A chirality-dependent action of vitamin C in suppressing Kirsten rat sarcoma mutant tumor growth by the oxidative combination: Rationale for cancer therapeutics

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2822-2828
Number of pages7
JournalInternational Journal of Cancer
Volume146
Issue number10
DOIs
StatePublished - May 15 2020

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Keywords

  • Kirsten rat sarcoma mutant cancer cells
  • apoptosis
  • drug combination
  • oxidative stress
  • reactive oxygen species

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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