期刊
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
卷 138, 期 -, 页码 427-434出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2013.09.002
关键词
Proliferation; Cell cycle; Head and neck cancer; Vitamin D analog; SCC; MART-10
资金
- Chang Gung Memorial Hospital Research Grant (CMRPG) [2A0322]
- CMRPG [290491, 290492, 290493]
- National Science Council, Republic of China [NSC102-2320-B-182-003-MY3]
- CTSA grant from NIH [UL1-TR000157]
For the head and neck squamous cell carcinoma (HNSCC), surgery in combination with radiation therapy is the current standard treatment. However, the complex anatomy and important functions over the head and neck region often make HNSCC patients with severe comorbidities. Even after aggressive treatment, the 5 year survival for HNSCC patients is only around 61%. Thus, new therapeutic regimens against HNSCC are urgently needed. 1 alpha,25-Dihydroxyvitamin D-3 [1 alpha,25(OH)(2)D-3] is a potent anti-tumor agent in a variety of pre-clinical studies, but its clinical application is impeded by hypercalcemic side effect. A new class of less-calcemic 1 alpha,25(OH)(2)D-3 analog, MART-10 (19-nor-2 alpha-(3-hydroxypropy1)- 1 alpha,25-Dihydroxyvitamin D-3), has been shown to be much more potent than 1 alpha,25(OH)(2)D-3 in inhibiting cancer cell growth in vitro and in vivo without inducing hypercalcemia. In this study, we compared the antiproliferative activity of MART-10 with 1 alpha,25(OH)(2)D-3 and the mechanism responsible for the inhibition in FaDu and SCC-25 squamous carcinoma cells. Our results demonstrate that MART-10 is more potent than 1 alpha,25(OH)(2)D-3 in suppressing FaDu and SCC-25 cell growth through greater cell cycle arrest at G(0)/G(1), accompanied by a greater downregulation of ki-67 expression and upregulation of p21 and p27. We also showed that telomerase expression in SCC-25 was suppressed to a greater extent by MART-10 than by 1 alpha,25(OH)(2)D-3. Thus, given the previously-proven in vivo antitumor effect and safety of MART-10 and bleak background of HNSCC, based on our current result, we concluded that MART-10 has a potential as a chemo-preventive and - therapeutic agent to treat HNSCC. (C) 2013 Elsevier Ltd. All rights reserved.
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