High-Dose Vitamin C Tends to Kill Colorectal Cancer with High MALAT1 Expression

Abstract

Background. Vitamin C (Vc) deficiency is frequently observed in cancer sites and has been proposed to have an antitumor effect. However, the mechanism of Vc’s killing effect is not clear. Besides, epigenetic alterations exhibit significant effects on colorectal cancer (CRC). This study aimed to explore the mechanism of Vc’s killing effect and its association to epigenetic alterations in CRC. Methods. Cell morphology, apoptosis, proliferation, and cycle were assayed to test Vc’s suppressive function in CRC cell lines. Xenograft and peritoneal implantation metastasis models were performed to evaluate the high-dose Vc’s inhibitory effect on tumor growth and metastasis. Immunohistochemistry was used to measure CD31 expression in solid tumors. A literature summary was applied for screening differently expressed long noncoding RNAs (lncRNAs) in CRC tissues and was closely associated with CRC progression. The qPCR was used to detect the expression of these lncRNAs. The association between Vc and metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was evaluated in MALAT1-transfected CRC cells and a xenograft model. Results. Vc was confirmed to function in proliferation suppression, apoptosis induction, and S phase arresting in CRC cell lines. High-dose Vc, but not physiologically low-dose Vc, was identified as a suppressive function on tumor growth in xenograft models and an inhibitory effect on implantation metastasis in peritoneal implantation metastasis mice. Furthermore, a consistent downregulation of MALAT1 induced by Vc was verified among CRC cell lines and tumor tissues from both mouse models. Finally, experiments on MALAT1-knockdown CRC cells and its xenograft model suggested that Vc had a tendency in killing CRC with high MALAT1 expression. Conclusions. Our findings demonstrate that high-dose Vc has more efficiency in suppressing CRC with higher MALAT1 expression. It gives high-dose Vc the possibility of a better curative effect on CRC with overexpressed MALAT1. Further clinical studies are still needed.

Composite dietary antioxidant index and the risk of colorectal cancer: Findings from the Singapore Chinese Health Study

“…Prior studies for the effect of individual antioxidants on the development of CRC have been conducted, including vitamin A, vitamin C, vitamin E, selenium, manganese and zinc. Vitamins C and E are recommended to be protective agents against cancer 10‐13 . Minerals such as selenium, manganese and zinc are also considered to be essential elements in CRC prevention, 11,18,19 whereas several studies did not find a significant protective effect of vitamin A against the development of CRC 15‐17 .…”

“…Vitamins C and E are recommended to be protective agents against cancer. [10][11][12][13] Minerals such as selenium, manganese and zinc are also considered to be essential elements in CRC prevention, 11,18,19 whereas several studies did not find a significant protective effect of vitamin A against the development of CRC. [15][16][17] A prospective cohort study reported an inverse relationship between high selenium intake and CRC risk.…”

“…Epidemiological studies on individual dietary antioxidants such as vitamins and minerals and the risk of CRC have been conducted previously and produced inconsistent results 10‐31 . Randomized clinical trials evaluating the antioxidant supplementation did not yield consistent data in support of the protective effect against the development of CRC.…”

Dietary Factors Modulating Colorectal Carcinogenesis

“…The same proves true for other dietary components, such as polyphenols [ 113 ] vitamins [ 114 , 115 , 116 ], and minerals [ 116 , 117 ] alone or in combination.…”

MALAT1-related signaling pathways in colorectal cancer

“…It has been found that high-dose Vitamin C administration has an inhibitory effect on MALAT1 and CRC metastasis [ 79 ].…”