Hederagenin Induces Apoptosis of Human Hepatoma HepG2 Cells via the Mitochondrial Pathway
- Authors: Liu Z.1, Tan X.1, Peng L.2, Gao W.3, Zeng P.4
-
Affiliations:
- Affiliated Hospital,, Hunan Academy of Traditional Chinese Medicine
- College of Traditional Chinese Medicine,, Hunan University of Chinese Medicine
- College of Traditional Chinese Medicine, Hunan University of Chinese Medicine,
- Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine
- Issue: Vol 27, No 10 (2024)
- Pages: 1495-1503
- Section: Chemistry
- URL: https://rjeid.com/1386-2073/article/view/643817
- DOI: https://doi.org/10.2174/0113862073254353230925074944
- ID: 643817
Cite item
Full Text
Abstract
Objective::The objective of this study is to assess the antitumor effects of hederagenin (HDG) in liver cancer (LC) cells and explore the related mechanisms.
Methods and Materials::HepG2 cells were treated with HDG and cisplatin, respectively. The CCK8 assay was used to detect cell activity, DAPI staining was used to detect the proportion of living cells, TUNEL assay to detect the proportion of apoptotic cells, flow cytometry to detect the membrane potential, fluoroscopic electron microscopy to detect microstructural changes to the mitochondrial, and western blot analysis and high-content screening to detect apoptosisrelated proteins.
Results::Treatment with HDG inhibited the growth of HepG2 cells, decreased the proportion of viable cells, increased the proportion of apoptotic cells, and significantly increased the proportion of cells in the G1 phase. Fluorescence staining showed that HDG damaged the mitochondria of HepG2 cells and significantly decreased the number of mitochondria. Flow cytometry showed that HDG decreased the mitochondrial membrane potential of HepG2 cells. Observations by electron microscopy showed that HDG caused swelling and vacuole formation of the mitochondria of HepG2 cells. HDG significantly reduced the average fluorescence intensity of Bcl-2 in HepG2 cells and significantly increased that of the pro-apoptosis proteins Bax, Cytochrome-c, and Caspase-3.
Conclusion::HDG induced apoptosis of HepG2 cells via the mitochondrial pathway.
Keywords
About the authors
Zhuo Liu
Affiliated Hospital,, Hunan Academy of Traditional Chinese Medicine
Email: info@benthamscience.net
Xiaoning Tan
Affiliated Hospital,, Hunan Academy of Traditional Chinese Medicine
Email: info@benthamscience.net
Lian Peng
College of Traditional Chinese Medicine,, Hunan University of Chinese Medicine
Email: info@benthamscience.net
Wenhui Gao
College of Traditional Chinese Medicine, Hunan University of Chinese Medicine,
Email: info@benthamscience.net
Puhua Zeng
Affiliated Hospital, Hunan Academy of Traditional Chinese Medicine
Author for correspondence.
Email: info@benthamscience.net
References
- Pinyol, R.; Torrecilla, S.; Wang, H.; Montironi, C.; Piqué-Gili, M.; Torres-Martin, M.; Wei-Qiang, L.; Willoughby, C.E.; Ramadori, P.; Andreu-Oller, C.; Taik, P.; Lee, Y.A.; Moeini, A.; Peix, J.; Faure-Dupuy, S.; Riedl, T.; Schuehle, S.; Oliveira, C.P.; Alves, V.A.; Boffetta, P.; Lachenmayer, A.; Roessler, S.; Minguez, B.; Schirmacher, P.; Dufour, J.F.; Thung, S.N.; Reeves, H.L.; Carrilho, F.J.; Chang, C.; Uzilov, A.V.; Heikenwalder, M.; Sanyal, A.; Friedman, S.L.; Sia, D.; Llovet, J.M. Molecular characterisation of hepatocellular carcinoma in patients with non-alcoholic steatohepatitis. J. Hepatol., 2021, 75(4), 865-878. doi: 10.1016/j.jhep.2021.04.049 PMID: 33992698
- Ali, H.; Dixit, S.; Ali, D.; Ali, B.A.; Alkahtane, A.A.; Alarifi, S.; Alakahtani, S. Isolation and evaluation of biological efficacy of quercetol in human hepatic carcinoma cells. Drug Des. Devel. Ther., 2016, 10, 155-162. doi: 10.2147/DDDT.S95275 PMID: 26792982
- Wang, X.; Fang, G.; Pang, Y. Chinese medicines in the treatment of prostate cancer: From formulas to extracts and compounds. Nutrients, 2018, 10(3), 283. doi: 10.3390/nu10030283 PMID: 29495626
- Zeng, J.; Huang, T.; Xue, M.; Chen, J.; Feng, L.; Du, R.; Feng, Y. Current knowledge and development of hederagenin as a promising medicinal agent: A comprehensive review. RSC Adv., 2018, 8(43), 24188-24202. doi: 10.1039/C8RA03666G PMID: 35539158
- Wang, K.; Liu, X.; Liu, Q.; Ho, I.; Wei, X.; Yin, T.; Zhan, Y.; Zhang, W.; Zhang, W.; Chen, B.; Gu, J.; Tan, Y.; Zhang, L.; Chan, M.T.; Wu, W.K.; Du, B.; Xiao, J. Hederagenin potentiated cisplatin- and paclitaxel-mediated cytotoxicity by impairing autophagy in lung cancer cells. Cell Death Dis., 2020, 11(8), 611. doi: 10.1038/s41419-020-02880-5 PMID: 32792495
- Kim, E.H.; Baek, S.; Shin, D.; Lee, J.; Roh, J.L. Hederagenin induces apoptosis in cisplatin-resistant head and neck cancer cells by inhibiting the Nrf2-ARE antioxidant pathway. Oxid. Med. Cell. Longev., 2017, 2017, 1-12. doi: 10.1155/2017/5498908 PMID: 29456786
- Wang, F.; Bai, J.; Li, F.; Liu, J.; Wang, Y.; Li, N.; Wang, Y.; Xu, J.; Liu, W.; Xu, L.; Chen, L. Investigation of the mechanism of the anti-cancer effects of Astragalus propinquus Schischkin and Pinellia pedatisecta Schott (A&P) on melanoma via network pharmacology and experimental verification. Front. Pharmacol., 2022, 13, 895738. doi: 10.3389/fphar.2022.895738 PMID: 36034875
- Iorio, R.; Celenza, G.; Petricca, S. Mitophagy: Molecular mechanisms, new concepts on parkin activation and the emerging role of AMPK/ULK1 Axis. Cells, 2021, 11(1), 30. doi: 10.3390/cells11010030 PMID: 35011593
- Zhao, R.Z.; Jiang, S.; Zhang, L.; Yu, Z.B. Mitochondrial electron transport chain, ROS generation and uncoupling (Review). Int. J. Mol. Med., 2019, 44(1), 3-15. doi: 10.3892/ijmm.2019.4188 PMID: 31115493
- Bencze, G.; Bencze, S.; Rivera, K.D.; Watson, J.D.; Hidvegi, M.; Orfi, L.; Tonks, N.K.; Pappin, D.J. Mito-oncology agent: fermented extract suppresses the Warburg effect, restores oxidative mitochondrial activity, and inhibits in vivo tumor growth. Sci. Rep., 2020, 10(1), 14174. doi: 10.1038/s41598-020-71118-3 PMID: 32843660
- Song, L.; Li, Q.; Shi, H.; Yue, H. Deciphering the molecular mechanism of red raspberry in apoptosis of liver cancer cells. Evid. Based Complement. Alternat. Med., 2022, 2022, 1-7. doi: 10.1155/2022/2026865 PMID: 35529935
- Cheng, D.; Gao, L.; Su, S.; Sargsyan, D.; Wu, R.; Raskin, I.; Kong, A.N. Moringa isothiocyanate activates Nrf2: Potential role in diabetic nephropathy. AAPS J., 2019, 21(2), 31. doi: 10.1208/s12248-019-0301-6 PMID: 30783799
- Sun, Y.; Liu, Y.; Ma, X.; Hu, H. The influence of cell cycle regulation on chemotherapy. Int. J. Mol. Sci., 2021, 22(13), 6923. doi: 10.3390/ijms22136923 PMID: 34203270
- Kong, C.; Xu, B.; Qiu, G.; Wei, M.; Zhang, M.; Bao, S.; Tang, J.; Li, L.; Liu, J. Multifunctional nanoparticles-mediated ptt/pdt synergistic immune activation and antitumor activity combined with anti-PD-L1 immunotherapy for breast cancer treatment. Int. J. Nanomed., 2022, 17, 5391-5411. doi: 10.2147/IJN.S373282 PMID: 36419717
- Pérez-Herrero, E.; Fernández-Medarde, A. Advanced targeted therapies in cancer: Drug nanocarriers, the future of chemotherapy. Eur. J. Pharm. Biopharm., 2015, 93, 52-79. doi: 10.1016/j.ejpb.2015.03.018 PMID: 25813885
- Lee, J.; Gong, Y.X.; Xie, D.P.; Jeong, H.; Seo, H.; Kim, J.; Park, Y.H.; Sun, H.N.; Kwon, T. Anticancer effect of ERM210 on liver cancer cells through ROS/Mitochondria-dependent apoptosis signaling pathways. In Vivo, 2021, 35(5), 2599-2608. doi: 10.21873/invivo.12542 PMID: 34410947
- Zhang, L.; Li, S.; Wang, R.; Chen, C.; Ma, W.; Cai, H. Cytokine augments the sorafenib-induced apoptosis in Huh7 liver cancer cell by inducing mitochondrial fragmentation and activating MAPK-JNK signalling pathway. Biomed. Pharmacother., 2019, 110, 213-223.
- Lulli, M.; Del Coco, L.; Mello, T.; Sukowati, C.; Madiai, S.; Gragnani, L.; Forte, P.; Fanizzi, F.P.; Mazzocca, A.; Rombouts, K.; Galli, A.; Carloni, V. DNA damage response protein CHK2 regulates metabolism in liver cancer. Cancer Res., 2021, 81(11), 2861-2873. doi: 10.1158/0008-5472.CAN-20-3134 PMID: 33762357
- Barrios-Maya, M.A.; Ruiz-Ramírez, A.; Quezada, H.; Céspedes Acuña, C.L.; El-Hafidi, M. Palmitoyl-CoA effect on cytochrome c release, a key process of apoptosis, from liver mitochondria of rat with sucrose diet-induced obesity. Food Chem. Toxicol., 2021, 154, 112351. doi: 10.1016/j.fct.2021.112351 PMID: 34171418
- Li, J.; Cui, J.; Li, Z.; Fu, X.; Li, J.; Li, H.; Wang, S.; Zhang, M. ORP8 induces apoptosis by releasing cytochromec from mitochondria in non small cell lung cancer. Oncol. Rep., 2020, 43(5), 1516-1524. doi: 10.3892/or.2020.7517 PMID: 32323800
Supplementary files
