Enhanced Anticancer Effect of Adding Magnesium to Vitamin C Therapy: Inhibition of Hormetic Response by SVCT-2 Activation

Sungrae Cho; Jin Sung Chae; Hocheol Shin; Yujeong Shin; Youngwook Kim; Eui-Joon Kil; Hee-Seong Byun; Sang-Ho Cho; Seyeon Park; Sukchan Lee; Chang-Hwan Yeom

doi:10.1016/j.tranon.2019.10.017

Enhanced Anticancer Effect of Adding Magnesium to Vitamin C Therapy: Inhibition of Hormetic Response by SVCT-2 Activation

Transl Oncol. 2020 Feb;13(2):401-409. doi: 10.1016/j.tranon.2019.10.017. Epub 2019 Dec 31.

Authors

Affiliations

¹ College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea.
² Yeom Chang-Hwan Hospital, Seoul, 06605, Republic of Korea.
³ Department of Applied Chemistry, Dongduk Women's University, Seoul, 02748, Republic of Korea.
⁴ Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul, 06351, Republic of Korea.
⁵ College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea. Electronic address: cell4u@skku.edu.
⁶ Yeom Chang-Hwan Hospital, Seoul, 06605, Republic of Korea. Electronic address: lymphych@hanmail.net.

Abstract

l-Ascorbic acid (vitamin C, AA) is known as an antioxidant, but at high concentrations, AA can kill cancer cells through a prooxidant property. Sodium-dependent vitamin C transporter family-2 (SVCT-2) determines the cellular uptake of AA, and the activity of SVCT-2 is directly related to the anticancer activity of AA. Cancer cells that showed high SVCT-2 expression levels were more sensitive to AA treatment than cancer cells with low SVCT-2 expression levels. Cells with low SVCT-2 expression showed a hormetic response to a low dose of AA. Magnesium ions, which are known to activate SVCT-2, could increase the V_max value of SVCT-2, so we investigated whether providing magnesium supplements to cancer cells with low SVCT-2 expression that had shown a hormetic response to AA would elevate the V_max value of SVCT-2, allowing more AA to accumulate. To evaluate the effects of magnesium on cancer cells, MgSO₄ and MgCl₂ were screened as magnesium supplements; both forms showed synergistic anticancer effects with AA. Taken together, the results of this study suggest that magnesium supplementation enhanced the anticancer effect of AA by inhibiting the hormetic response at a low dose. This study has also demonstrated that AA treatment with magnesium supplementation provided more effective anticancer therapy than AA treatment alone.