Tubuloside A Induces DNA Damage and Apoptosis in Human Ovarian Cancer A2780 Cells


Abstract views: 75 / PDF downloads: 62

Authors

DOI:

https://doi.org/10.58600/eurjther1951

Keywords:

Tubuloside A, cell viability, genotoxicity, apoptosis, ovarian cancer

Abstract

Objective: Ovarian carcinoma is one of the most lethal gynecological cancers, as it responds later to diagnostic methods and therapeutic responses in advanced stages. Many phytochemical compounds have been shown to be protective against cancer. Tubuloside A (TbA) is the main compound extracted from the plant Cistanche tubulosa, and its pharmacological effects have been studied broadly. Until now, the role of TbA in human ovarian carcinoma is unknown. The goal of this study was to evaluate the effects of TbA on DNA damage and apoptosis in A2780 cell lines.

Methods: Different concentrations of TbA (1, 5, 25, 50, and 100 µM) and 5- Fluorouracil (1, 5, 25, 50, and 100 µM) treated to the human ovarian cancer cell (A2780) line for 24 h. After incubation, cell viability (MTT), genotoxicity (Comet analyses), and mRNA expression analyses of apoptotic markers (Caspase-3, Bax, Bcl-2, and p53) were determined.

Results: Applied doses of 50 and 100 µM of TbA and 5- Fluorouracil significantly reduced cell viability. Also, TbA increased DNA damage in A2780 cells. Additionally, TbA up-regulated the mRNA expressions of caspase-3, Bax, and p53, which are apoptosis-inducing factors, and down-regulated the expression of Bcl-2.

Conclusion: These results show that the p53 and caspase-3 signaling pathways may exhibit a key role in TbA-associated effects on A2780 cells and TbA may be a potential drug aspirant for ovarian cancer therapy.

Metrics

Metrics Loading ...

References

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68: 394–424. https://doi.org/10.3322/caac.21492

Luo J, Zhou J, Cheng Q, Zhou C, Ding Z (2014) Role of microRNA-133a in epithelial ovarian cancer pathogenesis and progression. Oncol Lett 7: 1043-1048. PubMed/NCBI. https://doi.org/10.3892/ol.2014.1841

Goff BA (2022). Ovarian cancer is not so silent. Obstet Gynecol 139: 155-156. https://doi.org/10.1097/AOG.0000000000004664

. Yang X, Zheng F, Xing H, Gao Q, Wei W, Lu Y, Wang S, Zhou J, Hu W, Ma D (2004) Resistance to chemotherapy-induced apoptosis via decreased caspase-3 activity and overexpression of antiapoptotic proteins in ovarian cancer. J Cancer Res Clin Oncol 130: 423-428. https://doi.org/10.1007/s00432-004-0556-9

Yu G, Li N, Zhao Y, Wang W, Feng XL (2018) Salidroside induces apoptosis in human ovarian cancer SKOV3 and A2780 cells through the p53 signaling pathway. Oncol Lett 15: 6513-6518. https://doi.org/10.3892/ol.2018.8090

Adams JM, Cory S (2007) The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene 26: 1324-1337. https://doi.org/10.1038/sj.onc.1210220

Vogler M (2012) BCL2A1: The underdog in the BCL2 family. Cell Death Differ 19: 67-74. https://doi.org/10.1038/cdd.2011.158

Azmi AS, Wang Z, Philip PA, Mohammad RM, Sarkar FH (2011) Emerging Bcl-2 inhibitors for the treatment of cancer. Expert Opin Emerg Drugs 16: 59-70. https://doi.org/10.1517/14728214.2010.515210

Borner C (2003) The Bcl-2 protein family: Sensors and checkpoints for life-or-death decisions. Mol Immunol 39: 615-647. https://doi.org/10.1016/S0161-5890(02)00252-3

Pfeffer CM, Singh AT (2018) Apoptosis: A target for anticancer therapy. Int J Mol Sci 19: 448. https://doi.org/10.3390/ijms19020448

Al-Snafi AE (2020) Bioactive metabolites and pharmacology of Cistanche tubulosa-A review. IOSR J Pharm 10: 37-46.

Morikawa T, Xie H, Pan Y, Ninomiya K, Yuan D, Jia X, Yoshikawa M, Nakamura S, Matsuda H, Muraoka O. A (2019) A review of biologically active natural products from a desert plant Cistanche tubulosa. Chem Pharm Bull (Tokyo) 67: 675-689. https://doi.org/10.1248/cpb.c19-00008

Xiong WT, Gu L, Wang C, Sun HX, Liu X (2013) Anti-hyperglycemic and hypolipidemic effects of Cistanche tubulosa in type 2 diabetic db/db mice. J Ethnopharmacol 150: 935-945. https://doi.org/10.1016/j.jep.2013.09.027

Zhu K, Meng Z, Tian Y, Gu R, Xu Z, Fang H, Liu W, Huang W, Ding G, Xiao W (2021). Hypoglycemic and hypolipidemic effects of total glycosides of Cistanche tubulosa in diet/streptozotocin-induced diabetic rats. J Ethnopharmacol 76: 113991. https://doi.org/10.1016/j.jep.2021.113991

Deng M, Zhao JY, Ju XD, Tu PF, Jiang Y, Li ZB (2004) Protective effect of tubuloside B on TNFalpha-induced apoptosis in neuronal cells. Acta Pharmacol Sin 25: 1276-1284.

Ayupbek A, Ziyavitdinov JF, Ishimov UJ, Sagdiev NZ, Kuznetsova NN, Ke-lin H, Aisa HA (2012) Phenylethanoid glycosides from Cistanche tubulosa. Chem Nat Compd 47: 985-987. https://doi.org/10.1007/s10600-012-0123-6

Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods 65: 55-63. https://doi.org/10.1016/0022-1759(83)90303-4

Singh NP, Mccoy MT, Tice RR, Schneider EL (1988) A simple technique for quantitation of low levels of DNA damage in individual cells. Exp Cell Res 175: 184-191. https://doi.org/10.1016/0014-4827(88)90265-0

Kumaravel TS, Vilhar B, Faux SP, Jha AN (2009) Comet Assay measurements: A perspective. Cell Biol Toxicol 25: 53-64. https://doi.org/10.1007/s10565-007-9043-9

Kalendar R, Lee D, Schulman AH (2014) FastPCR software for PCR, in silico PCR, and oligonucleotide assembly and analysis. Methods Mol Biol. 1116:271-302. https://doi.org/10.1007/978-1-62703-764-8_18

Pfaffl MW (2021). A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Asids Research Vol. 29, No. 9. https://doi.org/10.1093/nar/29.9.e45

Al-Snafi AE (2020) Bioactive metabolites and pharmacology of Cistanche tubulosa-A review. IOSR J Pharm 10: 37-46.

Wu CR, Lin HC, Su MH (2014) Reversal by aqueous extracts of Cistanche tubulosa from behavioral deficits in Alzheimer’s disease-like rat model: Relevance for amyloid deposition and central neurotransmitter function. BMC Complement Altern Med 14: 202. https://doi.org/10.1186/1472-6882-14-202

Sheng G, Pu X, Lei L, Tu P, Li C (2002) Tubuloside B from Cistanche salsa rescues the PC12 neuronal cells from 1-methyl-4-phenylpyridinium ion-induced apoptosis and oxidative stress. Planta Med 68: 966-970. https://doi.org/10.1055/s-2002-35667

Inoue M, Ueda M, Ogihara Y, Saracoglu I (1998) Induction of apoptotic cell death in HL-60 cells by acteoside, a phenylpropanoid glycoside. Biol Pharm Bull 21: 81-83. https://doi.org/10.1248/bpb.21.81

Zhou L, Feng Y, Jin Y, Liu X, Sui H, Chai N, Chen X, Liu N, Ji Q, Wang Y, Li Q (2014) Verbascoside promotes apoptosis by regulating HIPK2-p53 signaling in human colorectal cancer. BMC Cancer 14: 747. https://doi.org/10.1186/1471-2407-14-747

Dong L, Wang H, Niu J, Zou M, Wu N, Yu D, Wang Y, Zou Z (2015a) Echinacoside induces apoptotic cancer cell death by inhibiting the nucleotide pool sanitizing enzyme MTH1. OncoTargets Ther 8: 3649-3664.

Dong L, Yu D, Wu N, Wang H, Niu J, Wang Y, Zou Z (2015b). Echinacoside induces apoptosis in human SW480 colorectal cancer cells by induction of oxidative DNA damages. Int J Mol Sci 16: 14655-14668. https://doi.org/10.3390/ijms160714655

Jeon E, Chung KS, An HJ (2016) Anti-proliferation effects of Cistanches salsa on the progression of benign prostatic hyperplasia. Can J Physiol Pharmacol 94: 104-111. https://doi.org/10.1139/cjpp-2015-0112

Qi X, Hou X, Su D, He Z, Zhao J, Liu T (2022) Effect of PhenylEthanol Glycosides from Cistanche Tubulosa on Autophagy and Apoptosis in H22 Tumor-Bearing Mice. Evid Based Complement Alternat Med 2022: 2022. https://doi.org/10.1155/2022/3993445

Yuan P, Fu C, Yang Y, Adila A, Zhou F, Wei X, Wang W, Lv J, Li Y, Xia L, Li J (2021) Cistanche tubulosa phenylethanoid glycosides induce apoptosis of hepatocellular carcinoma cells by mitochondria-dependent and MAPK pathways and enhance antitumor effect through combination with cisplatin. Integr Cancer Ther 20: 15347354211013085. https://doi.org/10.1177/15347354211013085

Fu C, Li J, Aipire A, Xia L, Yang Y, Chen Q, Lv J, Wang X, Li J (2019) Cistanche tubulosa phenylethanoid glycosides induce apoptosis in Eca 109 cells via the mitochondria dependent pathway. Oncol Lett 17: 303-313.

Xia B, Wang J (2019) Effects of adenosine on apoptosis of ovarian cancer A2780 cells via ROS and caspase pathways. Onco Targets Ther 12: 9473-9480. https://doi.org/10.2147/OTT.S216620

Figure 4

Downloads

Published

2023-12-26

How to Cite

Türeyen, A., Zemheri Navruz, F., Günay, S., Erden, Y., & Ince, S. (2023). Tubuloside A Induces DNA Damage and Apoptosis in Human Ovarian Cancer A2780 Cells. European Journal of Therapeutics, 29(4), 900–906. https://doi.org/10.58600/eurjther1951

Issue

Section

Original Articles

Categories