Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression

Sungrae Cho; Jin Sung Chae; Hocheol Shin; Yujeong Shin; Haeun Song; Youngwook Kim; Byong Chul Yoo; Kangsan Roh; Seungchan Cho; Eui joon Kil; Hee seong Byun; Sang ho Cho; Seyeon Park; Sukchan Lee; Chang Hwan Yeom

doi:10.1038/s41598-018-29386-7

Hormetic dose response to _L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression

Sungrae Cho
, Jin Sung Chae
, Hocheol Shin
, Yujeong Shin
, Haeun Song
, Youngwook Kim
, Byong Chul Yoo
, Kangsan Roh
, Seungchan Cho
, Eui joon Kil
, Hee seong Byun
, Sang ho Cho
, Seyeon Park
, Sukchan Lee
, Chang Hwan Yeom

Department of Integrative Biotechnology

Sungkyunkwan University
Yeom Chang-Hwan Hospital
Dongduk Women's University
National Cancer Center Korea

Research output: Contribution to journal › Article › peer-review

59 Scopus citations

Abstract

_L-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of _L-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of _L-ascorbic acid. In this study, we demonstrate that _L-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of _L-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose _L-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose _L-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of _L-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that _L-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.

Original language	English
Article number	11372
Journal	Scientific Reports
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41598-018-29386-7
State	Published - 1 Dec 2018

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10.1038/s41598-018-29386-7

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Cho, S., Chae, J. S., Shin, H., Shin, Y., Song, H., Kim, Y., Yoo, B. C., Roh, K., Cho, S., Kil, E. J., Byun, H. S., Cho, S. H., Park, S., Lee, S., & Yeom, C. H. (2018). Hormetic dose response to _L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression. Scientific Reports, 8(1), Article 11372. https://doi.org/10.1038/s41598-018-29386-7

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title = "Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression",

abstract = "L-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of L-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of L-ascorbic acid. In this study, we demonstrate that L-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of L-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose L-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose L-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of L-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that L-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.",

author = "Sungrae Cho and Chae, \{Jin Sung\} and Hocheol Shin and Yujeong Shin and Haeun Song and Youngwook Kim and Yoo, \{Byong Chul\} and Kangsan Roh and Seungchan Cho and Kil, \{Eui joon\} and Byun, \{Hee seong\} and Cho, \{Sang ho\} and Seyeon Park and Sukchan Lee and Yeom, \{Chang Hwan\}",

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AU - Cho, Sungrae

AU - Chae, Jin Sung

AU - Shin, Hocheol

AU - Shin, Yujeong

AU - Song, Haeun

AU - Kim, Youngwook

AU - Yoo, Byong Chul

AU - Roh, Kangsan

AU - Cho, Seungchan

AU - Kil, Eui joon

AU - Byun, Hee seong

AU - Cho, Sang ho

AU - Park, Seyeon

AU - Lee, Sukchan

AU - Yeom, Chang Hwan

PY - 2018/12/1

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N2 - L-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of L-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of L-ascorbic acid. In this study, we demonstrate that L-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of L-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose L-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose L-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of L-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that L-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.

AB - L-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of L-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of L-ascorbic acid. In this study, we demonstrate that L-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of L-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose L-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose L-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of L-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that L-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.

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ER -

Hormetic dose response to _L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression

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