Google Scholar 

  75. Bellacosa A, De Feo D, Godwin AK, Bell DW, Cheng JQ, Altomare DA et al (1995) Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer 64(4):280–285

    Article  CAS  PubMed  Google Scholar 

  76. Cheng JQ, Ruggeri B, Klein WM, Sonoda G, Altomare DA, Watson DK et al (1996) Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci 93(8):3636–3641

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Shukla S, MacLennan GT, Hartman DJ, Fu P, Resnick MI, Gupta S (2007) Activation of PI3K-Akt signaling pathway promotes prostate cancer cell invasion. Int J Cancer 121(7):1424–1432

    Article  CAS  PubMed  Google Scholar 

  78. Youssef J, Badr M (2011) Peroxisome proliferator-activated receptors and cancer: challenges and opportunities. Br J Pharmacol 164(1):68–82

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Reddy RC, Srirangam A, Reddy K, Chen J, Gangireddy S, Kalemkerian GP et al (2008) Chemotherapeutic drugs induce PPAR-γ expression and show sequence-specific synergy with PPAR-γ ligands in inhibition of non-small cell lung cancer. Neoplasia (New York, NY) 10(6):597

    Article  CAS  Google Scholar 

  80. Motawi T, Shaker O, Ismail M, Sayed N (2017) Peroxisome proliferator-activated receptor gamma in obesity and colorectal cancer: the role of epigenetics. Sci Rep 7(1):1–8

    Article  CAS  Google Scholar 

  81. Terashita Y, Sasaki H, Haruki N, Nishiwaki T, Ishiguro H, Shibata Y et al (2002) Decreased peroxisome proliferator-activated receptor gamma gene expression is correlated with poor prognosis in patients with esophageal cancer. Jpn J Clin Oncol 32(7):238–243

    Article  PubMed  Google Scholar 

  82. Jung T-I, Baek W-K, Suh S-I, Jang B-C, Song D-K, Bae J-H et al (2005) Down-regulation of peroxisome proliferator-activated receptor gamma in human cervical carcinoma. Gynecol Oncol 97(2):365–373

    Article  CAS  PubMed  Google Scholar 

  83. Zaytseva YY, Wang X, Southard RC, Wallis NK, Kilgore MW (2008) Down-regulation of PPARgamma1 suppresses cell growth and induces apoptosis in MCF-7 breast cancer cells. Mol Cancer 7(1):90

    Article  PubMed  PubMed Central  Google Scholar 

  84. Zhao W-E, Shi G, Gu H, Nguyen BN (2016) Role of PPARγ in the nutritional and pharmacological actions of carotenoids. Res Rep Biochem 6:13

    Google Scholar 

  85. Semple RK, Chatterjee VKK, O’Rahilly S (2006) PPARγ and human metabolic disease. J Clin Invest 116(3):581–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Xia L, Tan S, Zhou Y, Lin J, Wang H, Oyang L et al (2018) Role of the NFκB-signaling pathway in cancer. Onco Targets Ther 11:2063–2073

    Article  PubMed  PubMed Central  Google Scholar 

  87. Dolcet X, Llobet D, Pallares J, Matias-Guiu X (2005) NF-kB in development and progression of human cancer. Virchows Arch 446(5):475–482

    Article  CAS  PubMed  Google Scholar 

  88. Aggarwal BB, Gehlot P (2009) Inflammation and cancer: how friendly is the relationship for cancer patients? Curr Opin Pharmacol 9(4):351–369

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Jin R, Sterling JA, Edwards JR, DeGraff DJ, Lee C, Park SI et al (2013) Activation of NF-kappa B signaling promotes growth of prostate cancer cells in bone. PloS one 8(4):e60983

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Mukhopadhyay T, Roth JA, Maxwell SA (1995) Altered expression of the p50 subunit of the NF-kappa B transcription factor complex in non-small cell lung carcinoma. Oncogene 11(5):999–1003

    CAS  PubMed  Google Scholar 

  91. Sovak MA, Bellas RE, Kim DW, Zanieski GJ, Rogers AE, Traish AM et al (1997) Aberrant nuclear factor-kappaB/Rel expression and the pathogenesis of breast cancer. J Clin Invest 100(12):2952–2960

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Vasudevan KM, Gurumurthy S, Rangnekar VM (2004) Suppression of PTEN expression by NF-κB prevents apoptosis. Mol Cell Biol 24(3):1007–1021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Chaturvedi M, Sung B, Yadav V, Kannappan R, Aggarwal BB (2011) NF-κB addiction and its role in cancer:‘one size does not fit all’. Oncogene 30(14):1615–1630

    Article  CAS  PubMed  Google Scholar 

  94. Yasui Y, Hosokawa M, Mikami N, Miyashita K, Tanaka T (2011) Dietary astaxanthin inhibits colitis and colitis-associated colon carcinogenesis in mice via modulation of the inflammatory cytokines. Chem Biol Interact 193(1):79–87

    Article  CAS  PubMed  Google Scholar 

  95. Ishikawa C, Jomori T, Tanaka J, Senba M, Mori N (2016) Peridinin, a carotenoid, inhibits proliferation and survival of HTLV-1-infected T-cell lines. Int J Oncol 49(4):1713–1721

    Article  CAS  PubMed  Google Scholar 

  96. Canavese M, Santo L, Raje N (2012) Cyclin dependent kinases in cancer: potential for therapeutic intervention. Cancer Biol Ther 13(7):451–457

    Article  CAS  PubMed  Google Scholar 

  97. Geleta B, Makonnen E, Abay SM (2016) Cyclic dependent kinase (CDK): role in cancer pathogenesis and as drug target in cancer therapeutics. J Cancer Sci Ther 8(6):160–167

    Article  Google Scholar 

  98. Malumbres M, Barbacid M (2005) Mammalian cyclin-dependent kinases. Trends Biochem Sci 30(11):630–641

    Article  CAS  PubMed  Google Scholar 

  99. Biggs J, Kraft A (1995) Inhibitors of cyclin-dependent kinase and cancer. J Mol Med 73(10):509–514

    Article  CAS  PubMed  Google Scholar 

  100. Peyressatre M, Prével C, Pellerano M, Morris MC (2015) Targeting cyclin-dependent kinases in human cancers: from small molecules to peptide inhibitors. Cancers 7(1):179–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Rafi MM, Kanakasabai S, Reyes MD, Bright JJ (2013) Lycopene modulates growth and survival associated genes in prostate cancer. J Nutr Biochem 24(10):1724–1734

    Article  CAS  PubMed  Google Scholar 

  102. Liu C, Russell RM, Wang X-D (2006) Lycopene supplementation prevents smoke-induced changes in p53, p53 phosphorylation, cell proliferation, and apoptosis in the gastric mucosa of ferrets. J Nutr 136(1):106–111

    Article  CAS  PubMed  Google Scholar 

  103. Nahum A, Hirsch K, Danilenko M, Watts CK, Prall OW, Levy J et al (2001) Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells is associated with reduction in cyclin D levels and retention of p27 Kip1 in the cyclin E–cdk2 complexes. Oncogene 20(26):3428–3436

    Article  CAS  PubMed  Google Scholar 

  104. Palozza P, Colangelo M, Simone R, Catalano A, Boninsegna A, Lanza P et al (2010) Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines. Carcinogenesis 31(10):1813–1821

    Article  CAS  PubMed  Google Scholar 

  105. D’Alessandro AM, Mancini A, Lizzi AR, De Simone A, Marroccella CE, Gravina GL et al (2013) Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer. Nutr Cancer 65(6):930–942

    Article  PubMed  CAS  Google Scholar 

  106. Zhao P, Luo C, Wu X, Hu H, Lv C, Ji H (2008) Proliferation apoptotic influence of crocin on human bladder cancer T24 cell line. Zhongguo Zhong yao za zhi= Zhongguo zhongyao zazhi=. China J Chinese Materia Medica 33(15):1869–1873

    CAS  Google Scholar 

  107. Hire RR, Srivastava S, Davis MB, Konreddy AK, Panda D (2017) Antiproliferative activity of crocin involves targeting of microtubules in breast cancer cells. Sci Rep 7:44984

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Miyazawa K, Miyamoto S, Suzuki R, Yasui Y, Ikeda R, Kohno H et al (2007) Dietary β-cryptoxanthin inhibits N-butyl-N-(4-hydroxybutyl) nitrosamine-induced urinary bladder carcinogenesis in male ICR mice. Oncol Rep 17(2):297–304

    CAS  PubMed  Google Scholar 

  109. Zhang X, Zhao W-E, Hu L, Zhao L, Huang J (2011) Carotenoids inhibit proliferation and regulate expression of peroxisome proliferators-activated receptor gamma (PPARγ) in K562 cancer cells. Arch Biochem Biophys 512(1):96–106

    Article  CAS  PubMed  Google Scholar 

  110. Mahdizadeh S, Karimi G, Behravan J, Arabzadeh S, Lage H, Kalalinia F (2016) Crocin suppresses multidrug resistance in MRP overexpressing ovarian cancer cell line. DARU J Pharm Sci 24(1):17

    Article  CAS  Google Scholar 

  111. Williams CL, Phelps SH, Porter RA (1996) Expression of Ca2+/calmodulin-dependent protein kinase types II and IV, and reduced DNA synthesis due to the Ca2+/calmodulin-dependent protein kinase inhibitor KN-62 (1-[N, O-Bis (5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenylpiperazine) in small cell lung carcinoma. Biochem Pharmacol 51(5):707–715

    Article  CAS  PubMed  Google Scholar 

  112. Gretzer MB, Partin AW (2002) PSA levels and the probability of prostate cancer on biopsy. Eur Urol Suppl 1(6):21–27

    Article  Google Scholar 

  113. Yoon H, Dehart JP, Murphy JM, Lim S-TS (2015) Understanding the roles of FAK in cancer: inhibitors, genetic models, and new insights. J Histochem Cytochem 63(2):114–128

    Article  PubMed  CAS  Google Scholar 

  114. Jänicke RU, Sprengart ML, Wati MR, Porter AG (1998) Caspase-3 is required for DNA fragmentation and morphological changes associated with apoptosis. J Biol Chem 273(16):9357–9360

    Article  PubMed  Google Scholar 

  115. Debatin K-M (2004) Apoptosis pathways in cancer and cancer therapy. Cancer Immunol Immunother 53(3):153–159

    Article  PubMed  Google Scholar 

  116. Campos L, Rouault J-P, Sabido O, Oriol P, Roubi N, Vasselon C et al (1993) High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood 81(11):3091–3096

    Article  CAS  PubMed  Google Scholar 

  117. Bargou RC, Daniel PT, Mapara MY, Bommert K, Wagener C, Kallinich B et al (1995) Expression of the bcl-2 gene family in normal and malignant breast tissue: low bax-α expression in tumor cells correlates with resistance towards apoptosis. Int J Cancer 60(6):854–859

    Article  CAS  PubMed  Google Scholar 

  118. Naz H, Khan P, Tarique M, Rahman S, Meena A, Ahamad S et al (2017) Binding studies and biological evaluation of β-carotene as a potential inhibitor of human calcium/calmodulin-dependent protein kinase IV. Int J Biol Macromol 96:161–170

    Article  CAS  PubMed  Google Scholar 

  119. Bunker CH, McDonald AC, Evans RW, De La Rosa N, Boumosleh JM, Patrick AL (2007) A randomized trial of lycopene supplementation in Tobago men with high prostate cancer risk. Nutr Cancer 57(2):130–137

    Article  CAS  PubMed  Google Scholar 

  120. Grainger EM, Schwartz SJ, Wang S, Unlu NZ, Boileau TW-M, Ferketich AK et al (2008) A combination of tomato and soy products for men with recurring prostate cancer and rising prostate specific antigen. Nutr Cancer 60(2):145–154

    Article  CAS  PubMed  Google Scholar 

  121. Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F et al (2001) Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy. Cancer Epidemiol Prev Biomarkers 10(8):861–868

    CAS  Google Scholar 

  122. Mohanty NK, Saxena S, Singh UP, Goyal NK, Arora RP (2005) Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. Urol Oncol 23:383–385.

    Google Scholar 

  123. Vaishampayan U, Hussain M, Banerjee M, Seren S, Sarkar FH, Fontana J et al (2007) Lycopene and soy isoflavones in the treatment of prostate cancer. Nutr Cancer 59(1):1–7

    Article  CAS  PubMed  Google Scholar 

  124. Schwarz S, Obermüller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski H-K (2008) Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr 138(1):49–53

    Article  CAS  PubMed  Google Scholar 

  125. van Breemen RB, Sharifi R, Viana M, Pajkovic N, Zhu D, Yuan L et al (2011) Antioxidant effects of lycopene in African American men with prostate cancer or benign prostate hyperplasia: a randomized, controlled trial. Cancer Prev Res 4(5):711–718

    Article  CAS  Google Scholar 

  126. Soares NCP, Teodoro AJ, Oliveira FL, Takiya CM, Junior AP, Nasciutti LE et al (2014) Lycopene induce apoptosis in human prostate cells and alters the expression of Bax and Bcl-2 genes. LWT-Food Sci Technol 59(2):1290–1297

    Article  CAS  Google Scholar 

  127. Liu C, Lian F, Smith DE, Russell RM, Wang X-D (2003) Lycopene supplementation inhibits lung squamous metaplasia and induces apoptosis via up-regulating insulin-like growth factor-binding protein 3 in cigarette smoke-exposed ferrets. Cancer Res 63(12):3138–3144

    CAS  PubMed  Google Scholar 

  128. Hoshyar R, Bathaie SZ, Sadeghizadeh M (2013) Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells. DNA Cell Biol 32(2):50–57

    Article  CAS  PubMed  Google Scholar 

  129. Vali F, Changizi V, Safa M (2015) Synergistic apoptotic effect of crocin and paclitaxel or crocin and radiation on MCF-7 cells, a type of breast cancer cell line. Int J Breast Cancer 2015

    Google Scholar 

  130. Zhang Y, Zhu X, Huang T, Chen L, Liu Y, Li Q et al (2016) β-Carotene synergistically enhances the anti-tumor effect of 5-fluorouracil on esophageal squamous cell carcinoma in vivo and in vitro. Toxicol Lett 261:49–58

    Article  CAS  PubMed  Google Scholar 

  131. Kim K-N, Heo S-J, Kang S-M, Ahn G, Jeon Y-J (2010) Fucoxanthin induces apoptosis in human leukemia HL-60 cells through a ROS-mediated Bcl-xL pathway. Toxicol In Vitro 24(6):1648–1654

    Article  CAS  PubMed  Google Scholar 

  132. Zhang Z, Zhang P, Hamada M, Takahashi S, Xing G, Liu J et al (2008) Potential chemoprevention effect of dietary fucoxanthin on urinary bladder cancer EJ-1 cell line. Oncol Rep 20(5):1099–1103

    CAS  PubMed  Google Scholar 

  133. Kotake-Nara E, Asai A, Nagao A (2005) Neoxanthin and fucoxanthin induce apoptosis in PC-3 human prostate cancer cells. Cancer Lett 220(1):75–84

    Article  CAS  PubMed  Google Scholar 

  134. Bi M-C, Rosen R, Zha R-Y, McCormick SA, Song E, Hu D-N (2013) Zeaxanthin induces apoptosis in human uveal melanoma cells through Bcl-2 family proteins and intrinsic apoptosis pathway. Evid Based Complement Alternat Med 2013:205082. https://doi.org/10.1155/2013/205082.

  135. Choi Y-J, Hur J-M, Lim S, Jo M, Kim DH, Choi J-I (2014) Induction of apoptosis by deinoxanthin in human cancer cells. Anticancer Res 34(4):1829–1835

    CAS  PubMed  Google Scholar 

  136. Ganesan P, Noda K, Manabe Y, Ohkubo T, Tanaka Y, Maoka T et al (2011) Siphonaxanthin, a marine carotenoid from green algae, effectively induces apoptosis in human leukemia (HL-60) cells. Biochim Biophys Acta General Subjects 1810(5):497–503

    Article  CAS  Google Scholar 

  137. Liu C, Wang X-D, Bronson RT, Smith DE, Krinsky NI, Russell RM (2000) Effects of physiological versus pharmacological β-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets. Carcinogenesis 21(12):2245–2253

    Article  CAS  PubMed  Google Scholar 

  138. Pan L, Chai H-B, Kinghorn AD (2012) Discovery of new anticancer agents from higher plants. Front Biosci (Scholar edition) 4:142

    Article  CAS  Google Scholar 

  139. Gong X, Smith JR, Swanson HM, Rubin LP (2018) Carotenoid lutein selectively inhibits breast cancer cell growth and potentiates the effect of chemotherapeutic agents through ROS-mediated mechanisms. Molecules 23(4):905

    Article  PubMed Central  CAS  Google Scholar 

  140. Park JS, Chew BP, Wong TS (1998) Dietary lutein from marigold extract inhibits mammary tumor development in BALB/c mice. J Nutr 128(10):1650–1656

    Article  CAS  PubMed  Google Scholar 

  141. Gunasekera RS, Sewgobind K, Desai S, Dunn L, Black HS, McKeehan WL et al (2007) Lycopene and lutein inhibit proliferation in rat prostate carcinoma cells. HNUC 58(2):171–177

    Article  CAS  Google Scholar 

  142. Zhang W-L, Zhao Y-N, Shi Z-Z, Cong D, Bai Y-S (2018) Lutein inhibits cell growth and activates apoptosis via the PI3K/AKT/mTOR signaling pathway in A549 human non-small-cell lung cancer cells. J Environ Pathol Toxicol Oncol 37(4):341

    Article  PubMed  Google Scholar 

  143. Xu XL, Hu D-N, Iacob C, Jordan A, Gandhi S, Gierhart DL et al (2015) Effects of zeaxanthin on growth and invasion of human uveal melanoma in nude mouse model. J Ophthalmol 57:4104. https://doi.org/10.1155/2015/392305.

  144. Nishino H, Tsushima M, Matsuno T, Tanaka Y, Okuzumi J, Murakoshi M et al (1992) Anti-neoplastic effect of halocynthiaxanthin, a metabolite of fucoxanthin. Anti-Cancer Drugs 3(5):493–497

    Article  CAS  PubMed  Google Scholar 

  145. Yoshida T, Maoka T, Das SK, Kanazawa K, Horinaka M, Wakada M et al (2007) Halocynthiaxanthin and peridinin sensitize colon cancer cell lines to tumor necrosis factor–related apoptosis-inducing ligand. Mol Cancer Res 5(6):615–625

    Article  CAS  PubMed  Google Scholar 

  146. Nishino H (1991) Anti-tumor activity of peridinin and its structurelly related butenolide compounds. J Kyoto Pref Univ Med 100:831–835

    CAS  Google Scholar 

  147. Molnar J, Serly J, Pusztai R, Vincze I, Molnar P, Horváth G et al (2012) Putative supramolecular complexes formed by carotenoids and xanthophylls with ascorbic acid to reverse multidrug resistance in cancer cells. Anticancer Res 32(2):507–517

    CAS  PubMed  Google Scholar 

  148. Tokuda H, Enjo F, Maoka T, Mochida K, Kuchide M, Ogata M et al (2004) Regulation of the cell cycle progression of A549 human lung cancer cell treatment by major paprica carotenoids elements capsanthin, capsorubin and beta-carotene. Cancer Res 64:1374.

    Google Scholar 

  149. de Oliveira Júnior RG, Bonnet A, Braconnier E, Groult H, Prunier G, Beaugeard L et al (2019) Bixin, an apocarotenoid isolated from Bixa orellana L., sensitizes human melanoma cells to dacarbazine-induced apoptosis through ROS-mediated cytotoxicity. Food Chem Toxicol 125:549–561

    Article  PubMed  CAS  Google Scholar 

  150. Kumar Y, Phaniendra A, Periyasamy L (2018) Bixin triggers apoptosis of human Hep3B hepatocellular carcinoma cells: an insight to molecular and in silico approach. Nutr Cancer 70(6):971–983

    Article  CAS  PubMed  Google Scholar 

  151. Maoka T, Mochida K, Kozuka M, Ito Y, Fujiwara Y, Hashimoto K et al (2001) Cancer chemopreventive activity of carotenoids in the fruits of red paprika Capsicum annuum L. Cancer Lett 172(2):103–109

    Article  CAS  PubMed  Google Scholar 

  152. Palozza P, Maggiano N, Calviello G, Lanza P, Piccioni E, Ranelletti FO et al (1998) Canthaxanthin induces apoptosis in human cancer cell lines. Carcinogenesis 19(2):373–376

    Article  CAS  PubMed  Google Scholar 

  153. Kozuki Y, Miura Y, Yagasaki K (2000) Inhibitory effects of carotenoids on the invasion of rat ascites hepatoma cells in culture. Cancer Lett 151(1):111–115

    Article  CAS  PubMed  Google Scholar 

  154. Tanaka T, Morishita Y, Suzui M, Kojima T, Okumura A, Mori H (1994) Chemoprevention of mouse urinary bladder carcinogenesis by the naturally occurring carotenoid astaxanthin. Carcinogenesis 15(1):15–19

    Article  CAS  PubMed  Google Scholar 

  155. Tanaka T, Makita H, Ohnishi M, Mori H, Satoh K, Hara A (1995) Chemoprevention of rat oral carcinogenesis by naturally occurring xanthophylls, astaxanthin and canthaxanthin. Cancer Res 55(18):4059–4064

    CAS  PubMed  Google Scholar 

  156. Tanaka T, Kawamori T, Ohnishi M, Makita H, Mori H, Satoh K et al (1995) Suppression of azoxymethane-induced rat colon carcinogenesis by dietary administration of naturally occurring xanthophylls astaxanthin and canthaxanthin during the postinitiation phase. Carcinogenesis 16(12):2957–2963

    Article  CAS  PubMed  Google Scholar 

  157. Katsumura N, Okuno M, Onogi N, Moriwaki H, Muto Y, Kojima S (1996) Suppression of mouse skin papilloma by canthaxanthin and β-carotene in vivo: possibility of the regression of tumorigenesis by carotenoids without conversion to retinoic acid. Nutr Cancer 26(2):203–208

    Article  CAS  PubMed  Google Scholar 

  158. Tsushima M, Maoka T, Katsuyama M, Kozuka M, Matsuno T, Tokuda H et al (1995) Inhibitory effect of natural carotenoids on Epstein-Barr virus activation activity of a tumor promoter in Raji cells. A screening study for anti-tumor promoters. Biol Pharm Bull 18(2):227–233

    Article  CAS  PubMed  Google Scholar 

  159. Pasquet V, Morisset P, Ihammouine S, Chepied A, Aumailley L, Berard J-B et al (2011) Antiproliferative activity of violaxanthin isolated from bioguided fractionation of Dunaliella tertiolecta extracts. Mar Drugs 9(5):819–831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  160. Gyémánt N, Tanaka M, Molnár P, Deli J, Mándoky L, Molnár J (2006) Reversal of multidrug resistance of cancer cells in vitro: modification of drug resistance by selected carotenoids. Anticancer Res 26(1A):367–374

    PubMed  Google Scholar 

  161. Gijsbers L, van Eekelen HD, de Haan LH, Swier JM, Heijink NL, Kloet SK et al (2013) Induction of peroxisome proliferator-activated receptor γ (PPARγ)-mediated gene expression by tomato (Solanum lycopersicum L.) extracts. J Agric Food Chem 61(14):3419–3427

    Article  CAS  PubMed  Google Scholar 

  162. Haguet Q, Bonnet A, Bérard J-B, Goldberg J, Joguet N, Fleury A et al (2017) Antimelanoma activity of Heterocapsa triquetra pigments. Algal Res 25:207–215

    Article  Google Scholar 

  163. Maoka T, Tsushima M, Nishino H (2002) Isolation and characterization of dinochrome A and B, anti-carcinogenic active carotenoids from the fresh water red tide Peridinium bipes. Chem Pharm Bull 50(12):1630–1633

    Article  CAS  Google Scholar 

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  1. Advanced Pharmacognosy Research Laboratory, Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India

    Saikat Dewanjee, Sonjit Das, Swarnalata Joardar, Simanta Bhattacharjee & Pratik Chakraborty

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  1. Lahore College for Women University, Lahore, Pakistan

    Muhammad Zia-Ul-Haq

  2. Jadavpur University, Kolkata, India

    Saikat Dewanjee

  3. Shaheed Benazir Bhutto University, Sheringal Dir Upper, Pakistan

    Muhammad Riaz

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Dewanjee, S., Das, S., Joardar, S., Bhattacharjee, S., Chakraborty, P. (2021). Carotenoids as Anticancer Agents. In: Zia-Ul-Haq, M., Dewanjee, S., Riaz, M. (eds) Carotenoids: Structure and Function in the Human Body. Springer, Cham. https://doi.org/10.1007/978-3-030-46459-2_13

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