Differential effects of ginkgol C17:1 on cisplatin‑induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells

Li,Yueying; Zhang,Xinchi; Yang,Xiaoming; Liu,Jun; Li,Linjie; Ma,Wenbin; Chen,Min

doi:10.3892/ol.2019.9974

March-2019 Volume 17 Issue 3

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March-2019 Volume 17 Issue 3

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Article Open Access

Differential effects of ginkgol C17:1 on cisplatin‑induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells

Authors:
- Yueying Li
- Xinchi Zhang
- Xiaoming Yang
- Jun Liu
- Linjie Li
- Wenbin Ma
- Min Chen
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Affiliations: Department of Physiology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Food Science and Engineering, School of Food and Biological Engineering, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, Department of Biology, Institute of Life Science, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu 212013, P.R. China

Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 3181-3190
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Published online on: January 25, 2019

https://doi.org/10.3892/ol.2019.9974
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Abstract

Liver cancer is a major healthcare problem and one of the leading causes of cancer‑associated mortality in the world. To date, chemotherapy remains a common method for treating cancer and cisplatin is one of the most widely used chemotherapeutics. However, owing to drug resistance and side effects, it is imperative to identify a novel approach to improve the anticancer effect of cisplatin. Auxiliary chemotherapy drugs with minor toxicity to normal cells may represent a novel strategy for cancer therapy. Previous studies have indicated that ginkgol C17:1 exhibits anticancer effects in liver cancer cells in vitro and in vivo. The antitumor activity of ginkgol C17:1 has been reported in combination with cisplatin in human liver cancer cells. Owing to the route of systemic administration, liver cancer cells and normal hepatocytes were exposed to chemotherapeutics and auxiliary chemotherapy drugs. However, the effects of ginkgol C17:1 in normal hepatocytes remain unclear. In the present study, the biological effects of ginkgol C17:1 alone and as co‑treatment with cisplatin were compared in human hepatoma cells and normal hepatocytes. Consistently, the results confirmed that in human hepatoma HepG2 cells, ginkgol C17:1 or cisplatin alone induced autophagy and apoptosis. The co‑treatment increased cisplatin‑induced apoptosis and inhibited cisplatin‑induced autophagy. In comparison, the treatments in human normal L02 hepatocytes indicated that ginkgol C17:1 alone induced autophagy, whereas cisplatin alone induced apoptosis. The co‑treatment inhibited cisplatin‑induced apoptosis, but enhanced autophagy in L02 cells. Further investigation revealed that the AMP‑activated protein kinase/serine/threonine protein kinase ULK1 and phosphoinositide 3‑kinase/protein kinase B/mammalian target of rapamycin signaling pathways were involved in the underlying regulatory mechanisms. Taken together, the results of the present study provide the first evidence that ginkgol C17:1 protects normal hepatocytes against cisplatin‑induced cytotoxicity while potentiating the anticancer effect of cisplatin chemotherapy. The differential effects on normal and cancer cells suggest that ginkgol C17:1 is a promising candidate for auxiliary chemotherapy.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Differential effects of ginkgol C17:1 on cisplatin‑induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells

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