Baicalein-rich fraction of Oroxylum indicum triggers mitochondrialmediated apoptosis pathway through MAPK transduction in cervical cancer cells
DOI:
https://doi.org/10.11113/mjfas.v17n1.2165Keywords:
Apoptosis, baicalein, cervical cancer, MAPK, Oroxylum indicumAbstract
Baicalein was proved to have an apoptotic effect on a wide range of cancer cells in numerous studies. In this study, the apoptotic effect of baicalein-rich fraction from Oroxylum indicum leaves on human cervical cancer cells (SiHa and HeLa) were investigated. In this case, BRF-induced cell death was regulated by the activation of JNK/p38 and deactivation of ERK. Apart from that, BRF was able to trigger mitochondrial-mediated apoptosis pathway by downregulating Bcl-2 as well as upregulating Bax, caspase-9 and caspase-3. Indeed, MAPK transduction was found to be involved in BRF action in modulating mitochondrial Bcl-2 family, Bcl-2 and Bax. In SiHa cells, ERK and p38 pathway regulated BRF stimulation on mitochondrial-mediated pathway. Yet, BRF-induced this apoptosis pathway in ERK/JNK/p38-dependent manner in HeLa cells. Therefore, BRF induced and augmented the cell death of human cervical cancer cells through MAPK transduction.References
American Cancer Society. 2020. Cancer Facts & Figures 2020.
Dinda, B, Silsarma, I., Dinda, M., & Rudrapaul, P. 2015. Oroxylum indicum (L.) Kurz, an important Asian traditional medicine: From traditional uses to scientific data for its commercial exploitation. J. Ethnopharmacol. 161, 255–278.
Donald, G., Hertzer, K., & Eibl, G. 2012. Baicalein – An intriguing therapeutic phytochemical in pancreatic cancer. Curr. Drug Targets. 13, 1772–1776.
Dong X., Li J. C., Jiang Y. Y., Xia M. Y., Tashiro S. I., Onodera S., & Ikejima T. 2013. p38-NF-ĸB-promoted mitochondria-associated apoptosis and G2/M cell cycle arrest in norcantharidin-treated HeLa cells. J Asian Nat Prod Res. 14, 1008-1019.
Gong, W. Y., Zhao, Z. X., Liu, B. J., Lu, L. W., & Dong, J. C. 2017. Exploring the chemopreventive properties and perspectives of baicalin and its aglycone baicalein in solid tumors. Eur. J. Med. Chem. 126, 844–852.
Grossi V., Peserico A., Tezil T., & Simone C. 2014. p38α MAPK pathway: A key factor in colorectal cancer therapy and chemoresistance. World J. Gastroenterol. 20, 9744-9758.
Huang Q., Wu L. J., Tashiro S. I., Onodera S., Li L. H., & Ikejima T. 2005. Silymarin augments human cervical cancer HeLa cell apoptosis via p38/JNK MAPK pathways in serum-free medium. J Asian Nat Prod Res. 7, 701-709.
Hui K., Yang Y., Shi K., Luo H., Duan J., An J., & Xu C. 2014. The p38 MAPK-regulated PKD1/CREB/Bcl-2 pathway contributes to selenite-induced colorectal cancer cell apoptosis in in vitro and in vivo. Cancer Lett. 354, 189-199.
Jiang L., Song H., Guo H., Wang C., & Lu Z. 2018. Baicalein inhibits proliferation and migration of bladder cancer cell line T24 by down-regulation of microRNA-106. Biomed Pharmacother. 107, 1583-1590.
Kim, E. K., & Choi, E. J. 2010. Pathological roles of MAPK signaling pathways in human diseases. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1802(4), 396–405.
Kim B, Ryu S., & Song B. 2006. JNK- and p38 kinase-mediated phosphorylation of Bax leads to its activation and mitochondrial translocation and to apoptosis of human hepatoma HepG2 cells. J. Biol. Chem. 281, 21256-21265.
Lu Z., & Xu S. 2008. ERK1/2 MAP kinases in cell survival and apoptosis. Life. 58, 621-631.
Mu J., Liu T., Jiang L., Wu X., Cao Y., Li M., Dong Q., Liu Y., & Hu H. 2016. The traditional Chinese medicine baicalein potently inhibits gastric cancer cells. J. Cancer. 7, 453-462.
Muhamad, N. A., Kamaluddin, M. A., Adon, M. Y., Noh, M. A., Bakhtiar, M. F., Ibrahim Tamim, N. S., Aris, T. 2015. Survival rates of cervical cancer patients in Malaysia. Asian Pac Jl of Cancer P, 16(7), 3067–3072.
Papa S., Choy P. M., & Bubici C. 2018. The ERK and JNK pathways in the regulation of metabolic reprogramming. Oncogene.
Roskoski, R. 2012. ERK1/2 MAP kinases: Structure, function, and regulation. Pharmacological Research, 66(2), 105–143.
Stramucci L., Pranteda A., & Bossi G. 2018. Insights of crosstalk between p53 protein and the MKK3/MKK6/p38 MAPK signaling pathway in cancer. Cancers. 10, 9-19.
Sun Y., Liu W. Z., Liu T., Feng X., Yang N., & Zhou H. F. 2015. Signaling pathway of MAPK/ERK in cell proliferation, differentiation, migration, senesence and apoptosis. J. Recept. Sig. Transd. 35, 600-604.
Takahashi, H., Chen, M. C., Pham, H., Angst, E., King, J. C., Park, J., & Eibl, G. 2011. Baicalein, a component of Scutellaria baicalensis, induces apoptosis by Mcl-1 down-regulation in human pancreatic cancer cells. Molecular Cell Research. 1813, 1465–1474.
Wahab N. H. & Che Mat N. F. 2018. Baicalein-rich fraction of Oroxylum indicum leaves induces apoptosis by repressing E6 and E7 expression in HPV-associated cervical cancer cell lines. Int. J. Res. Pharm. Sci. 9, 108-117.
Wang C. Z., Zhang C. F., Chen L., Anderson S., Lu F., & Yuan C. S. 2015. Colon cancer chemopreventive effects of baicalein, an active enteric microbiome metabolite from baicalin. Int. J. Oncol. 47, 1749-1758.
Wu, X., Yang, Z., Dang, H., Peng, H., & Dai, Z. 2017. Baicalein inhibits the proliferation of cervical cancer cells through the GSK3ß-dependent pathway. Oncology Research, 26, 645–653.
Yating Q., Yuan Y., Wei Z., Qing G., Xingwei W., Qiu Q., & Lili Y. 2014. Oxidized LDL induces apoptosis of human retinal pigment epithelium through activation of ERK-Bax/Bcl-2 signaling pathways. Curr. Eye Res. 40, 415-422.
Ye H., Zhang Y., Wang Y., Xia J., Mao X., & Yu X. 2017. The restraining effect of baicalein and U0126 on human cervical cancer cell line HeLa. Mol. Med. Rep. 16, 957-63.
Yong P., Qingwang L., Kun L., Hongwei Z., Zengsheng H., Fenglin L., Sun M., & Yanxia Z. 2011. Antitumor activity of baicalein on the mice bearing U14 cervical cancer. J. Biotechnol. 10, 14169-14176.
Zazali K. E., Abdullah H., & Jamil N. I. N. 2013. Methanol extract of Oroxylum indicum leaves induces G1/S cell cycle arrest in HeLa cells via p53-mediated pathway. International Journal of Medicinal Plant Research. 2, 225-237.
Zhou R. T., He M., Yu Z., Liang Y., Nie Y., Tai S., & Teng C. B. 2017. Baicalein inhibits pancreatic cancer cell proliferation and invasion via suppression of NEDD9 expression and its downstream Akt and ERK signaling pathways. Oncotarget. 8, 56351-56363.
