Vitamin C Inhibited Pulmonary Metastasis through Activating Nrf2/HO‐1 Pathway

Author:

Man Shuli1ORCID,Bi Jingxian1,Liu Furui1,Xie Wenwen1,Ma Long1

Affiliation:

1. State Key Laboratory of Food Nutrition and Safety Key Laboratory of Industrial Microbiology, Ministry of Education Tianjin Key Laboratory of Industry Microbiology National and Local United Engineering Lab of Metabolic Control Fermentation Technology China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology Tianjin University of Science & Technology Tianjin 300457 China

Abstract

AbstractAs an important nutritional component, vitamin C (Vc) shows good antitumor activity in a variety of cancer, but there are few studies in pulmonary metastasis. In order to verify its anticancer and antimetastatic effect, the study sets up H22 pulmonary metastasis mouse model. The results show that intraperitoneal injection of Vc inhibits pulmonary metastasis through up‐regulating the expression of Nrf2, HO‐1, cleaved caspases 3 and 9, and causing DNA damage and apoptosis which is similar to the pro‐oxidant effect of Vc in p53 null cells (H1299 cells). Meanwhile, oral administration of Vc up‐regulates the expression of p53, directly activates Nrf2/HO‐1 pathway, increases expression of cleaved caspases 3 and 9, and ultimately inhibits pulmonary metastasis, which is the same as the antioxidant result of Vc in p53 wild‐type cells. In addition, Vc inhibits the proliferation and migration of lung cancer cells in a concentration‐dependent manner and has little cytotoxic effects on normal cells. Notably, the experiment further illustrates that besides intravenous Vc, oral Vc significantly inhibits the pulmonary metastasis in mice. All in all, these findings provide new clues for Vc‐treated pulmonary metastasis in clinical research.

Funder

National Natural Science Foundation of China

Publisher

Wiley

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