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- Title
Stellettin B-Induced Oral Cancer Cell Death via Endoplasmic Reticulum Stress–Mitochondrial Apoptotic and Autophagic Signaling Pathway.
- Authors
Kuo, Tsu-Jen; Jean, Yen-Hsuan; Shih, Po-Chang; Cheng, Shu-Yu; Kuo, Hsiao-Mei; Lee, Yi-Ting; Lai, Yu-Cheng; Tseng, Chung-Chih; Chen, Wu-Fu; Wen, Zhi-Hong
- Abstract
Oral squamous cell carcinoma (OSCC) affects tens of thousands of people worldwide. Despite advances in cancer treatment, the 5-year survival rate of patients with late-stage OSCC is low at 50–60%. Therefore, the development of anti-OSCC therapy is necessary. We evaluated the effects of marine-derived triterpene stellettin B in human OC2 and SCC4 cells. Stellettin B dose-dependently decreased the viability of both cell lines, with a significant reduction in OC2 cells at ≥0.1 µM at 24 and 48 h, and in SCC4 cells at ≥1 µM at 24 and 48 h. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells were significantly observed at 20 µM of stellettin B at 48 h, with the overexpression of cleaved caspase3 and cleaved poly(ADP-ribose) polymerase (PARP). Moreover, mitochondrial respiratory functions were ablated by stellettin B. Autophagy-related LC3-II/LC3-I ratio and Beclin-1 proteins were increased, whereas p62 was decreased. At 20 µM at 48 h, the expression levels of the endoplasmic reticulum (ER) stress biomarkers calnexin and BiP/GRP78 were significantly increased and mitogen-activated protein kinase (MAPK) signaling pathways were activated. Further investigation using the autophagy inhibitor 3-methyladenine (3-MA) demonstrated that it alleviated stellettin B-induced cell death and autophagy. Overall, our findings show that stellettin B induces the ER stress, mitochondrial stress, apoptosis, and autophagy, causing cell death of OSCC cells.
- Subjects
CELL death; ENDOPLASMIC reticulum; TRITERPENES; CANCER cells; ORAL cancer; CELLULAR signal transduction; MITOGEN-activated protein kinases; POLY ADP ribose
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 15, p8813
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23158813