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

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,...

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Autores principales: Li, Yueying, Zhang, Xinchi, Yang, Xiaoming, Liu, Jun, Li, Linjie, Ma, Wenbin, Chen, Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396107/
https://www.ncbi.nlm.nih.gov/pubmed/30867748
http://dx.doi.org/10.3892/ol.2019.9974
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author Li, Yueying
Zhang, Xinchi
Yang, Xiaoming
Liu, Jun
Li, Linjie
Ma, Wenbin
Chen, Min
author_facet Li, Yueying
Zhang, Xinchi
Yang, Xiaoming
Liu, Jun
Li, Linjie
Ma, Wenbin
Chen, Min
author_sort Li, Yueying
collection PubMed
description 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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spelling pubmed-63961072019-03-13 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 Oncol Lett Articles 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. D.A. Spandidos 2019-03 2019-01-25 /pmc/articles/PMC6396107/ /pubmed/30867748 http://dx.doi.org/10.3892/ol.2019.9974 Text en Copyright: © Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Li, Yueying
Zhang, Xinchi
Yang, Xiaoming
Liu, Jun
Li, Linjie
Ma, Wenbin
Chen, Min
Differential effects of ginkgol C17:1 on cisplatin-induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells
title Differential effects of ginkgol C17:1 on cisplatin-induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells
title_full Differential effects of ginkgol C17:1 on cisplatin-induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells
title_fullStr Differential effects of ginkgol C17:1 on cisplatin-induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells
title_full_unstemmed Differential effects of ginkgol C17:1 on cisplatin-induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells
title_short Differential effects of ginkgol C17:1 on cisplatin-induced cytotoxicity: Protecting human normal L02 hepatocytes versus sensitizing human hepatoma HepG2 cells
title_sort differential effects of ginkgol c17:1 on cisplatin-induced cytotoxicity: protecting human normal l02 hepatocytes versus sensitizing human hepatoma hepg2 cells
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6396107/
https://www.ncbi.nlm.nih.gov/pubmed/30867748
http://dx.doi.org/10.3892/ol.2019.9974
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