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

Dynamin-related protein 1 (Drp1) mediates mitochondrial fission. Recently, several studies have shown that Drp1 plays an important role in some cancers. However, little is known about Drp1 in cutaneous squamous cell carcinoma (SCC).. To investigate the role of Drp1 in the tumorigenesis of cutaneous SCCs.. We investigated cell proliferation, cell cycle, mitochondrial morphology, and MAPK signaling pathway using cutaneous SCC A431 and DJM1 cells that were transfected with shRNA vectors targeting Drp1. The Drp1 gene-knockdown SCC cells showed lower cell proliferation than scramble-control cells, as assessed by direct cell counting and clonogenic assays. DNA content analysis showed Drp1 knockdown to cause G2/M arrest. Morphologically, the depletion of Drp1 resulted in an elongated, hyper-fused mitochondrial network. The MEK inhibitor PD325901 suppressed cell proliferation, as well as inhibiting the phosphorylation of ERK. Our results reveal a crucial function for Drp1 in regulating tumor growth, mitochondrial morphology, and cell cycle in cutaneous SCC, suggesting that Drp1 could be a novel target for skin tumor therapies.

Topics: Aged; Aged, 80 and over; Animals; Benzamides; Carcinogenesis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Proliferation; Diphenylamine; Dynamins; Female; G2 Phase Cell Cycle Checkpoints; Gene Knockdown Techniques; GTP Phosphohydrolases; Humans; Male; MAP Kinase Signaling System; Mice; Mice, Inbred BALB C; Mice, Nude; Microtubule-Associated Proteins; Middle Aged; Mitochondria; Mitochondrial Dynamics; Mitochondrial Proteins; Neoplasm Staging; Phosphorylation; Quinazolinones; RNA Interference; RNA, Small Interfering; Skin Neoplasms; Xenograft Model Antitumor Assays