3-(2-4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3h)-quinazolinone and Breast-Neoplasms

Overactive mitochondrial fission was shown to promote cell transformation and tumor growth. It remains elusive how mitochondrial quality is regulated in such conditions. Here, we show that upregulation of mitochondrial fission protein, dynamin related protein-1 (Drp1), was accompanied with increased mitochondrial biogenesis markers (PGC1

Topics: Autophagy; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Dynamins; Gene Expression Regulation, Neoplastic; GTP Phosphohydrolases; Humans; Microtubule-Associated Proteins; Mitochondria; Mitochondrial Proteins; Organelle Biogenesis; Oxidation-Reduction; Quinazolinones; RNA, Messenger; Up-Regulation

Mitochondria are high dynamic organelles with frequent fission and fusion. Here, we found hypoxia stimulated Drp1 expression, mitochondrial fission and migration in metastatic MDA-MB‑231 cells, but not in non-metastatic MCF-7 cells. Inhibition of Drp1-dependent mitochondrial fission by Mdivi-1 or silencing Drp1 attenuated hypoxia-induced mitochondrial fission and migration in MDA-MB‑231 cells. On the other hand, cisplatin induced significant apoptosis and mitochondrial fission in MDA-MB‑231 cells, but not in MCF-7 cells. Mdivi-1 and silencing Drp1 also efficiently prevented cisplatin-induced MMP decrease, ROS production and apoptosis in MDA-MB‑231 cells. Our data suggest that Drp1-dependent mitochondrial fission not only regulates hypoxia-induced migration of breast cancer cells, but also facilitates its sensitivity to chemotherapeutic agents. Thus, targeting Drp1-dependent mitochondrial dynamics may provide a novel strategy to suppress breast cancer metastasis and improve the chemotherapeutic effect in the future.

Topics: Apoptosis; Breast Neoplasms; Cell Hypoxia; Cell Movement; Cisplatin; Dynamins; Female; GTP Phosphohydrolases; Humans; MCF-7 Cells; Microtubule-Associated Proteins; Mitochondrial Dynamics; Mitochondrial Proteins; Quinazolinones