The enhancement of tumor radioresponse by combined treatment with cepharanthine is accompanied by the inhibition of DNA damage repair and the induction of apoptosis in oral squamous cell carcinoma

  • Authors:
    • Toyoko Harada
    • Koji Harada
    • Yoshiya Ueyama
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  • Published online on: May 31, 2012     https://doi.org/10.3892/ijo.2012.1501
  • Pages: 565-572
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Abstract

In the present study, we investigated whether treatment with cepharanthine, a biscoclaurine alkaloid extracted from Stephania cepharantha improves the response to radiotherapy in the oral squamous cell carcinoma (OSCC) cell lines, HSC2, HSC3 and HSC4. We examined the potential mechanisms that may contribute to the enhanced radiation response induced by cepharanthine. Growth inhibition was observed in vitro with radiation or cepharanthine. A co-operative anti-proliferative effect was obtained when cancer cells were treated with cepharanthine followed by radiation. Cepharanthine also promoted the mitotic death of 3 cell lines by radiation. The results from DNA damage repair analysis in the cultured OSCC cells demonstrated that cepharanthine had a strong inhibitory effect on DNA double-strand break (DSB) repair after radiation. The combined treatment of cepharanthine and radiation led to an increase in the sub-G1 peak as shown by flow cytometry, and markedly induced apoptosis through the activation of caspase-3. Tumor xenograft studies demonstrated that the combination of cepharanthine and radiation caused growth inhibition and tumor regression of OSCC tumors in athymic mice; tumor volume was reduced from 765.7 to 226.3 mm3 in HSC2 cells (p<0.01), 391.6 to 43.7 mm3 in HSC3 (p<0.01), and from 572.6 to 174.2 mm3 in HSC4 cells (p<0.01). In addition, combined therapy markedly increased tumor cell apoptosis. Overall, we conclude that cepharanthine enhances tumor radioresponse by multiple mechanisms that may involve the induction of apoptosis and the inhibition of DNA DSB repair after exposure to radiation.
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August 2012
Volume 41 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Harada T, Harada K and Ueyama Y: The enhancement of tumor radioresponse by combined treatment with cepharanthine is accompanied by the inhibition of DNA damage repair and the induction of apoptosis in oral squamous cell carcinoma. Int J Oncol 41: 565-572, 2012
APA
Harada, T., Harada, K., & Ueyama, Y. (2012). The enhancement of tumor radioresponse by combined treatment with cepharanthine is accompanied by the inhibition of DNA damage repair and the induction of apoptosis in oral squamous cell carcinoma. International Journal of Oncology, 41, 565-572. https://doi.org/10.3892/ijo.2012.1501
MLA
Harada, T., Harada, K., Ueyama, Y."The enhancement of tumor radioresponse by combined treatment with cepharanthine is accompanied by the inhibition of DNA damage repair and the induction of apoptosis in oral squamous cell carcinoma". International Journal of Oncology 41.2 (2012): 565-572.
Chicago
Harada, T., Harada, K., Ueyama, Y."The enhancement of tumor radioresponse by combined treatment with cepharanthine is accompanied by the inhibition of DNA damage repair and the induction of apoptosis in oral squamous cell carcinoma". International Journal of Oncology 41, no. 2 (2012): 565-572. https://doi.org/10.3892/ijo.2012.1501