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Mechanistic Investigation of the Specific Anticancer Property of Artemisinin and Its Combination with Aminolevulinic Acid for Enhanced Anticolorectal Cancer Activity.

Wang, J; Zhang, J; Shi, Y; Xu, C; Zhang, C; Wong, YK; Lee, YM; Krishna, S; He, Y; Lim, TK; et al. Wang, J; Zhang, J; Shi, Y; Xu, C; Zhang, C; Wong, YK; Lee, YM; Krishna, S; He, Y; Lim, TK; Sim, W; Hua, Z-C; Shen, H-M; Lin, Q (2017) Mechanistic Investigation of the Specific Anticancer Property of Artemisinin and Its Combination with Aminolevulinic Acid for Enhanced Anticolorectal Cancer Activity. ACS Cent Sci, 3 (7). pp. 743-750. ISSN 2374-7943 https://doi.org/10.1021/acscentsci.7b00156
SGUL Authors: Krishna, Sanjeev

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Abstract

The antimalarial artemisinin (ART) possesses anticancer activity, but its underlying mechanism remains largely unclear. Using a chemical proteomics approach with artemisinin-based activity probes, we identified over 300 specific ART targets. This reveals an anticancer mechanism whereby ART promiscuously targets multiple critical biological pathways and leads to cancer cell death. The specific cytotoxicity of ART against colorectal cancer (CRC) cells rather than normal colon epithelial cells is due to the elevated capacity of heme synthesis in the cancer cells. Guided by this mechanism, the specific cytotoxicity of ART toward CRC cells can be dramatically enhanced with the addition of aminolevulinic acid (ALA), a clinically used heme synthesis precursor, to increase heme levels. Importantly, this novel ART/ALA combination therapy proves to be more effective than an ART monotherapy in a mouse xenograft CRC model. Thus, ART can be repurposed and potentiated by exploitation of its mechanism of action and the metabolic features of the CRC cells.

Item Type: Article
Additional Information: ACS AuthorChoice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: ACS Cent Sci
ISSN: 2374-7943
Language: eng
Dates:
DateEvent
26 July 2017Published
28 June 2017Published Online
14 June 2017Accepted
Projects:
Project IDFunderFunder ID
NMRC/CIRG/1373/2013National Medical Research Councilhttp://dx.doi.org/10.13039/501100001349
81630092Chinese National Natural Sciences FoundationUNSPECIFIED
81421091Chinese National Natural Sciences FoundationUNSPECIFIED
20130091130003Doctoral Station Science FoundationUNSPECIFIED
PubMed ID: 28776016
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/109042
Publisher's version: https://doi.org/10.1021/acscentsci.7b00156

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