Advertisement

Piper betle Linn. in Cancer: Past, Present, and Future

  • Avinash Kundadka Kudva
  • Suresh Rao
  • Pratima Rao
  • Romith Periera
  • Ganesh Bhandari
  • Jaffey M. Mathew
  • K. Ashwini
  • Michael L. J. Pais
  • Mallappa Kumara Swamy
  • Manjeshwar Shrinath Baliga
Chapter

Abstract

Since time immemorial, Piper betle Linn. (betel vine or paan) has been an integral part of various traditional and folk medicines of Southeast Asian countries. The betel leaves are the most valued plant parts routinely used as chewing agent and known to prevent halitosis. Betel vine leaves possess numerous medicinal benefits, such as relieving indigestion, bronchitis, constipation, congestion, and cough. Betel vine leaves are mostly consumed as a part of betel quid, which consists of areca nut (Areca catechu Linn.), tobacco (Nicotiana tabacum Linn.), and slaked lime, a concoction with potent carcinogenic properties. Routine consumption of betel quid is associated with oral cancer, and scientific analyses have attributed that both tobacco and areca nut as carcinogenic, while slaked lime as a promoter of carcinogenesis. Conversely, betel vine leaves are devoid of carcinogenic effects and in turn known to possess cancer preventive effects that can negate carcinogens present in the quid. The aim of the chapter is to provide the information on betel vine’s cancer preventive effects and the mechanisms involved. Moreover, it also highlighted the various phytoconstituents that promote beneficial role of betel vine leaves against different cancers.

Keywords

Betel vine Paan Cancer Chemoprevention 

References

  1. Abdul Rahman A, Jamal AR, Harun R, Mohd Mokhtar N, Wan Ngah WZ (2014) Gamma-tocotrienol and hydroxy-chavicol synergistically inhibits growth and induces apoptosis of human glioma cells. BMC Compl Altern Med 14:213.  https://doi.org/10.1186/1472-6882-14-213
  2. Al-Sharif I, Remmal A, Aboussekhra A (2013) Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down-regulation. BMC Cancer 13:600.  https://doi.org/10.1186/1471-2407-13-600
  3. Ali SM, Khan AA, Ahmed I, Musaddiq M, Ahmed KS, Polasa H, Rao LV, Habibullah CM, Sechi LA, Ahmed N (2005) Antimicrobial activities of eugenol and Cinnamaldehyde against the human gastric pathogen Helicobacter pylori. Ann Clin Microbiol Antimicrob 4:20.  https://doi.org/10.1186/1476-0711-4-20 PubMedPubMedCentralCrossRefGoogle Scholar
  4. Amonkar AJ, Nagabhushan M, D’Souza AV, Bhide SV (1986) Hydroxychavicol: a new phenolic antimutagen from betel leaf. Food Chem Toxicol 24:1321–1324PubMedCrossRefPubMedCentralGoogle Scholar
  5. Amonkar AJ, Padma PR, Bhide SV (1989) Protective effect of hydroxychavicol, a phenolic component of betel leaf, against the tobacco-specific carcinogens. Mutat Res 210:249–253PubMedCrossRefPubMedCentralGoogle Scholar
  6. Annamalai SJK, Subashini SR, Priya JSR, Naik R (2016) Betel vine. In: Ambrose DC, Manickavasagan A, Naik R (eds) Leafy medicinal herbs: botany, chemistry, postharvest technology and uses. CAB eBooks CABI, New Delhi, pp 63–73.  https://doi.org/10.1079/9781780645599.0000
  7. Apalla Z, Nashan D, Weller RB, Castellsague X (2017) Skin cancer: epidemiology, disease burden, pathophysiology, diagnosis, and therapeutic approaches. Dermatol Ther 7:5–19CrossRefGoogle Scholar
  8. Arumugam G, Swamy MK, Sinniah UR (2016) Plectranthus amboinicus (Lour.) Spreng: botanical, phytochemical, pharmacological and nutritional significance. Molecules 21:369PubMedPubMedCentralCrossRefGoogle Scholar
  9. Azuine MA, Bhide SV (1992) Protective single/combined treatment with betel leaf and turmeric against methyl (acetoxymethyl) nitrosamine-induced hamster oral carcinogenesis. Int J Cancer 51:412–415PubMedPubMedCentralCrossRefGoogle Scholar
  10. Azuine MA, Amonkar AJ, Bhide SV (1991) Chemopreventive efficacy of betel leaf extract and its constituents on 7,12-dimethylbenz(a)anthracene induced carcinogenesis and their effect on drug detoxification system in mouse skin. Indian J Exp Biol 29:346–351PubMedPubMedCentralGoogle Scholar
  11. Bhattacharya S, Subramanian M, Roychowdhury S, Bauri AK, Kamat JP, Chattopadhyay S, Bandyopadhyay SK (2005) Radioprotective property of the ethanolic extract of Piper betle leaf. J Radiat Res 46:165–171PubMedPubMedCentralCrossRefGoogle Scholar
  12. Bhattacharya S, Chaudhuri SR, Chattopadhyay S, Bandyopadhyay SK (2007a) Healing properties of some Indian medicinal plants against indomethacin-induced gastric ulceration of rats. J Clin Biochem Nutr 41:106–114PubMedPubMedCentralCrossRefGoogle Scholar
  13. Bhattacharya S, Banerjee D, Bauri AK, Chattopadhyay S, Bandyopadhyay SK (2007b) Healing property of the Piper betle phenol, allylpyrocatechol against indomethacin-induced stomach ulceration and mechanism of action. World J Gastroenterol 13:3705–3713PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bhide SV, Shivapurkar NM, Gothoskar SV, Ranadive KJ (1979) Carcinogenicity of betel quid ingredients: feeding mice with aqueous extract and the polyphenol fraction of betel nut. Br J Cancer 40:922–926PubMedPubMedCentralCrossRefGoogle Scholar
  15. Bhide SV, Zariwala MB, Amonkar AJ, Azuine MA (1991a) Chemopreventive efficacy of a betel leaf extract against benzo[a]pyrene-induced fore stomach tumors in mice. J Ethnopharmacol 34:207–213PubMedCrossRefPubMedCentralGoogle Scholar
  16. Bhide SV, Padma PR, Amonkar AJ (1991b) Antimutagenic and anticarcinogenic effects of betel leaf extract against the tobacco-specific nitrosamine 4-(N-nitrosomethyllamino)-1-(3-pyridyl)-1-butanone (NNK). IARC Sci Publ 105:520–524Google Scholar
  17. Bhide SV, Azuine MA, Lahiri M, Telang NT (1994) Chemoprevention of mammary tumor virus-induced and chemical carcinogen-induced rodent mammary tumors by natural plant products. Breast Cancer Res Treat 30:233–242PubMedPubMedCentralCrossRefGoogle Scholar
  18. Boffetta P, Hecht S, Gray N, Gupta P, Straif K (2008) Smokeless tobacco and cancer. Lancet Oncol 9:667–675PubMedCrossRefPubMedCentralGoogle Scholar
  19. Bradford PT (2009) Skin cancer in skin of color. Dermatology nursing/Dermatology Nurses Association. Dermatol Nurs 21:170–178PubMedPubMedCentralGoogle Scholar
  20. Brunnemann KD, Hoffmann D (1992) Chemical composition of smokeless tobacco products. In: Smokeless tobacco or health. An international perspective, Smoking and Tobacco Control Monograph No. 2. National Cancer Institute, BethesdaGoogle Scholar
  21. Canniff JP, Harvey W (1981) The aetiology of oral submucous fibrosis: the stimulation of collagen synthesis by extracts of areca nut. Int J Oral Surg 10:163–167PubMedPubMedCentralGoogle Scholar
  22. Chakraborty JB, Mahato SK, Joshi K, Shinde V, Rakshit S, Biswas N, Choudhury Mukherjee I, Mandal L, Ganguly D, Chowdhury AA, Chaudhuri J, Paul K, Pal BC, Vinayagam J, Pal C, Manna A, Jaisankar P, Chaudhuri U, Konar A, Roy S, Bandyopadhyay S (2012) Hydroxychavicol, a Piper betle leaf component, induces apoptosis of CML cells through mitochondrial reactive oxygen species-dependent JNK and endothelial nitric oxide synthase activation and overrides imatinib resistance. Cancer Sci 103:88–99PubMedCrossRefPubMedCentralGoogle Scholar
  23. Chang MC, Uang BJ, Wu HL, Lee JJ, Hahn LJ, Jeng JH (2002) Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: roles of glutathione and reactive oxygen species. Br J Pharmacol 135:619–630PubMedPubMedCentralCrossRefGoogle Scholar
  24. Cheong SC, Vatanasapt P, Yi-Hsin Y, Zain RB, Kerr AR, Johnson NW (2017) Oral cancer in South East Asia: current status and future directions. Transl Res Oral Oncol 2:1–9.  https://doi.org/10.1177/2057178X1770292 CrossRefGoogle Scholar
  25. Choudhary D, Kale RK (2002) Antioxidant and non-toxic properties of Piper betle leaf extract: In vitro and in vivo studies. Phytother Res 16:461–466PubMedCrossRefPubMedCentralGoogle Scholar
  26. Crusz SM, Balkwill FR (2015) Inflammation and cancer: advances and new agents. Nat Rev Clin Oncol 12:584–596PubMedCrossRefPubMedCentralGoogle Scholar
  27. Das S, Parida R, Sriram Sandeep I, Nayak S, Mohanty S (2016) Biotechnological intervention in betel vine (Piper betle L.): A review on recent advances and future prospects. Asian Pac J Trop Med 9(10):938–946PubMedPubMedCentralCrossRefGoogle Scholar
  28. Dasgupta N, De B (2004) Antioxidant activity of Piper betle L. leaf extract in vitro. Food Chem 88:219–224CrossRefGoogle Scholar
  29. De Flora S, Ferguson LR (2005) Overview of mechanisms of cancer chemopreventive agents. Mutat Res 591:8–15PubMedCrossRefPubMedCentralGoogle Scholar
  30. Desai AG, Qazi GN, Ganju RK, El-Tamer M, Singh J, Saxena AK, Bedi YS, Taneja SC, Bhat HK (2008) Medicinal plants and cancer chemoprevention. Curr Drug Metab 9:581–591PubMedPubMedCentralCrossRefGoogle Scholar
  31. Devasagayam TP, Tilak JC, Boloor KK, Sane KS, Ghaskadbi SS, Lele RD (2004) Free radicals and antioxidants in human health: current status and future prospects. J Assoc Phys India 52:794–804Google Scholar
  32. Fazal F, Mane PP, Rai MP, Thilakchand KR, Bhat HP, Kamble PS, Palatty PL, Baliga MS (2014) The phytochemistry, traditional uses and pharmacology of Piper Betel. linn (Betel Leaf): a pan-asiatic medicinal plant. Chin J Integr Med 2014:1–11.  https://doi.org/10.1007/s11655-013-1334-1
  33. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM (2010) Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer 127(12):2893–2917CrossRefPubMedGoogle Scholar
  34. Fuchs-Tarlovsky V (2013) Role of antioxidants in cancer therapy. Nutrition 29:15–21PubMedPubMedCentralCrossRefGoogle Scholar
  35. Fujisawa S, Murakami Y (2016) Eugenol and Its role in chronic diseases. Adv Exp Med Biol 929:45–66Google Scholar
  36. Ganguly S, Mula S, Chattopadhyay S, Chatterjee M (2007) An ethanol extract of Piper betle Linn. mediates its anti-inflammatory activity via down regulation of nitric oxide. J Pharm Pharmacol 59:711–718PubMedCrossRefPubMedCentralGoogle Scholar
  37. Ghosh R, Nadiminty N, Fitzpatrick JE, Alworth WL, Slaga TJ, Kumar AP (2005) Eugenol causes melanoma growth suppression through inhibition of E2F1 transcriptional activity. J Biol Chem 280:5812–5819PubMedCrossRefPubMedCentralGoogle Scholar
  38. Guha P (2006) Betel leaf: the neglected green gold of India. J Hum Ecol 19:87–93CrossRefGoogle Scholar
  39. Gundala SR, Aneja R (2014) Piper betle leaf: a reservoir of potential xenohormetic nutraceuticals with cancer-fighting properties. Cancer Prev Res 7:477–486CrossRefGoogle Scholar
  40. Haas GP, Delongchamps N, Brawley OW, Wang CY, de la Roza G (2008) The worldwide epidemiology of prostate cancer: perspectives from autopsy studies. Can J Urol 15:3866–3871PubMedPubMedCentralGoogle Scholar
  41. Halliwell B (2007) Biochemistry of oxidative stress. Biochem Soc Trans 35:1147–1150PubMedCrossRefPubMedCentralGoogle Scholar
  42. IARC (2004) Betel-quid and areca nut chewing and some areca-nut derived nitrosamines. In: IARC Monographs vol. 85, International Agency for Research on Cancer, WHO, FranceGoogle Scholar
  43. Jaganathan SK, Mazumdar A, Mondhe D, Mandal M (2011) Apoptotic effect of eugenol in human colon cancer cell lines. Cell Biol Int 35:607–615PubMedCrossRefPubMedCentralGoogle Scholar
  44. Jagetia GC, Baliga MS (2004) The evaluation of nitric oxide scavenging activity of certain Indian medicinal plants in vitro: a preliminary study. J Med Food 7:343–348PubMedPubMedCentralCrossRefGoogle Scholar
  45. Jane NS, Deshmukh AP, Joshi MS (2014) Review of study of different diseases on betel vine plant and control measure. Int J Appl Innov Eng Manag 3:560–563Google Scholar
  46. Jang SH, Lim JW, Kim H (2009) Beta-carotene inhibits Helicobacter pylori induced expression of inducible nitric oxide synthase and cyclooxygenase-2 in human gastric epithelial AGS cells. J Physiol Pharmacol 60:131–137PubMedPubMedCentralGoogle Scholar
  47. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D (2011) Global cancer statistics. CA Cancer J Clin 61:69–90Google Scholar
  48. Jeng JH, Kuo ML, Hahn LJ, Kuo MY (1994) Genotoxic and non-genotoxic effects of betel quid ingredients on oral mucosal fibroblasts in vitro. J Dent Res 73:1043–1049CrossRefPubMedGoogle Scholar
  49. Jeng JH, Ho YS, Chan CP, Wang YJ, Hahn LJ, Lei D, Hsu CC, Chang MC (2000) Areca nut extract up-regulates prostaglandin production, cyclooxygenase-2 mRNA and protein expression of human oral keratinocytes. Carcinogenesis 21:1365–1370PubMedCrossRefPubMedCentralGoogle Scholar
  50. Jeng JH, Wang YJ, Chang WH, Wu HL, Li CH, Uang BJ, Kang JJ, Lee JJ, Hahn LJ, Lin BR, Chang MC (2004) Reactive oxygen species are crucial for hydroxychavicol toxicity toward KB epithelial cells. Cell Mol Life Sci 61:83–96PubMedCrossRefPubMedCentralGoogle Scholar
  51. Jin YT, Tsai ST, Wong TY, Chen FF, Chen RM (1996) Studies on promoting activity of Taiwan betel quid ingredients in hamster buccal pouch carcinogenesis. Eur J Cancer B Oral Oncol 32:343–346CrossRefGoogle Scholar
  52. Júnior PL, Câmara DA, Costa AS, Ruiz JL, Levy D, Azevedo RA, Pasqualoto KF, de Oliveira CF, de Melo TC, Pessoa ND, Fonseca PM, Pereira A, Araldi RP, Ferreira AK (2016) Apoptotic effect of eugenol envolves G2/M phase abrogation accompanied by mitochondrial damage and clastogenic effect on cancer cell in vitro. Phytomedicine 23:725–735PubMedCrossRefPubMedCentralGoogle Scholar
  53. Kassi E, Papoutsi Z, Pratsinis H, Aligiannis N, Manoussakis M, Moutsatsou P (2007) Ursolic acid: a naturally occurring triterpenoid, demonstrates anticancer activity on human prostate cancer cells. J Cancer Res Clin Oncol 133:493–500PubMedCrossRefPubMedCentralGoogle Scholar
  54. Kaur G, Athar M, Alam MS (2010) Eugenol precludes cutaneous chemical carcinogenesis in mouse by preventing oxidative stress and inflammation and by inducing apoptosis. Mol Carcinog 49:290–301PubMedGoogle Scholar
  55. Khan Z, Tönnies J, Müller S (2014) Smokeless tobacco and oral cancer in South Asia: a systematic review with meta-analysis. J Cancer Epidemiol 2014:394696.  https://doi.org/10.1155/2014/394696 CrossRefGoogle Scholar
  56. Kim SS, Oh OJ, Min HY, Park EJ, Kim Y, Park HJ, Nam Han Y, Lee SK (2003) Eugenol suppresses cyclooxygenase-2 expression in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Life Sci 73:337–348PubMedCrossRefPubMedCentralGoogle Scholar
  57. Kooti W, Servatyari K, Behzadifar M, Asadi-Samani M, Sadeghi F, Nouri B, Zare Marzouni H (2017) Effective medicinal Plant in Cancer Treatment, part 2: review study. J Evidence-Based Compl Altern Med 2017:1–14.  https://doi.org/10.1177/2156587217696927
  58. Kumar N, Misra P, Dube A, Bhattacharya S, Dikshit M, Ranade S (2010) Piper betle Linn. a maligned Pan-asiatic plant with an array of pharmacological activities and prospects for drug discovery. Curr Sci 99:922–932Google Scholar
  59. Lachenmayer A, Alsinet C, Chang CY, Liovit JM (2010) Molecular approaches to treatment of hepatocellular carcinoma. Dig Liver Dis 42:264–272CrossRefGoogle Scholar
  60. Lee CH, Lee JM, Wu DC, Hsu HK, Kao EL, Huang HL, Wang TN, Huang MC, Wu MT (2005) Independent and combined effects of alcohol intake, tobacco smoking and betel quid chewing on the risk of esophageal cancer in Taiwan. Int J Cancer 113:475–482CrossRefPubMedGoogle Scholar
  61. Lee YY, Hung SL, Pai SF, Lee YH, Yang SF (2007) Eugenol suppressed the expression of lipopolysaccharide-induced proinflammatory mediators in human macrophages. J Endod 33:698–702PubMedCrossRefPubMedCentralGoogle Scholar
  62. Lei D, Chan CP, Wang YJ, Wang TM, Lin BR, Huang CH, Lee JJ, Chen HM, Jeng JH, Chang MC (2003) Antioxidative and antiplatelet effects of aqueous inflorescence Piper betle extract. J Agric Food Chem 26:2083–2088CrossRefGoogle Scholar
  63. Manigauha A, Ali H, Maheshwari MU (2009) Antioxidant activity of ethanolic extract of Piper betle leaves. J Pharm Res 2:491–494Google Scholar
  64. Manikandan P, Murugan RS, Priyadarsini RV, Vinothini G, Nagini S (2010) Eugenol induces apoptosis and inhibits invasion and angiogenesis in a rat model of gastric carcinogenesis induced by MNNG. Life Sci 86:936–941CrossRefPubMedGoogle Scholar
  65. Mechali M, Mechali F, Laskey RA (1983) Tumor promoter TPA increases initiation of replication on DNA injected into Xenopus eggs. Cell 35:63–69PubMedCrossRefPubMedCentralGoogle Scholar
  66. Mohanty SK, Swamy MK, Sinniah UR, Anuradha M (2017) Leptadenia reticulata (Retz.) Wight & Arn. (Jivanti): botanical, agronomical, phytochemical, pharmacological, and biotechnological aspects. Molecules 22:1019.  https://doi.org/10.3390/molecules22061019 CrossRefGoogle Scholar
  67. Murakami A, Ali AM, Mat-Salleh K, Koshimizu K, Ohigashi H (2000) Screening for the in vitro anti-tumor-promoting activities of edible plants from Malaysia. Biosci Biotechnol Biochem 64:9–16PubMedCrossRefPubMedCentralGoogle Scholar
  68. Nagabhushan M, Amonkar AJ, D’Souza AV, Bhide SV (1987) Nonmutagenicity of betel leaf and its antimutagenic action against environmental mutagens. Neoplasma 34:159–167PubMedPubMedCentralGoogle Scholar
  69. Nagabhushan M, Amonkar AJ, D’Souza AV, Bhide SV (1989) Hydroxychavicol: a new anti-nitrosating phenolic compound from betel leaf. Mutagenesis 4:200–204CrossRefPubMedGoogle Scholar
  70. Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477CrossRefPubMedGoogle Scholar
  71. Ng PL, Rajab NF, Then SM, Mohd Yusof YA, Wan Ngah WZ, Pin KY, Looi ML (2014) Piper betle leaf extract enhances the cytotoxicity effect of 5-fluorouracil in inhibiting the growth of HT29 and HCT116 colon cancer cells. J Zhejiang Univ Sci B 15:692–700PubMedPubMedCentralCrossRefGoogle Scholar
  72. Padma PR, Lalitha VS, Amonkar AJ, Bhide SV (1989a) Anticarcinogenic effect of betel leaf extract against tobacco carcinogens. Cancer Lett 45:195–202PubMedPubMedCentralCrossRefGoogle Scholar
  73. Padma PR, Amonkar AJ, Bhide SV (1989b) Antimutagenic effects of betel leaf extract against the mutagenicity of two tobacco-specific N-nitrosamines. Mutagenesis 4:154–156PubMedCrossRefPubMedCentralGoogle Scholar
  74. Pal D, Banerjee S, Mukherjee S, Roy A, Panda CK, Das S (2010) Eugenol restricts DMBA croton oil induced skin carcinogenesis in mice: downregulation of c-Myc and H-ras, and activation of p53 dependent apoptotic pathway. J Dermatol Sci 59:31–39PubMedCrossRefPubMedCentralGoogle Scholar
  75. Paranjpe R, Gundala SR, Lakshminarayana N, Sagwal A, Asif G, Pandey A, Aneja R (2013) Piper betel leaf extract: anticancer benefits and bioguided fractionation to identify active principles for prostate cancer management. Carcinogenesis 34:1558–1566PubMedPubMedCentralCrossRefGoogle Scholar
  76. Percival M (1997) Phytonutrients and detoxification. Clin Nutr Insights 5:1–3Google Scholar
  77. Pisano M, Pagnan G, Loi M, Mura ME, Tilocca MG, Palmieri G, Fabbri D, Dettori MA, Delogu G, Ponzoni M, Rozzo C (2007) Antiproliferative and pro-apoptotic activity of eugenol-related biphenyls on malignant melanoma cells. Mol Cancer 6:8.  https://doi.org/10.1186/1476-4598-6-8 PubMedPubMedCentralCrossRefGoogle Scholar
  78. Rai MP, Thilakchand KR, Palatty PL, Rao P, Rao S, Bhat HP, Baliga MS (2011) Piper betel Linn (betel vine), the maligned Southeast Asian medicinal plant possesses cancer preventive effects: time to reconsider the wronged opinion. Asian Pac J Cancer Prev 12:2149–2156Google Scholar
  79. Rakshit S, Mandal L, Pal BC, Bagchi J, Biswas N, Chaudhuri J, Chowdhury AA, Manna A, Chaudhuri U, Konar A, Mukherjee T, Jaisankar P, Bandyopadhyay S (2010) Involvement of ROS in chlorogenic acid-induced apoptosis of Bcr-Abl(+) CML cells. Biochem Pharmacol 80:1662–1675PubMedCrossRefPubMedCentralGoogle Scholar
  80. Rao AR (1984) Modifying influences of betel quid ingredients on B(a)P-induced carcinogenesis in the buccal pouch of hamster. Int J Cancer 15:581–586CrossRefGoogle Scholar
  81. Rao AR, Sinha A, Selvan RS (1985) Inhibitory action of Piper betle on the initiation of 7,12-dimethyl benz[a]anthracene-induced mammary carcinogenesis in rats. Cancer Lett 26:207–214PubMedPubMedCentralCrossRefGoogle Scholar
  82. Rathee JS, Patro BS, Mula S, Gamre S, Chattopadhyay S (2006) Antioxidant activity of Piper betel leaf extract and its constituents. J Agric Food Chem 54:9046–9054PubMedPubMedCentralCrossRefGoogle Scholar
  83. Reuter S, Gupta SC, Chaturvedi MM, Aggarwal BB (2010) Oxidative stress, inflammation, and cancer: how are they linked. Free Radic Biol Med 49:1603–1616PubMedPubMedCentralCrossRefGoogle Scholar
  84. Rintu D, Shinjini M, Kaustab M, Pramathadhip P, Umesh PS, Banerjee ER (2015) Anti-oxidant and anti-inflammatory activities of different varieties of piper leaf extracts (Piper Betle L.). J Nutr Food Sci 5:415.  https://doi.org/10.4172/2155-9600.1000415
  85. Sarkar D, Saha P, Gamre S, Bhattacharjee S, Hariharan C, Ganguly S, Sen R, Mandal G, Chattopadhyay S, Majumdar S, Chatterjee M (2008) Anti-inflammatory effect of allylpyrocatechol in LPS-induced macrophages is mediated by suppression of iNOS and COX-2 via the NF-kappaB pathway. Int Immunopharmacol 8:1264–1271PubMedPubMedCentralCrossRefGoogle Scholar
  86. Sarkar A, Bhattacharjee S, Mandal DP (2015) Induction of apoptosis by eugenol and capsaicin in human gastric cancer AGS cells-elucidating the role of p53. Asian Pac J Cancer Prev 16:6753–6759PubMedCrossRefPubMedCentralGoogle Scholar
  87. Satyavati GV, Raina MK, Sharma M (1987) Medicinal plants of India, vol 1. Indian Council of Medical Research, New DelhiGoogle Scholar
  88. Shah GA, Shah TI, Telang S (2016) Anti-proliferative efficacy of Piper betle leaf extracts against B16F10 melanoma in an in-vivo experimental model. World J Pharm Pharm Sci 5:835–843Google Scholar
  89. Shao JW, Dai YC, Xue JP, Wang JC, Lin FP, Guo YH (2011) In vitro and in vivo anticancer activity evaluation of ursolic acid derivatives. Eur J Med Chem 46:2652–2661PubMedCrossRefPubMedCentralGoogle Scholar
  90. Sharma S, Khan IA, Ali I, Ali F, Kumar M, Kumar A, Johri RK, Abdullah ST, Bani S, Pandey A, Suri KA, Gupta BD, Satti NK, Dutt P, Qazi GN (2009) Evaluation of the antimicrobial, antioxidant, and anti-inflammatory activities of hydroxychavicol for its potential use as an oral care agent. Antimicrob Agents Chemother 53:216–222PubMedCrossRefPubMedCentralGoogle Scholar
  91. Shirname LP, Menon MM, Nair J, Bhide SV (1983) Correlation of mutagenicity and tumorigenicity of betel quid and its ingredients. Nutr Cancer 5:87–91PubMedCrossRefPubMedCentralGoogle Scholar
  92. Sukumaran K, Kuttan R (1995) Inhibition of tobacco-induced mutagenesis by eugenol and plant extracts. Mutat Res 343:25–30PubMedPubMedCentralCrossRefGoogle Scholar
  93. Sukumaran K, Unnikrishnan MC, Kuttan R (1994) Inhibition of tumour promotion in mice by eugenol. Indian J Physiol Pharmacol 38:306–308PubMedPubMedCentralGoogle Scholar
  94. Sundqvist K, Liu Y, Nair J, Bartsch H, Arvidson K, Grafstrom RC (1989) Cytotoxic and genotoxic effects of areca nut-related compounds in cultured human buccal epithelial cells. Cancer Res 49:5294–5298PubMedPubMedCentralGoogle Scholar
  95. Swamy MK, Sinniah UR (2016) Patchouli (Pogostemon cablin Benth.): botany, agrotechnology and biotechnological aspects. Ind Crop Prod 87:161–176CrossRefGoogle Scholar
  96. Taneja SC, Qazi GN (2007) Bioactive molecules in medicinal plants: a perspective in their therapeutic action. In: Chorghade MS (ed) Drug discovery and development. Wiley, Hoboken, pp 1–50Google Scholar
  97. Tariq A, Sadia S, Pan K, Ullah I, Mussarat S, Sun F, Abiodun OO, Batbaatar A, Li Z, Song D, Xiong Q (2017) A systematic review on ethnomedicines of anti-cancer plants. Phytother Res 31:202–264PubMedCrossRefPubMedCentralGoogle Scholar
  98. Thomas SJ, MacLennan R (1992) Slaked lime and betel nut cancer in Papua New Guinea. Lancet 340:577–578PubMedCrossRefPubMedCentralGoogle Scholar
  99. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108PubMedPubMedCentralCrossRefGoogle Scholar
  100. Trivedi AH, Patel RK, Rawal UM, Rawal UM, Adhvaryu SG, Balar DB (1994) Evaluation of chemopreventive effects of betel leaf on the genotoxicity of pan masala. Neoplasma 41:177–181PubMedPubMedCentralGoogle Scholar
  101. Umezawa K, Fujie S, Sawamura M, Matsushima T, Katoh Y, Tanaka M, Takayama S (1981) Morphological transformation, sister chromatid exchange and mutagenesis assay of betel constituents. Toxicol Lett 8:17–22PubMedCrossRefPubMedCentralGoogle Scholar
  102. Wagh V, Mishra P, Thakkar A, Shinde V, Sharma S, Padigaru M, Joshi K (2011) Antitumor activity of NPB001-05, an orally active inhibitor of Bcr-Abl tyrosine kinase. Front Biosci 3:131349–131364Google Scholar
  103. Wang CK, Peng CH (1996) The mutagenicities of alkaloids and N-nitrosoguvacoline from betel quid. Mutat Res 360:165–171PubMedPubMedCentralCrossRefGoogle Scholar
  104. Wang LY, You SL, Lu SN, Ho HC, Wu MH, Sun CA, Yang HI, Chien-Jen C (2003) Risk of hepatocellular carcinoma and habits of alcohol drinking, betel quid chewing and cigarette smoking: a cohort of 2416 HBsAg-seropositive and 9421 HBsAg-seronegative male residents in Taiwan. Cancer Causes Control 14:241–250PubMedCrossRefPubMedCentralGoogle Scholar
  105. Waris G, Ahsan H (2006) Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog 5:14PubMedPubMedCentralCrossRefGoogle Scholar
  106. Warnakulasuriya S (2009) Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 45:309–316PubMedCrossRefPubMedCentralGoogle Scholar
  107. Warrier PK, Nambair VPK, Ramankutty C (1995) Indian medicinal plants: a compendium of 500 species. Arya Vaidya Sala, Kottakal. Orient Longman, IndiaGoogle Scholar
  108. Weisburger JH (2001) Antimutagenesis and anticarcinogenesis, from the past to the future. Mutat Res 480–481:23–35PubMedCrossRefPubMedCentralGoogle Scholar
  109. Yamai H, Sawada N, Yoshida T, Seike J, Takizawa H, Kenzaki K, Miyoshi T, Kondo K, Bando Y, Ohnishi Y, Tangoku A (2009) Triterpenes augment the inhibitory effects of anticancer drugs on growth of human esophageal carcinoma cells in vitro and suppress experimental metastasis in vivo. Int J Cancer 125:952–960PubMedCrossRefPubMedCentralGoogle Scholar
  110. Yokota H, Hoshino J, Yuasa A (1986) Suppressed mutagenicity of benzo[a]pyrene by the liver S9 fraction and microsomes from eugenol-treated rats. Mutat Res 172:231–236PubMedCrossRefPubMedCentralGoogle Scholar
  111. Young SC, Wang CJ, Lin JJ, Peng PL, Hsu JL, Chou FP (2007) Protection effect of Piper betel leaf extract against carbon tetrachloride-induced liver fibrosis in rats. Arch Toxicol 8:45–55CrossRefGoogle Scholar
  112. Yu YX, Gu ZL, Yin JL, Chou WH, Kwok CY, Qin ZH, Liang ZQ (2010) Ursolic acid induces human hepatoma cell line SMMC-7721 apoptosis via p53-dependent pathway. Chin Med J 123:1915–1923PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Avinash Kundadka Kudva
    • 1
  • Suresh Rao
    • 2
  • Pratima Rao
    • 2
  • Romith Periera
    • 2
  • Ganesh Bhandari
    • 2
  • Jaffey M. Mathew
    • 2
  • K. Ashwini
    • 1
  • Michael L. J. Pais
    • 2
  • Mallappa Kumara Swamy
    • 3
  • Manjeshwar Shrinath Baliga
    • 2
  1. 1.Department of BiochemistryMangalore UniversityMangaloreIndia
  2. 2.Mangalore Institute of Oncology, PumpwellMangaloreIndia
  3. 3.Department of Crop Science, Faculty of AgricultureUniversiti Putra MalaysiaSerdangMalaysia

Personalised recommendations