Cristazine, a novel dioxopiperazine alkaloid, induces apoptosis via the death receptor pathway in A431 cells

Autor: Yong Bae Seo, Han Kyu Lim, Maheshkumar Prakash Patil, Byeng Wha Son, Mi Jeong Jo, Gun-Do Kim, Hyun Il Jung
Rok vydání: 2019
Předmět:
Zdroj: Drug Development Research. 80:504-512
ISSN: 1098-2299
0272-4391
DOI: 10.1002/ddr.21527
Popis: The fungus Chaetomium sp. is a causative agent of infections in humans and is ubiquitous in the natural environment. The secondary metabolites of this genus exhibit many biological activities, including antifungal activity and toxicity in mitochondria. In this study, we isolated cristazine from the fungus C. cristatum, which has the potential to inhibit the growth of human epidermoid carcinoma (A431) cells in a dose- and time-dependent manner. Its inhibitory activity was examined using a cell viability assay and cell death was elucidated by western blot analysis. Cristazine triggered apoptotic cell death via the Type I death receptor pathway including the activation of caspases and other target proteins. However, cristazine did not have any effect on mitochondrial apoptotic proteins such as Bid, cytochrome c, and apoptosis-inducing factor. Cristazine inhibited the cell cycle progression by arresting the G1 /S phase and up-regulating the inhibitory proteins of cyclin-dependent kinases. Thus, cristazine has great potential for inducing apoptosis in A431 cells via both cell cycle arrest and the inhibition of cell growth.
Databáze: OpenAIRE