Document Type
Article
Publication Title
Free Radical Biology and Medicine
Abstract
Dihydroartemisinin (DHA) is an FDA-approved antimalarial drug that has been repurposed for cancer therapy because of its preferential antiproliferative effects on cancer versus normal cells. Mitochondria represent an attractive target for cancer therapy based on their regulatory role in proliferation and cell death. This study investigates whether DHA conjugated to innately fluorescent N-alkyl triphenylvinylpyridinium (TPVP) perturbs mitochondrial functions resulting in a differential toxicity of cancer versus normal cells. TPVP-DHA treatments resulted in a dose-dependent toxicity of human melanoma and pancreatic cancer cells, whereas normal human fibroblasts were resistant to this treatment. TPVP-DHA treatments resulted in a G1-delay of the cancer cell cycle, which was also associated with a significant inhibition of the mTOR-metabolic and ERK1/2-proliferative signaling pathways. TPVP-DHA treatments perturbed mitochondrial functions, which correlated with increases in mitochondrial fission. In summary, TPVP mediated mitochondrial targeting of DHA enhanced cancer cell toxicity by perturbing mitochondrial functions and morphology.
DOI
10.1016/j.freeradbiomed.2021.01.050
Publication Date
3-2021
Keywords
Dihydroartemisinin, ERK1/2, melanoma, mitochondria-fission, mitochondria-targeted DHA, N-alkyl triphenylvinylpyridinium, pancreatic cancer, mTOR
ISSN
0891-5849
Recommended Citation
Varmazyad M, Modi MM, Kalen AL, Sarsour E, Wagner B, Du J, Schultz MK, Buettner GR, Pigge FC, Goswami P. N-Alkyl Triphenylvinylpyridinium Conjugated Dihydroartemisinin Perturbs Mitochondrial Functions Resulting in Enhanced Cancer Versus Normal Cell Toxicity. Free Radical Biology and Medicine. 2021; 165. doi: 10.1016/j.freeradbiomed.2021.01.050.
