Open Access

Induction of cell cycle arrest and apoptosis in myeloma cells by cepharanthine, a biscoclaurine alkaloid

  • Authors: Yoshitaka Kikukawa, Yutaka Okuno, Hiro Tatetsu, Miki Nakamura, Naoko Harada, Shikiko Ueno, Yorinori Kamizaki, Hiroaki Mitsuya, Hiroyuki Hata
  • View Affiliations

  • Published online on: Wednesday, October 1, 2008
  • Pages: 807-814
  • DOI: 10.3892/ijo_00000068

Abstract

Cepharanthine (CEP), a biscoclaurine alkaloid extracted from Stephania Cepharantha Hayata, has been used in Japan for treating patients with radiation-induced leucopenia or thrombocytopenia. We treated a patient with multiple myeloma (MM), who was not responding to preceding chemotherapy, who coincidently received therapy with CEP due to thrombocytopenia. Since the case showed a marked reduction of tumor load, direct anti-tumor effects of CEP to myeloma cells were investigated in vitro. Anti-tumor effects were observed in all myeloma cell lines tested, including a line resistant to melphalan. Exposure to CEP of a myeloma cell line induced the production of reactive oxygen species, activated the caspase-3 pathway and eventually induced apoptosis. Pre-exposure of cells to a pan-caspase inhibitor, Z-VAD-FMK, or a free radical scavenger, Tiron, effectively blocked CEP-induced apoptosis. Interestingly, CEP also inhibited cell growth of myeloma cells by inducing CDK inhibitors. These data show, for the first time, that CEP has anti-myeloma effects by the activation of apoptotic pathways and blocking cell cycle progression via CDK inhibitors. Although analysis of these two pathways should be clarified further, the use of CEP may be considered as a potential therapeutic agent for a subset of MM.
Journal Cover

October 2008
Volume 33 Issue 4

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

2013 Impact Factor: 2.773
Ranked #30/202 Oncology
(total number of cites)

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APA
Kikukawa, Y., Okuno, Y., Tatetsu, H., Nakamura, M., Harada, N., Ueno, S., Kamizaki, Y., Mitsuya, H., & Hata, H. (2008). Induction of cell cycle arrest and apoptosis in myeloma cells by cepharanthine, a biscoclaurine alkaloid. International Journal of Oncology, 33(4), 807-814.
MLA
Kikukawa, Okuno, Tatetsu, Nakamura, Harada, Ueno, Kamizaki, Mitsuya, and Hiroyuki Hata. "Induction of cell cycle arrest and apoptosis in myeloma cells by cepharanthine, a biscoclaurine alkaloid." International Journal of Oncology International Journal of Oncology 33.4 (2008): 807-814.
Chicago
Kikukawa, Okuno, Tatetsu, Nakamura, Harada, Ueno, Kamizaki, Mitsuya, and Hiroyuki Hata. "Induction of cell cycle arrest and apoptosis in myeloma cells by cepharanthine, a biscoclaurine alkaloid." International Journal of Oncology International Journal of Oncology 33 no. 4 (2008): 807-814.