A Chirality-dependent Action of Vitamin C in Suppressing Kirsten Rat Sarcoma Mutant Tumor Growth by the Oxidative Combination: Rationale for Cancer Therapeutics

Overview

Journal Int J Cancer

Specialty Oncology

Date 2019 Sep 1

PMID 31472018

Citations 6

Authors

Xinggang Wu

Mikyung Park

Dilara A Sarbassova

Haoqiang Ying

Min Gyu Lee

Rajat Bhattacharya

Lee Ellis

Christine B Peterson

Mien-Chie Hung

Hui-Kuan Lin

Rakhmetkazhi I Bersimbaev

Min Sup Song

Dos D Sarbassov

Affiliations

Soon will be listed here.

Abstract

Kirsten rat sarcoma (KRAS) mutant cancers, which constitute the vast majority of pancreatic tumors, are characterized by their resistance to established therapies and high mortality rates. Here, we developed a novel and extremely effective combinational therapeutic approach to target KRAS mutant tumors through the generation of a cytotoxic oxidative stress. At high concentrations, vitamin C (VC) is known to provoke oxidative stress and selectively kill KRAS mutant cancer cells, although its effects are limited when it is given as monotherapy. We found that the combination of VC and the oxidizing drug arsenic trioxide (ATO) is an effective therapeutic treatment modality. Remarkably, its efficiency is dependent on chirality of VC as its enantiomer d-optical isomer of VC (d-VC) is significantly more potent than the natural l-optical isomer of VC. Thus, our results demonstrate that the oxidizing combination of ATO and d-VC is a promising approach for the treatment of KRAS mutant human cancers.

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