A CHIRALITY-DEPENDENT ACTION OF VITAMIN C IN SUPPRESSINGKIRSTEN RAT SARCOMA MUTANT TUMOR GROWTH BY THE OXIDATIVECOMBINATION: RATIONALE FOR CANCER THERAPEUTICS
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Date
2019-08-31
Authors
Wu, Xinggang
Park, Mikyung
Sarbassova, Dilara A.
Ying, Haoqiang
Lee, Min Gyu
Bhattacharya, Rajat
Ellis, Lee
Peterson, Christine B.
Hung, Mien-Chie
Lin, Hui-Kuan
Journal Title
Journal ISSN
Volume Title
Publisher
International Journal of Cancer
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
Description
Keywords
Type of access: Open Access, Kirsten rat sarcoma
Citation
Wu, X., Park, M., Sarbassova, D. A., Ying, H., Lee, M. G., Bhattacharya, R., Ellis, L., Peterson, C. B., Hung, M., Lin, H., Bersimbaev, R. I., Song, M. S., & Sarbassov, D. D. (2020). A chirality‐dependent action of vitamin C in suppressing Kirsten rat sarcoma mutant tumor growth by the oxidative combination: Rationale for cancer therapeutics. International Journal of Cancer, 146(10), 2822–2828. https://doi.org/10.1002/ijc.32658