Deoxyshikonin Mediates Heme Oxygenase-1 Induction and Apoptotic Response via p38 Signaling in Tongue Cancer Cell Lines

Deoxyshikonin (DSK), a phytochemical constituent, has been documented to elicit various oncostatic properties alone or in combination with established therapeutics. However, its role in restraining oral squamous cell carcinoma (OSCC) is mostly unclear. Here, we examined the tumor-suppressive effect...

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Bibliographic Details
Main Authors: Chun-Yi Chuang, Chiao-Wen Lin, Chun-Wen Su, Yi-Tzu Chen, Wei-En Yang, Shun-Fa Yang, Shih-Chi Su
Format: Article
Language:English
Published: MDPI AG 2022-06-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/23/13/7115
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Summary:Deoxyshikonin (DSK), a phytochemical constituent, has been documented to elicit various oncostatic properties alone or in combination with established therapeutics. However, its role in restraining oral squamous cell carcinoma (OSCC) is mostly unclear. Here, we examined the tumor-suppressive effect of DSK and explored the molecular mechanisms underlying DSK’s activities on controlling oral cancer. Our results showed that DSK dose-dependently lessened the cell viability of tongue cancer cell lines, involving induction of cell cycle arrest at the sub-G1 phase and apoptotic cell death. Moreover, a unique signature of apoptosis-related proteins, including augmented nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) expression and caspase activation, was observed in DSK-treated tongue cancer cell lines. Furthermore, DSK-mediated upregulation of HO-1 and cleavage of caspase-9 and -3 were significantly inhibited by pharmacological blockage of p38 kinase. Collectively, these data revealed that DSK halted cell cycle progression and elicited cell apoptosis in tongue cancer cell lines, reshaping a p38-dependent profile of apoptotic proteome. Our findings provided novel insights into the therapeutic implications of a natural compound on the management of OSCC.
ISSN:1661-6596
1422-0067