Vitamin C affects G0/G1 cell cycle and autophagy by downregulating of cyclin D1 in gastric carcinoma cells

Abstract

Vitamin C has re-emerged as a promising anticancer agent. This study attempts to analyze the differential gene expression of profiles GSE11919 to look for some clues, and the most significant cell cycle pathway caused by vitamin C was identified by integrated bioinformatics analysis. Inspired by this, we investigated the effect of vitamin C treatment on gastric carcinoma cells by detection of cell cycle, apoptosis, and autophagy. Vitamin C significantly elevated the percentage of cells at G0/G1 phase, whereas the percentage of S phase cells was decreased. Meanwhile, vitamin C treatment resulted in downregulation of cell cycle-related protein Cyclin D1. We deduced that the downregulation of Cyclin D1 by vitamin C accompanied by significantly increased 5′AMP-activated protein kinase and induced autophagy in MKN45 cells. These results suggest that vitamin C has the antiproliferation effect on gastric carcinoma cells via the regulation of cell cycle and autophagy by Cyclin D1.

Review of the Potential Role of Ascorbate in the Prevention and Treatment of Gynecological Cancers

“…Recent clinical trials found that high-dose IV infusions of ascorbate (1.5-2.2 g/kg, 3× weekly, over 6 weeks) combined with chemotherapeutic agents improved progression-free survival (PFS) or overall survival (OS) in some types of cancer without serious side effects [16,72,76,77]. Under the catalysis of endogenous or exogenous metals such as Fe 3+ , high-dose ascorbate produces large amounts of H 2 O 2 and increases the cellular stress levels, resulting in DNA damage, cell cycle arrest, apoptosis, and autophagy while inhibiting epithelial-mesenchymal transition (EMT) and angiogenesis [5,12,18,71,78]. Therefore, it is currently believed that the antitumor mechanism of ascorbate mainly utilizes its pro-oxidative activity rather than antioxidative activity in most cancer cells [70].…”

Prediction of recurrence of early gastric carcinoma after endoscopic submucosal dissection

“…As one of the clinically common digestive tract malignant tumors, gastric cancer ranks 2 nd among all tumors in terms of mortality rate, seriously affecting the life health and quality of life of patients 1 . Gastric cancer is characterized by insidious onset and rapid progression, and patients often have already been at middle and advanced stages when diagnosed, so early detection, diagnosis and treatment are crucial for improving the treatment outcomes and survival quality 2 .…”