Anthocyanins and proanthocyanidins synergistically inhibit the growth of gastric cancer cells in vitro: exploring the potential physiological activity of grape and red wine

Abstract

Red wine is rich in anthocyanins and procyanidins which possess multiple health-promoting properties. However, the synergistically anticancer effects of them on gastric cancer cells still undefined. The results showed that combination of malvidin-3-O-(6-O-coumaroyl)-glucoside-5-O-glucoside (M35GC) and procyanidin C1 could effectively inhibited the viability of MKN-28 cells with the lowest IC₅₀ value. Mechanistically, M35GC and procyanidin C1 significantly induced cell apoptosis by reducing the ratio of Bcl-2/Bax, blocked cell cycle in G0/G1 phase by decreasing CDK4 protein and decreased glucose consumption and lactate production during aerobic glycolysis through suppressing the expression of HK2 protein in MKN-28 cells. In conclusion, induction of cell apoptosis and cell cycle arrest, as well as the inhibition of HK2 protein that participates in the glycolytic pathway and the suppression of aerobic glycolysis by M35GC and procyanidin C1 contributed to the anti-cancer effects in gastric cancer.

Keywords:

• Anthocyanins
• procyanidins
• gastric cancer
• aerobic glycolysis
• cell apoptosis
• cell cycle

Authors’ contributions

Yifan Wang: designed and performed the experiments, and wrote the original draft. Xiaolu Tian: wrote the paper and made the modification of the manuscript. Tiantian Cheng: analysed the date and revised the article. Runyu Liu: contributed to experimental design and provided technical assistance. Fuliang Han: provided experimental ideas, financial support, and overall revision of the article. All authors reviewed and revised the manuscript and agreed to the published version of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was financially supported by ‘The National Key R&D Program of China (Grant No. 2016YFD0400500)’ and ‘The National Science and Technology Reform and Development Special Project (106001000000150012)’. We would like to thank the Teaching and Research Core Facility at College of Life Science and Life Science Research Core Services, Northwest A&F University for the technical support.