Grape Seed Proanthocyanidins Induce Autophagy and Modulate Survivin in HepG2 Cells and Inhibit Xenograft Tumor Growth in Vivo.

Lihua Wang,Weidong Huang,Jicheng Zhan

doi:10.3390/nu11122983

Grape Seed Proanthocyanidins Induce Autophagy and Modulate Survivin in HepG2 Cells and Inhibit Xenograft Tumor Growth in Vivo.

Lihua Wang, Weidong Huang + Show 1 more

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https://doi.org/10.3390/nu11122983

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Journal: Nutrients	Publication Date: Dec 6, 2019
Citations: 24	License type: CC BY 4.0

Affiliation: China Agricultural University

Abstract

Liver cancer is one of the leading causes of death worldwide. Although radiotherapy and chemotherapy are effective in general, they present various side effects, significantly limiting the curative effect. Increasing evidence has shown that the dietary intake of phytochemicals plays an essential role in the chemoprevention or chemotherapy of tumors. In this work, HepG2 cells and nude mice with HepG2-derived xenografts were treated with grape seed proanthocyanidins (GSPs). The results showed that GSPs induced autophagy, and inhibition of autophagy increased apoptosis in HepG2 cells. In addition, GSPs also reduced the expression of survivin. Moreover, survivin was involved in GSPs-induced apoptosis. GSPs at 100 mg/kg and 200 mg/kg significantly inhibited the growth of HepG2 cells in nude mice without causing observable toxicity and autophagy, while inducing the phosphorylation of mitogen-activated protein kinase (MAPK) pathway-associated proteins, p-JNK, p-ERK and p-p38 MAPK and reducing the expression of survivin. These results suggested that GSPs might be promising phytochemicals against liver cancer.

Highlights

Liver cancer remains a serious threat to human health
Further confirmation regarding whether grape seed proanthocyanidins (GSPs) could induce autophagy in HepG2 cells was obtained by transfecting these cells with pQCXIP-GFP-LC3 for 24 h followed by treatment with 10 mg/L
To further demonstrate that GSPs treatment could induce autophagy in vitro, HepG2 cells were further stained with acridine orange (AO)

Summary

Introduction

Liver cancer remains a serious threat to human health. Hepatocellular carcinoma (HCC)accounts for about 85–90% of all primary liver malignancies [1]. Liver cancer remains a serious threat to human health. Most liver cancer patients are already in the advanced stage when they are diagnosed, unlike the early stage patients whose malignant tissue can be removed by surgical resection [2]. In vitro and in vivo toxicity experiments have demonstrated that proanthocyanidins are devoid of toxicity [5] and have an anticancer effect on various human cancers, such as colorectal cancer [6,7,8], pancreatic cancer [9], HCC [10,11], non-small cell lung cancer [12,13], squamous cell carcinoma [14], as well as head and neck squamous cancer [15]

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