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Int J Oncol. 2017 Feb;50(2):387-395. doi: 10.3892/ijo.2016.3821. Epub 2016 Dec 28.

Induced overexpression of CD44 associated with resistance to apoptosis on DNA damage response in human head and neck squamous cell carcinoma cells.

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Department of Natural and Medicinal Chemistry, Faculty of Pharmaceutical Sciences Aomori University, Aomori, Aomori 030-0943, Japan.
Department of Oral Biochemistry, Asahi University School of Dentistry, Gifu 501-0296, Japan.


CD44 is a marker of cancer stem cells in head and neck squamous cell carcinoma, and CD44 expression is related to prognosis in cancer patients. We examined whether herbal medicine components affect CD44 expression and induce cancer cell apoptosis. Baicalin enhanced apoptosis with no effect on CD44 levels, while baicalein did not enhance apoptosis and upregulated CD44 in head and neck squamous cell carcinoma. Furthermore, baicalein induced phosphorylation of CHK1, as a marker of DNA damage response to S-to-G2/M phase arrest. Our results clearly demonstrated that baicalein enhanced expression of CD44 and accordingly enhanced the DNA damage response. These data suggest that induction of CD44 inhibited cancer cell induction of apoptosis by increasing the DNA damage response. Together, our findings suggest that CD44 expression in head and neck squamous cell carcinoma plays a role in enhancing the DNA damage response.

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