Apoptosis Effects of Oxalis Corniculata L. Extract on Human MCF-7 Breast Cancer Cell Line
DOI:
https://doi.org/10.31661/gmj.v11i.2484Keywords:
Apoptosis, MCF-7, Breast Cancer, Oxalis Corniculate, Bax, p53, Bcl-2Abstract
Background: Recently, the non-toxic properties of natural plant products have gained more focus as anticancer agents. Therefore, this study aimed to assess the apoptosis effects of the ethanolic extract of Oxalis corniculata on the MCF-7 breast cancer cell line. Materials and Methods: In this experimental study, aerial parts of O. corniculata were collected in Lahijan city (Iran), and after confirmation, they were dried and extracted with ethanol for 24 h. Then, the total phenolic and flavonoid contents of the extract were measured. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay was used to measure the antioxidant properties of the extract. Selected cell lines (MCF-7 and human dermal fibroblast) were cultured in 6-wells dishes (1×106 cells/well). After 72 h of treating the extract, cytotoxicity was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The expression of apoptotic genes (such as p53, bcl-2, bax, and CD95) was studied by real-time polymerase chain reaction (PCR). Results: The extract's total phenolic content was 31.30±02 µg of gallic acid equivalents/mg of dry extract, and the total flavonoid content was 49.61±04 µg of quercetin as equivalents/mg of extract. The antioxidant activity of O. corniculata was measured at the dose of 619.2 µg/µl, indicating that it decreases cancer cell viability and enhances apoptosis. Within the half maximal inhibitory concentrations, real-time PCR revealed substantial increases in p53 (P<0.001), CD95 (P<0.05), and bcl-2 expression (P<0.05) in MCF-7 cells treated with O. corniculata. Conclusion: This study suggests that O. corniculata may cause apoptosis by oxidative stress in cancer cells
References
Chen C, Kong AN. Dietary cancer-chemopreventive compounds: from signaling and gene expression to pharmacological effects. Trends Pharmacol Sci. 2005;26(6):318-26. https://doi.org/10.1016/j.tips.2005.04.004PMid:15925707 Nafissi N, Khayamzadeh M, Zeinali Z, Pazooki D, Hosseini M, Akbari ME. Epidemiology and histopathology of breast cancer in Iran versus other Middle Eastern countries. Middle East J Cancer. 2018;9(3):243-51. Kathiriya AK, Das K, Kumar E, Mathai K. Evaluation of Antitumor and Antioxidant Activity of Oxalis Corniculata Linn. against Ehrlich Ascites Carcinoma on Mice. Int J Cancer Manag. 2010;3(4):e80710. Abdelghffar EA, El-Nashar HA, Al-Mohammadi AG, Eldahshan OA. Orange fruit (Citrus sinensis) peel extract attenuates chemotherapy-induced toxicity in male rats. Food Funct. 2021;12(19):9443-55. https://doi.org/10.1039/D1FO01905HPMid:34606555 Liu Y-Q, Wang X-L, He D-H, Cheng Y-X. Protection against chemotherapy-and radiotherapy-induced side effects: A review based on the mechanisms and therapeutic opportunities of phytochemicals. Phytomedicine. 2021;80:153402. https://doi.org/10.1016/j.phymed.2020.153402PMid:33203590 Danial NN, Korsmeyer SJ. Cell death: critical control points. Cell. 2004;116(2):205-19. https://doi.org/10.1016/S0092-8674(04)00046-7 Hassan M, Watari H, AbuAlmaaty A, Ohba Y, Sakuragi N. Apoptosis and molecular targeting therapy in cancer. Biomed Res Int. 2014;2014:150845. https://doi.org/10.1155/2014/150845PMid:25013758 PMCid:PMC4075070 Chiu LC-M, Ho T-S, Wong EY-L, Ooi VE. Ethyl acetate extract of Patrinia scabiosaefolia downregulates anti-apoptotic Bcl-2/Bcl-XL expression, and induces apoptosis in human breast carcinoma MCF-7 cells independent of caspase-9 activation. J. Ethnopharmacol. 2006;105(1-2):263-8. https://doi.org/10.1016/j.jep.2005.11.007PMid:16361073 Pilane M, Bagla V, Mokgotho M, Mbazima V, Matsebatlela T, Ncube I, et al. Free radical scavenging activity: antiproliferative and proteomics analyses of the differential expression of apoptotic proteins in MCF-7 cells treated with acetone leaf extract of Diospyros lycioides (Ebenaceae). Evid Based Complement Alternat Med. 2015;2015:534808. https://doi.org/10.1155/2015/534808PMid:26457109 PMCid:PMC4589632 Liu T, Xiong J, Yi S, Zhang H, Zhou S, Gu L, et al. FKBP12 enhances sensitivity to chemotherapy-induced cancer cell apoptosis by inhibiting MDM2. Oncogene. 2017;36(12):1678-86. https://doi.org/10.1038/onc.2016.331PMid:27617579 PMCid:PMC5378873 Chang H, Li C, Huo K, Wang Q, Lu L, Zhang Q, et al. Luteolin prevents H2O2-induced apoptosis in H9C2 cells through modulating Akt-P53/Mdm2 signaling pathway. Biomed Res Int. 2016;2016. https://doi.org/10.1155/2016/5125836PMid:27525270 PMCid:PMC4976196 Liu T, Wu Z, He Y, Xiao Y, Xia C. Single and dual target inhibitors based on Bcl-2: Promising anti-tumor agents for cancer therapy. Eur J Med Chem. 2020;201:112446. https://doi.org/10.1016/j.ejmech.2020.112446PMid:32563811 Suvarna V, Singh V, Murahari M. Current overview on the clinical update of Bcl-2 anti-apoptotic inhibitors for cancer therapy. Eur J Pharmacol. 2019;862:172655. https://doi.org/10.1016/j.ejphar.2019.172655PMid:31494078 Kazemi N, Shahrestani SB. Effect of Saffron Extract on Expression of Bax and Bcl-2 Genes in Gastric Adenocarcinoma Cell Line (AGS). Gene, Cell and Tissue. 2018;5(3): e63608. https://doi.org/10.5812/gct.63608 Opferman JT, Kothari A. Anti-apoptotic BCL-2 family members in development. Cell Death Differ. 2018;25(1):37-45. https://doi.org/10.1038/cdd.2017.170PMid:29099482 PMCid:PMC5729530 Warren CF, Wong-Brown MW, Bowden NA. BCL-2 family isoforms in apoptosis and cancer. Cell Death Dis. 2019;10(3):1-12. https://doi.org/10.1038/s41419-019-1407-6PMid:30792387 PMCid:PMC6384907 Harandi H, Falahati-Pour SK, Mahmoodi M, Faramarz S, Maleki H, Nasab FB, et al. Nanoliposomal formulation of pistachio hull extract: preparation, characterization and anticancer evaluation through Bax/Bcl2 modulation. Mol Biol Rep. 2022;49(4):2735-43. https://doi.org/10.1007/s11033-021-07083-5PMid:35037194 Knight T, Luedtke D, Edwards H, Taub JW, Ge Y. A delicate balance-The BCL-2 family and its role in apoptosis, oncogenesis, and cancer therapeutics. Biochem. Pharmacol. 2019;162:250-61. https://doi.org/10.1016/j.bcp.2019.01.015PMid:30668936 Jemal A, Ward EM, Johnson CJ, Cronin KA, Ma J, Ryerson AB, et al. Annual report to the nation on the status of cancer, 1975-2014, featuring survival. J Natl Cancer Inst. 2017;109(9):djx030. https://doi.org/10.1093/jnci/djx030 Liao S, Hu X, Liu Z, Lin Y, Liang R, Zhang Y, et al. Synergistic action of microwave induced mild hyperthermia and paclitaxel in inducing apoptosis in the human breast cancer cell line MCF 7. Oncol Lett. 2019;17(1):603-15. https://doi.org/10.3892/ol.2018.9629 Luo Y, Mok TS, Lin X, Zhang W, Cui Y, Guo J, et al. SWATH-based proteomics identified carbonic anhydrase 2 as a potential diagnosis biomarker for nasopharyngeal carcinoma. Sci Rep. 2017;7(1):1-11. https://doi.org/10.1038/srep41191PMid:28117408 PMCid:PMC5259699 Tuasha N, Petros B, Asfaw Z. Plants used as anticancer agents in the Ethiopian traditional medical practices: a systematic review. Evid Based Complement Alternat Med. 2018;2018 :6274021. https://doi.org/10.1155/2018/6274021PMid:30402131 PMCid:PMC6192134 Xiang L-P, Wang A, Ye J-H, Zheng X-Q, Polito CA, Lu J-L, et al. Suppressive effects of tea catechins on breast cancer. Nutrients. 2016;8(8):458. https://doi.org/10.3390/nu8080458PMid:27483305 PMCid:PMC4997373 Gajendran B, Durai P, Varier KM, Chinnasamy A. A novel phytosterol isolated from Datura inoxia, RinoxiaB is a potential cure colon cancer agent by targeting BAX/Bcl2 pathway. Bioorg Med Chem. 2020;28(2):115242. https://doi.org/10.1016/j.bmc.2019.115242PMid:31866271 Ghahremaninejad F, Gholamian F. A new record (Oxalis articulata) from Iran. Iran J Bot. 2006;12(1):55-6. Hosseini H, Handali S, Parishani M, Ghezelbash G, Ameri A. A Comparative Study of Antibacterial Effects of Aqueous Extract of Oxalis corniculata L. with Antibacterial Effects of Common Atibiotics in Staphylococcus aureous and E. coli Infections. J Med Plants. 2010;9(33):103-7. Madhava Chetty K, Sivaji K, Tulasi Rao K. Flowering plants of Chittoor district, Andhra pradesh, India. Tirupati: Students Offset Printers; 2008. p. 61. Hsieh P-C, Mau J-L, Huang S-H. Antimicrobial effect of various combinations of plant extracts. Food Microbiol. 2001;18(1):35-43. https://doi.org/10.1006/fmic.2000.0376 Rayburn ER, Ezell SJ, Zhang R. Anti-inflammatory agents for cancer therapy. Mol Cell Pharmacol. 2009;1(1):29. https://doi.org/10.4255/mcpharmacol.09.05PMid:20333321 PMCid:PMC2843097 Salahuddin H, Mansoor Q, Batool R, Farooqi AA, Mahmood T, Ismail M. Anticancer activity of Cynodon dactylon and Oxalis corniculata on Hep2 cell line. Cell Mol Biol. (Noisy-le-grand). 2016;62(5):60-3. Hamidi M, Ghasemi S, Bavafa Bighdilou B, Eghbali Koohi D. Evaluation of antioxidant, antibacterial and cytotoxic activity of methanol extract from leaves and fruits of Iranian squirting cucumber (Ecballium elaterium (L.) A. Rich). Res J Pharmacogn. 2020;7(1):23-9. Ghasemi S, Koohi DE, Emmamzadehhashemi MSB, Khamas SS, Moazen M, Hashemi AK, et al. Investigation of phenolic compounds and antioxidant activity of leaves extracts from seventeen cultivars of Iranian olive (Olea europaea L.). J Food Sci Technol. 2018;55(11):4600-7. https://doi.org/10.1007/s13197-018-3398-1PMid:30333656 PMCid:PMC6170347 Saeidnia S, Gohari AR. Pharmacognosy and molecular pharmacognosy in practice: A laboratory desk reference of pharmacognosy for researchers and students. Lap Lambert Academic Publ; 2012. Yousefbeyk F, Gohari AR, Hashemighahderijani Z, Ostad SN, Sourmaghi MHS, Amini M, et al. Bioactive terpenoids and flavonoids from Daucus littoralis Smith subsp. hyrcanicus Rech. f, an endemic species of Iran. Daru. 2014;22(1):1-6. https://doi.org/10.1186/2008-2231-22-12PMid:24397958 PMCid:PMC4029373 Borah A, Yadav R, Unni B. Evaluation of antioxidant activity of different solvent extracts of Oxalis corniculata L. J Pharm Res. 2012;5(1):91-3. Khyadea MS, Kambleb SP, Wamanc MB, Padwala AD, Jadhava SD. Chemical profiling and free radical scavenging potential of Oxalis corniculata. Explorer. 2016;1(1):88. Burgos-Moron E, Perez-Guerrero C, Lopez-Lazaro M, Calderon-Montano J. A review on the dietary flavonoid kaempferol. Mini Rev Med Chem. 2011;11(4):298-344. https://doi.org/10.2174/138955711795305335PMid:21428901 Otake Y, Walle T. Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9. Drug Metab Dispos. 2002;30(2):103-5. https://doi.org/10.1124/dmd.30.2.103PMid:11792676 Lu X, Qian C-N, Mu Y-G, Li N-W, Li S, Zhang H-B, et al. Serum CCL2 and serum TNF-α-Two new biomarkers predict bone invasion, post-treatment distant metastasis and poor overall survival in nasopharyngeal carcinoma. Eur J Cancer. 2011;47(3):339-46. https://doi.org/10.1016/j.ejca.2010.09.025PMid:20951575 Ahmed S, Jubair A, Hossain MA, Hossain MM, Azam MS, Biswas M. Free radical-scavenging capacity and HPLC-DAD screening of phenolic compounds from pulp and seed of Syzygium claviflorum fruit. J Agric Res Food Res. 2021;6:100203. https://doi.org/10.1016/j.jafr.2021.100203 Hosseini MM, Karimi A, Behroozaghdam M, Javidi MA, Ghiasvand S, Bereimipour A, et al. Cytotoxic and apoptogenic effects of cyanidin-3-glucoside on the glioblastoma cell line. World Neurosurg. 2017;108:94-100. https://doi.org/10.1016/j.wneu.2017.08.133PMid:28867321 Batra P, Sharma AK. Anticancer potential of flavonoids: recent trends and future perspectives. 3 Biotech. 2013;3(6):439-59. https://doi.org/10.1007/s13205-013-0117-5PMid:28324424 PMCid:PMC3824783 Ravishankar D, Rajora AK, Greco F, Osborn HM. Flavonoids as prospective compounds for anticancer therapy. Int J Biochem Cell Biol. 2013;45(12):2821-31. https://doi.org/10.1016/j.biocel.2013.10.004PMid:24128857 Gomes CA, Girão da Cruz T, Andrade JL, Milhazes N, Borges F, Marques MPM. Anticancer activity of phenolic acids of natural or synthetic origin: a structure− activity study. J Med Chem. 2003;46(25):5395-401. https://doi.org/10.1021/jm030956vPMid:14640548 Azmi AS, Bhat SH, Hanif S, Hadi S. Plant polyphenols mobilize endogenous copper in human peripheral lymphocytes leading to oxidative DNA breakage: a putative mechanism for anticancer properties. FEBS Lett. 2006;580(2):533-8. https://doi.org/10.1016/j.febslet.2005.12.059PMid:16412432 Sakat S, Juvekar AR, Gambhire MN. In vitro antioxidant and anti-inflammatory activity of methanol extract of Oxalis corniculata Linn. Int J Pharm Pharm Sci. 2010;2(1):146-55. Saeed N, Khan MR, Shabbir M. Antioxidant activity, total phenolic and total flavonoid contents of whole plant extracts Torilis leptophylla L. BMC Complement Altern Med. 2012;12(1):1-12. https://doi.org/10.1186/1472-6882-12-221PMid:23153304 PMCid:PMC3524761 Al-Dabbagh B, Elhaty IA, Al Sakkaf R, El-Awady R, Ashraf SS, Amin A. Antioxidant and anticancer activities of Trigonella foenum-graecum, Cassia acutifolia and Rhazya stricta. BMC Complement Altern Med. 2018;18(1):1-12. https://doi.org/10.1186/s12906-018-2285-7PMid:30134897 PMCid:PMC6103858 Dai J, Mumper RJ. Plant phenolics: extraction, analysis and their antioxidant and anticancer properties. Molecules. 2010;15(10):7313-52. https://doi.org/10.3390/molecules15107313PMid:20966876 PMCid:PMC6259146 Tauchen J, Bortl L, Huml L, Miksatkova P, Doskocil I, Marsik P, et al. Phenolic composition, antioxidant and anti-proliferative activities of edible and medicinal plants from the Peruvian Amazon. Rev Bras Farmacogn. 2016;26(6):728-37. https://doi.org/10.1016/j.bjp.2016.03.016 Nguyen NH, Ta QTH, Pham QT, Luong TNH, Phung VT, Duong T-H, et al. Anticancer activity of novel plant extracts and compounds from Adenosma bracteosum (bonati) in human lung and liver cancer cells. Molecules. 2020;25(12):2912. https://doi.org/10.3390/molecules25122912PMid:32599892 PMCid:PMC7356985 Al-Rimawi F, Rishmawi S, Ariqat SH, Khalid MF, Warad I, Salah Z. Anticancer activity, antioxidant activity, and phenolic and flavonoids content of wild Tragopogon porrifolius plant extracts. Evid Based Complement Alternat Med. 2016;2016. https://doi.org/10.1155/2016/9612490PMid:27999608 PMCid:PMC5143780 Bai L, Zhu W-G. p53: structure, function and therapeutic applications. J Cancer Mol. 2006;2(4):141-53. Jangholi E, Sharifi ZN, Hoseinian M, Zarrindast MR, Rahimi HR, Mowla A, et al. Verapamil Inhibits Mitochondria-Induced Reactive Oxygen Species and Dependent Apoptosis Pathways in Cerebral Transient Global Ischemia/Reperfusion. Oxid Med Cell Longev. 2020;2020:5872645. https://doi.org/10.1155/2020/5872645PMid:33133347 PMCid:PMC7591985 Storz P. Reactive oxygen species in tumor progression. Front Biosci. 2005;10(1-3):1881-96. https://doi.org/10.2741/1667PMid:15769673 Pelicano H, Carney D, Huang P. ROS stress in cancer cells and therapeutic implications. Drug Resist Updat. 2004;7(2):97-110. https://doi.org/10.1016/j.drup.2004.01.004PMid:15158766 Kong Q, Beel J, Lillehei K. A threshold concept for cancer therapy. Med Hypotheses. 2000;55(1):29-35. https://doi.org/10.1054/mehy.1999.0982PMid:11021322 Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol. 2007;35(4):495-516. https://doi.org/10.1080/01926230701320337PMid:17562483 PMCid:PMC2117903 Basu A. The interplay between apoptosis and cellular senescence: Bcl-2 family proteins as targets for cancer therapy. Pharmacol Ther. 2021:107943. https://doi.org/10.1016/j.pharmthera.2021.107943PMid:34182005 Wang Y-C, Wang L-T, Hung TI, Hong Y-R, Chen C-H, Ho C-J, et al. Severe cellular stress drives apoptosis through a dual control mechanism independently of p53. Cell Death Discov. 2022;8(1):1-5. https://doi.org/10.1038/s41420-022-01078-2PMid:35680784 PMCid:PMC9184497 Li M. The role of P53 up-regulated modulator of apoptosis (PUMA) in ovarian development, cardiovascular and neurodegenerative diseases. Apoptosis. 2021;26(5):235-47. https://doi.org/10.1007/s10495-021-01667-zPMid:33783663 PMCid:PMC8197724 Fu Z-Y, Han X-D, Wang A-H, Liu X-B. Apoptosis of human gastric carcinoma cells induced by Euphorbia esula latex. World J Gastroenterol. 2016;22(13):3564. https://doi.org/10.3748/wjg.v22.i13.3564PMid:27053848 PMCid:PMC4814642 Rezadoost MH, Kumleh HH, Ghasempour A. Cytotoxicity and apoptosis induction in breast cancer, skin cancer and glioblastoma cells by plant extracts. Mol Biol Rep. 2019;46(5):5131-42. https://doi.org/10.1007/s11033-019-04970-wPMid:31317456 Kumar S, Sharma VK, Yadav S, Dey S. Antiproliferative and apoptotic effects of black turtle bean extracts on human breast cancer cell line through extrinsic and intrinsic pathway. Chem Cent J. 2017;11(1):1-10. https://doi.org/10.1186/s13065-017-0281-5PMid:29086840 PMCid:PMC5478552 Patel A, Soni A, Siddiqi NJ, Sharma P. An insight into the anticancer mechanism of Tribulus terrestris extracts on human breast cancer cells. 3 Biotech. 2019;9(2):58. https://doi.org/10.1007/s13205-019-1585-zPMid:30729082 PMCid:PMC6352625 Vacher P, Khadra N, Vacher A-M, Charles E, Bresson-Bepoldin L, Legembre P. Does calcium contribute to the CD95 signaling pathway? Anticancer Drugs. 2011;22(6):481-7. https://doi.org/10.1097/CAD.0b013e32834433eaPMid:21317766 Kaufmann T, Strasser A, Jost PJ. Fas death receptor signalling: roles of Bid and XIAP. Cell Death Differ. 2012;19(1):42-50. https://doi.org/10.1038/cdd.2011.121PMid:21959933 PMCid:PMC3252833 Koncz G, Hueber AO. The Fas/CD95 receptor regulates the death of autoreactive B cells and the selection of antigen-specific B cells. Front Immunol. 2012;3:207. https://doi.org/10.3389/fimmu.2012.00207PMid:22848207 PMCid:PMC3404404 Chen YF, Yang JS, Chang WS, Tsai SC, Peng SF, Zhou YR. Houttuynia cordata Thunb extract modulates G0/G1 arrest and Fas/CD95-mediated death receptor apoptotic cell death in human lung cancer A549 cells. J Biomed Sci. 2013;20(1):18. https://doi.org/10.1186/1423-0127-20-18PMid:23506616 PMCid:PMC3610241 Ostrakhovitch EA, Cherian MG. Inhibition of extracellular signal regulated kinase (ERK) leads to apoptosis inducing factor (AIF) mediated apoptosis in epithelial breast cancer cells: the lack of effect of ERK in p53 mediated copper induced apoptosis. J Cell Biochem. 2005;95(6):1120-34. https://doi.org/10.1002/jcb.20484PMid:15880691
