High-dose vitamin C suppresses the invasion and metastasis of breast cancer cells via inhibiting epithelial-mesenchymal transition

Abstract

Ling-Hui Zeng,1 Qing-Mei Wang,1–3 Lin-Yi Feng,1 Yu-Dun Ke,1 Qian-Zi Xu,1 An-Yi Wei,1 Chong Zhang,1 Rong-Biao Ying2 1Department of Pharmacology, Zhejiang University City College, Hangzhou City, Zhejiang Province 310015, People’s Republic of China; 2Department of Surgical Oncology, Taizhou Cancer Hospital, Wenling City, Zhejiang Province 317500, People’s Republic of China; 3Department of Pharmacy, People’s Hospital of Zhengzhou, Zhengzhou City, Henan Province 450053, People’s Republic of ChinaCorrespondence: Chong ZhangDepartment of Pharmacology, Zhejiang University City College, 50 Huzhou Road, Hangzhou City, Zhejiang Province 310015, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] YingDepartment of Surgical Oncology, Taizhou Cancer Hospital, #50 Zhenxin Road, Wenling City, Zhejiang Province 317500, People’s Republic of ChinaTel/Fax [phone]Email [email protected]: Vitamin C (VC) is a kind of essential nutrient in the body regarded as a canonical antioxidant during the past hundred years. However, the anti-cancer effect of VC is controversial. Our study is trying to clarify the relationship between VC dosage and breast cancer metastasis.Methods: Human breast cancer cell lines Bcap37 and MDA-MB-453 were treated with VC at three different concentrations (low-dose, 0.01 mM; medium-dose, 0.1 mM; high-dose, 2 mM). Wound healing assays were conducted for migration assay; transwell tests were performed to detect the ability of cell invasion. The protein levels were evaluated by Western blot analysis or immunohistochemistry. Tumor xenografts in nude mice were built to test the effects of VC on breast cancer cell proliferation and metastasis.Results: 0.01 and 0.1 mM VC promoted cell migration and invasion when compared with the control group, but 2 mM VC significantly suppressed cell migration and invasion of breast cancer cell lines. High-dose VC increased E-cadherin and reduced Vimentin, indicating that high-dose VC suppressed epithelial-mesenchymal transition (EMT) in breast cancer cells. Besides, high-dose VC inhibited cell invasion promoted by TGF-β1 in breast cancer cells. Meanwhile, high-dose VC reversed the suppression of E-cadherin and enhancement of Vimentin induced by TGF-β1 in breast cancer cells. Furthermore, high-dose VC significantly inhibited breast cancer metastasis in vivo.Conclusion: High-dose VC inhibits cell migration and invasion of breast cancer cell lines through suppressing EMT. Thus, it may be considered as an anticancer drug candidate for breast cancer patients.Keywords: vitamin C, metastasis, TGF-β1, breast cancer

Keywords

• Vitamin C
• metastasis
• TGF-β1
• breast cancer