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Anticancer activity of lycopene in HT-29 colon cancer cell line

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Abstract

An inverse association between serum lycopene levels and the risk of cancers has been pointed out by many prospective and retrospective epidemiological studies which prompted more studies to be performed on animal models and cell cultures in order to test this hypothesis. The aim of the present study was to evaluate the antiproliferative and pro-apoptotic effect of lycopene on colon cancer HT-29 cell line. The effect of lycopene on the viability of HT-29 cell line was investigated using XTT assay. The levels of Bcl-2, cleaved caspase 3, BAX, cleaved PARP, and 8-oxo-dG in lycopene-treated HT-29 cells were measured using ELISA. Gamma-H2AX and cytochrome c expression was assessed semi-quantitatively using immunofluorescence staining. Lycopene at doses of 10 and 20 μM produced a significant antiproliferative effect on HT-29 cells compared to the control (p < 0.05). The IC50 value of lycopene in HT-29 cells was found to be 7.89 μM for 24 h. Lycopene (7.89 μM) significantly elevated cleaved caspase 3 (p < 0.01), BAX, and cleaved PARP, 8-oxo-dG levels (p < 0.05). The levels of γ-H2AX foci are significantly higher while the levels of cytochrome-c are lower (p < 0.05) in lycopene-treated HT-29 cells. These results indicate that lycopene has an antiproliferative apoptotic and genotoxic effect on HT-29 colon cancer cell line.

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All results obtained in this experiment were presented in Figs. 2, 3, 4, and 5 and Table 1.

References

  1. Kacan T, Nayir E, Altun A, Kilickap S, Babacan NA, Ataseven H, Kaya T. Antitumor activity of sorafenib on colorectal cancer. J Oncol Sci. 2016;2(2–3):53–7.

    Article  Google Scholar 

  2. Alhoshani N, Al-Johani N, Alkeraishan N, Alarifi S, Alkahtani S. Effect of lycopene as an adjuvant therapy with 5-florouracil in human colon cancer. Saudi J Biol Sci. 2022;29:103392. https://doi.org/10.1016/j.sjbs.2022.103392.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Siegel RL, Torre LA, Soerjomataram I, Hayes RB, Bray F, Weber TK, Jemal A. Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019;68(12):2179–85.

    Article  PubMed  Google Scholar 

  4. Dias MC, Vieiralves NFL, Gomes IFVG, Salvadori DMF, Rodrigues MAM, Barbisan LF. Effects of lycopene, synbiotic and their association on early biomarkers of rat colon carcinogenesis. Food Chem Toxicol. 2009;48:772–80. https://doi.org/10.1016/j.fct.2009.12.003.

    Article  CAS  PubMed  Google Scholar 

  5. Farinetti A, Zurlo V, Manenti A, Coppi F, Mattioli AV. Mediterranean diet and colorectal cancer: A systematic review. Nutrition. 2017;43–44:83–8. https://doi.org/10.1016/j.nut.2017.06.008.

    Article  CAS  PubMed  Google Scholar 

  6. Bieri JG, Brown ED, Smith JC. Determination of individual carotenoids in human plasma by high performance liquid chromatography. J Liq Chromatogr. 1985;8:473–84.

    Article  CAS  Google Scholar 

  7. Olson JA, Krinsky NI. Introduction: the colorful, fascinating world of the carotenoids: important physiologic modulators. J Fed Am Soc Exp Biol. 1995;9(15):1547–50.

    CAS  PubMed  Google Scholar 

  8. Cohen LA. A review of animal model studies of tomato carotenoids, lycopene, and cancer chemoprevention. Exp Biol Med (Maywood). 2002;227(10):864–8. https://doi.org/10.1177/153537020222701005.

    Article  CAS  PubMed  Google Scholar 

  9. Trejo-Solís C, Pedraza-Chaverrí J, Torres-Ramos M, Jiménez-Farfán D, Cruz Salgado A, Serrano-García N, Osorio-Rico L, Sotelo J. Multiple molecular and cellular mechanisms of action of lycopene in cancer inhibition. Evid Based Complement Alternat Med. 2013;2013:705121. https://doi.org/10.1155/2013/705121.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Joha Z, Yulak F, Öztürk A, Şahin B, Yildirim Ş. The anticancer effect of cannabinoid 2 agonist L-759,633 on C6 and SH-SY5Y cell lines. Turk J Sci Health. 2021;2(3):6–13.

    Google Scholar 

  11. Taskiran AS, Ergul M, Gunes H, Ozturk A, Sahin B, Ozdemir E. The effects of proton pump inhibitors (pantoprazole) on pentylenetetrazole-induced epileptic seizures in rats and neurotoxicity in the SH-SY5Y human neuroblastoma cell line. Cell Mol Neurobiol. 2021;41:173–83.

    Article  CAS  PubMed  Google Scholar 

  12. Ergul M, Bakar-Ates F. Investigation of molecular mechanisms underlying the antiproliferative effects of colchicine against PC3 prostate cancer cells. Toxicol Vitr. 2021;73:105138. https://doi.org/10.1016/j.tiv.2021.105138.

    Article  CAS  Google Scholar 

  13. Huang M, Lu JJ, Ding J. Natural products in cancer therapy: past, present and future. Nat Prod Bioprospect. 2021;11:5–13. https://doi.org/10.1007/s13659-020-00293-7.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gerster H. The potential role of lycopene for human health. J Am Coll Nutr. 1997;16:109–26.

    Article  CAS  PubMed  Google Scholar 

  15. Hoffmann I, Weisburger JH. International symposium on the role of lycopene and tomato products in disease prevention. Cancer Epidemiol Biomarkers Prev. 1997;6:643–5.

    CAS  PubMed  Google Scholar 

  16. Tang FY, Shih CJ, Cheng LH, Ho HJ, Chen HJ. Lycopene inhibits growth of human colon cancer cells via suppression of the Akt signaling pathway. Mol Nutr Food Res. 2008;52(6):646–54. https://doi.org/10.1002/mnfr.200700272.

    Article  CAS  PubMed  Google Scholar 

  17. Teodoro AJ, Oliveira FL, Martins NB, Maia Gde A, Martucci RB, Borojevic R. Effect of lycopene on cell viability and cell cycle progression in human cancer cell lines. Cancer Cell Int. 2012;12(1):36. https://doi.org/10.1186/1475-2867-12-36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Guil-Guerrero JL, Ramos-Bueno R, Rodríguez-García I, López-Sánchez C. Cytotoxicity screening of several tomato extracts. J Med Food. 2011;14(1–2):40–5. https://doi.org/10.1089/jmf.2010.0051.

    Article  PubMed  Google Scholar 

  19. Tang FY, Pai MH, Wang XD. Consumption of lycopene inhibits the growth and progression of colon cancer in a mouse xenograft model. J Agric Food Chem. 2011;59(16):9011–21. https://doi.org/10.1021/jf2017644.

    Article  CAS  PubMed  Google Scholar 

  20. Soares Nda C, Teodoro AJ, Oliveira FL, Santos CA, Takiya CM, Junior OS, Bianco M, Junior AP, Nasciutti LE, Ferreira LB, Gimba ER, Borojevic R. Influence of lycopene on cell viability, cell cycle, and apoptosis of human prostate cancer and benign hyperplastic cells. Nutr Cancer. 2013;65(7):1076–85. https://doi.org/10.1080/01635581.2013.812225.

    Article  CAS  PubMed  Google Scholar 

  21. Ivanov NI, Cowell SP, Brown P, Rennie PS, Guns ES, Cox ME. Lycopene differentially induces quiescence and apoptosis in androgen-responsive and -independent prostate cancer cell lines. Clin Nutr. 2007;26(2):252–63. https://doi.org/10.1016/j.clnu.2007.01.002.

    Article  CAS  PubMed  Google Scholar 

  22. Renju GL, Muraleedhara Kurup G, Bandugula VR. Effect of lycopene isolated from Chlorella marina on proliferation and apoptosis in human prostate cancer cell line PC-3. Tumour Biol. 2014;35(11):10747–58. https://doi.org/10.1007/s13277-014-2339-5.

    Article  CAS  PubMed  Google Scholar 

  23. Kanagaraj P, Vijayababu MR, Ravisankar B, Anbalagan J, Aruldhas MM, Arunakaran J. Effect of lycopene on insulin-like growth factor-I, IGF binding protein-3 and IGF type-I receptor in prostate cancer cells. J Cancer Res Clin Oncol. 2007;133(6):351–9. https://doi.org/10.1007/s00432-006-0177-6.

    Article  CAS  PubMed  Google Scholar 

  24. Takeshima M, Ono M, Higuchi T, Chen C, Hara T, Nakano S. Anti-proliferative and apoptosis-inducing activity of lycopene against three subtypes of human breast cancer cell lines. Cancer Sci. 2014;105(3):252–7. https://doi.org/10.1111/cas.12349.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gloria NF, Soares N, Brand C, Oliveira FL, Borojevic R, Teodoro AJ. Lycopene and beta-carotene induce cell-cycle arrest and apoptosis in human breast cancer cell lines. Anticancer Res. 2014;34(3):1377–86.

    CAS  PubMed  Google Scholar 

  26. Peng SJ, Li J, Zhou Y, Tuo M, Qin XX, Yu Q, Cheng H, Li YM. In vitro effects and mechanisms of lycopene in MCF-7 human breast cancer cells. Genet Mol Res. 2017. https://doi.org/10.4238/gmr16029434.

    Article  PubMed  Google Scholar 

  27. Wang R, Lu X, Yu R. Lycopene inhibits epithelial-mesenchymal transition and promotes apoptosis in oral cancer via PI3K/AKT/m-TOR signal pathway. Drug Des Dev Ther. 2020;14:2461–71. https://doi.org/10.2147/DDDT.S251614.

    Article  CAS  Google Scholar 

  28. Tao A, Wang X, Li C. Effect of lycopene on oral squamous cell carcinoma cell growth by inhibiting IGF1 pathway. Cancer Manag Res. 2021;13:723–32. https://doi.org/10.2147/CMAR.S283927.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Kim M, Kim SH, Lim JW, Kim H. Lycopene induces apoptosis by inhibiting nuclear translocation of β-catenin in gastric cancer cells. J Physiol Pharmacol. 2019. https://doi.org/10.26402/jpp.2019.4.11.

    Article  PubMed  Google Scholar 

  30. Han H, Lim JW, Kim H. Lycopene inhibits activation of epidermal growth factor receptor and expression of cyclooxygenase-2 in gastric cancer cells. Nutrients. 2019;11(9):2113. https://doi.org/10.3390/nu11092113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Salman H, Bergman M, Djaldetti M, Bessler H. Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed Pharmacother. 2007;61(6):366–9. https://doi.org/10.1016/j.biopha.2007.02.015.

    Article  CAS  PubMed  Google Scholar 

  32. Xu J, Li Y, Hu H. Effects of lycopene on ovarian cancer cell line SKOV3 in vitro: Suppressed proliferation and enhanced apoptosis. Mol Cell Probes. 2019;46:101419. https://doi.org/10.1016/j.mcp.2019.07.002.

    Article  CAS  PubMed  Google Scholar 

  33. Jeong Y, Lim JW, Kim H. Lycopene inhibits reactive oxygen species-mediated NF-κB signaling and induces apoptosis in pancreatic cancer cells. Nutrients. 2019;11(4):762. https://doi.org/10.3390/nu11040762.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Gupta P, Bansal MP, Koul A. Evaluating the effect of lycopene from Lycopersicum esculentum on apoptosis during NDEA induced hepatocarcinogenesis. Biochem Biophys Res Commun. 2013;434(3):479–85. https://doi.org/10.1016/j.bbrc.2013.03.099.

    Article  CAS  PubMed  Google Scholar 

  35. Cui L, Xu F, Wu K, Li L, Qiao T, Li Z, Chen T, Sun C. Anticancer effects and possible mechanisms of lycopene intervention on N-methylbenzylnitrosamine induced esophageal cancer in F344 rats based on PPARγ1. Eur J Pharmacol. 2020;881:173230. https://doi.org/10.1016/j.ejphar.2020.173230.

    Article  CAS  PubMed  Google Scholar 

  36. Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 2016;8(4):603–19. https://doi.org/10.18632/aging.100934.

    Article  CAS  PubMed  Google Scholar 

  37. Jeng PS, Inoue-Yamauchi A, Hsieh JJ, Cheng EH. BH3-dependent and independent activation of BAX and BAK in mitochondrial apoptosis. Curr Opin Physiol. 2018;3:71–81. https://doi.org/10.1016/j.cophys.2018.03.005.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Los M, Mozoluk M, Ferrari D, Stepczynska A, Stroh C, Renz A, Herceg Z, Wang ZQ, Schulze-Osthoff K. Activation and caspase-mediated inhibition of PARP: a molecular switch between fibroblast necrosis and apoptosis in death receptor signaling. Mol Biol Cell. 2002;13(3):978–88. https://doi.org/10.1091/mbc.01-05-0272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Ock CY, Kim EH, Choi DJ, Lee HJ, Hahm KB, Chung MH. 8-Hydroxydeoxyguanosine: not mere biomarker for oxidative stress, but remedy for oxidative stress-implicated gastrointestinal diseases. World J Gastroenterol. 2012;18(4):302–8. https://doi.org/10.3748/wjg.v18.i4.302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Podhorecka M, Skladanowski A, Bozko P. H2AX phosphorylation: its role in DNA damage response and cancer therapy. J Nucleic Acids. 2010;2010:920161. https://doi.org/10.4061/2010/920161.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgment

The authors would like to thank the Sivas Cumhuriyet University, School of Medicine, CUTFAM Research Center, Sivas, Turkey, for providing the necessary facilities to conduct this study.

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Correspondence to Ziad Joha.

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Ataseven, D., Öztürk, A., Özkaraca, M. et al. Anticancer activity of lycopene in HT-29 colon cancer cell line. Med Oncol 40, 127 (2023). https://doi.org/10.1007/s12032-023-02001-0

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