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N-alkyl triphenylvinylpyridinium conjugated dihydroartemisinin perturbs mitochondrial functions resulting in enhanced cancer versus normal cell toxicity.
Varmazyad, Mahboubeh; Modi, Mira M; Kalen, Amanda L; Sarsour, Ehab H; Wagner, Brett; Du, Juan; Schultz, Michael K; Buettner, Garry R; Pigge, F Christopher; Goswami, Prabhat C.
Afiliación
  • Varmazyad M; Department of Chemistry, University of Iowa, Iowa City, IA, 52242, USA.
  • Modi MM; Basic Science Department, College of Osteopathic Medicine, Kansas City University, Kansas City, MO, 64106, USA.
  • Kalen AL; Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IA, 52242, USA.
  • Sarsour EH; Basic Science Department, College of Osteopathic Medicine, Kansas City University, Kansas City, MO, 64106, USA.
  • Wagner B; Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IA, 52242, USA.
  • Du J; Department of Surgery, University of Iowa, Iowa City, IA, 52242, USA.
  • Schultz MK; Department of Radiology, University of Iowa, Iowa City, IA, 52242, USA.
  • Buettner GR; Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IA, 52242, USA.
  • Pigge FC; Department of Chemistry, University of Iowa, Iowa City, IA, 52242, USA.
  • Goswami PC; Free Radical and Radiation Biology Division, Department of Radiation Oncology, University of Iowa, Iowa City, IA, 52242, USA. Electronic address: prabhat-goswami@uiowa.edu.
Free Radic Biol Med ; 165: 421-434, 2021 03.
Article en En | MEDLINE | ID: mdl-33561488
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artemisininas / Neoplasias / Antimaláricos Límite: Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Artemisininas / Neoplasias / Antimaláricos Límite: Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos