Effects of ginkgol C17:1 on cisplatin‑induced autophagy and apoptosis in HepG2 cells

Liu, Jun; Li, Yueying; Xiaoming, Yang; Yan, Dong; Wu, Jing; Chen, Min

doi:10.3892/ol.2017.7398

Cited by 8 publications

(10 citation statements)

References 55 publications

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“…HepG2 cells were cultured in DMEM and L02 cells were cultured in RPMI-1640 medium supplemented with 10% FBS at 37°C in a humidified atmosphere containing 5% CO 2 . Where indicated, cells were treated for 24 h with serial dilution concentrations of ginkgol C17:1 (0, 10, 20, 40, 80, or 160 µg/ml) and/or cisplatin (0, 1, 2, 4, 8 or 16 µg/ml), on the basis of previously established concentrations (24,27).…”

Section: Methodsmentioning

confidence: 99%

“…Protein extraction was performed according to a standard procedure outlined in previous studies (24,27). Lysis buffer (pH 7.4) for protein extraction was composed of 50 mM Tris, 150 mM NaCl, 1 mM ethyl- enediaminetetraacetic acid and 1% Triton X-100.…”

Section: Methodsmentioning

confidence: 99%

“…The cell nuclei in different treatment groups were visualized under a fluorescence microscope at a magnification of ×20. The numbers of nucleus aberrations from five different wells with the same treatment were determined (24) using Image J. The results are from ≥3 individual experiments.…”

Section: Methodsmentioning

confidence: 99%

“…Consistent with the study by Chen et al (22), our previous study revealed that EGb could effectively inhibit cell division and induce apoptosis in cancer cell line SMMC-7721 (23). Recently, ginkgol C17:1 was demonstrated to promote cisplatin-induced apoptosis and suppress cisplatin-induced autophagy in liver cancer HepG2 cells (24). Since oral administration is the common route for chemotherapeutical agents and auxiliary chemotherapy drugs, normal cells are inevitably also exposed to chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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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

Zhang

Xiaoming

et al. 2019

Oncol Lett

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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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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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

Zhang

Xiaoming

et al. 2019

Oncol Lett

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“…The method was on the basis of Liu's experiment (J. Liu et al., ). HepG2 cells were plated into 24‐well plates (5 × 10 4 cells/well) for culture.…”

Section: Methodsmentioning

confidence: 99%

Effect of Alkylresorcinols on Autophagy, Migration, and Invasion of HepG2 Cells

Guo

Xiaoming

2019

Journal of Food Science

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Alkylresorcinols are phenolic lipids that mainly exist in the cortex of grains, and they exhibit anticancer activity against various cancer cells in vitro. However, the underlying action mechanisms are still unclear. In our study, the influence of alkylresorcinols C19:0 and C21:0 (ARs) upon migration, invasion, and autophagy in human hepatoblastoma HepG2 cells was evaluated. Results showed that ARs at 80 and 160 µg/mL significantly suppressed cells proliferation, migration, and invasion, downregulated the expression of proteins RhoA and MMP‐7 associated with migration and invasion. ARs at 160 µg/mL, the rate of LC3 puncta was appreciably increased. After autophagy was blocked by 3‐MA or CQ, the expression of LC3II was significantly increased in 3‐MA+ARs group and p62 was significantly decreased in CQ+ARs group. The results indicate that ARs may promote autophagic flow. ARs (80, 160 µg/mL) significantly inhibited the expression of proteins p‐mTOR, p‐PI3K, and p‐Akt related to the PI3K/Akt pathway. The results of the present study suggest that ARs can activate autophagy and suppresses the biological behaviors of HepG2 cells by inhibiting the activation of MMP‐7, Rho/Rho‐associated protein kinase, and activation of the phosphatidylinositol 3‐kinase/Akt signaling pathway. Practical Application The anticancer mechanism of ARs in wheat bran was studied, which provided a basis for the development of anticancer functional auxiliary food with wheat bran as raw material. It is of great practical significance to promote the effective utilization of grain processing by‐products and improve the economic benefits of the grain industry.

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Ginkgolic Acids Impair Mitochondrial Function by Decreasing Mitochondrial Biogenesis and Promoting FUNDC1-Dependent Mitophagy

Wang¹,

Wang²,

Ruan³

et al. 2019

J. Agric. Food Chem.

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Ginkgolic acids (GAs) are found in the leaves, nuts, and testa of Ginkgo biloba and have been reported to exhibit antitumor, antibacterial, and pro-apoptotic activities. However, their role in mitochondrial function is still unclear. Our previous study showed that genes related to the mitochondria present significant changes in GA-treated mouse bone marrow stromal cells. We hypothesize that GAs may regulate mitochondrial function. Here, we found that GA treatment induced mitochondrial fragmentation, reduced mtDNA copy numbers and mitochondrial protein levels, and impaired mitochondrial adenosine 5′-triphosphate production and oxygen consumption. The GA-induced mitochondrial mass loss may be due to decreased mitochondrial biogenesis. In addition, abolishing autophagy by Atg7 knockout or the administration of an autophagy inhibitor can restore the GA-induced decrease in mitochondrial mass. Furthermore, FUNDC1 knockdown restored the GA-induced changes in mitochondrial mass reduction and mitochondrial membrane potential loss. Together, our studies demonstrated that GAs impaired mitochondrial function by decreasing mitochondrial biogenesis and promoting FUNDC1dependent mitophagy.

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Effects of ginkgol C17:1 on cisplatin‑induced autophagy and apoptosis in HepG2 cells

Cited by 8 publications

References 55 publications

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

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

Effect of Alkylresorcinols on Autophagy, Migration, and Invasion of HepG2 Cells

Ginkgolic Acids Impair Mitochondrial Function by Decreasing Mitochondrial Biogenesis and Promoting FUNDC1-Dependent Mitophagy

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