Bromelain effectively suppresses Kras-mutant colorectal cancer by stimulating ferroptosis

Autor: Sujeong Park, Jinjoo Oh, Minhee Kim, Eun-Jung Jin
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Zdroj: Animal Cells and Systems, Vol 22, Iss 5, Pp 334-340 (2018)
Druh dokumentu: article
ISSN: 1976-8354
2151-2485
19768354
DOI: 10.1080/19768354.2018.1512521
Popis: Here, we investigated the possible anti-cancer properties of bromelain in Kras mutant human colorectal carcinoma cell lines and a mouse model harboring a Kras mutation. Cell growth and proliferation were significantly reduced in the Kras mutant colorectal carcinoma cell lines following treatment with 50 μg/mL bromelain as assessed by crystal violet staining and a proliferation assay. To identify the molecules responsible for this action, the expression levels of genes involved in signaling pathways and miRNAs were analyzed by real-time PCR. Among the genes tested, down-regulation of ACSL-4 and up-regulation of miRNAs targeting ASCL-4 were observed in Caco2 cells. Compared to the Kras wild-type colorectal carcinoma cell lines, Kras mutant colorectal carcinoma cell lines exhibited a remarkably up-regulated expression of ACSL-4, which is responsible for ferroptosis sensitivity. Moreover, the knockdown of ACSL-4 by a specific shRNA inhibited erastin-induced ferroptosis in Kras mutant DLD-1 cells as assessed by propidium iodide staining and lipid reactive oxygen species measurement. Our findings indicate that bromelain effectively exerts cytotoxic effects in Kras mutant colorectal cancer cells compared to in Kras wild-type colorectal cancer cells. Differential expression of ACSL-4 is responsible for the differential action of bromelain in regulating ferroptotic cell death.
Databáze: Directory of Open Access Journals
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