Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models

  • Authors:
    • Tsutomu Takahashi
    • Yoshio Honma
    • Takaaki Miyake
    • Koji Adachi
    • Saki Takami
    • Masahiro Okada
    • Satoshi Kumanomidou
    • Fumiyoshi Ikejiri
    • Yumi Jo
    • Chie Onishi
    • Koshi Kawakami
    • Ichiro Moriyama
    • Masaya Inoue
    • Junko Tanaka
    • Junji Suzumiya
  • View Affiliations

  • Published online on: February 9, 2015     https://doi.org/10.3892/ijo.2015.2882
  • Pages: 1801-1809
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Multiple myeloma is a malignant proliferative disease of plasma cells in the bone marrow and remains largely incurable. Cotylenin A, a fusicoccane diterpene glycoside with a complex sugar moiety, was isolated as a plant-growth regulator. Cotylenin A has been shown to inhibit the growth of various cancer cells. Herein, we examined the anti-myeloma effects of cotylenin A using five human myeloma cell lines (RPMI-8226, KMS-11, KMS-26, KMS-12 PE and KMS-12 BM) and xenografts in immunodeficient mice. Cotylenin A and vincristine synergistically inhibited the growth and induced apoptosis in myeloma cells. While other microtubule-disturbing agents also showed co-operative effects with cotylenin A, other anticancer agents, such as doxorubicin, cisplatin, camptothecin, methotrexate, gemcitabine and 5-fluorouracil, did not show such co-operation with cotylenin A. These differences might be attributed to the effects on autophagic responses. Combined treatment with cotylenin A and vincristine induced autophagy (formation of LC3-II and degradation of p62 protein). However, doxorubicin did not enhance the autophagy induced by cotylenin A. A colony-forming assay indicated that the combined treatment with cotylenin A and vincristine more effectively suppressed the formation of large colonies, which have higher self-renewal activity than vincristine alone. Expression of pluripotency-associated transcription factor Sox2 mRNA in RPMI-8226 myeloma cells was significantly suppressed by treatment with cotylenin A. Combined treatment with cotylenin A and vincristine significantly inhibited the growth of KMS-26 myeloma cells as xenografts. Our results suggest that the combination of cotylenin A and vincristine may have therapeutic value. Recently, it was reported that cotylenin A modulates the 14-3-3 intracellular signaling pathway. The 14-3-3 proteins may be novel targets in treating myeloma. However, our study could not explain how the sensitization to vincristine is related to the effects of cotylenin A on the 14-3-3 signaling pathway and further studies will be needed.
View Figures
View References

Related Articles

Journal Cover

April-2015
Volume 46 Issue 4

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Takahashi T, Honma Y, Miyake T, Adachi K, Takami S, Okada M, Kumanomidou S, Ikejiri F, Jo Y, Onishi C, Onishi C, et al: Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models. Int J Oncol 46: 1801-1809, 2015
APA
Takahashi, T., Honma, Y., Miyake, T., Adachi, K., Takami, S., Okada, M. ... Suzumiya, J. (2015). Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models. International Journal of Oncology, 46, 1801-1809. https://doi.org/10.3892/ijo.2015.2882
MLA
Takahashi, T., Honma, Y., Miyake, T., Adachi, K., Takami, S., Okada, M., Kumanomidou, S., Ikejiri, F., Jo, Y., Onishi, C., Kawakami, K., Moriyama, I., Inoue, M., Tanaka, J., Suzumiya, J."Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models". International Journal of Oncology 46.4 (2015): 1801-1809.
Chicago
Takahashi, T., Honma, Y., Miyake, T., Adachi, K., Takami, S., Okada, M., Kumanomidou, S., Ikejiri, F., Jo, Y., Onishi, C., Kawakami, K., Moriyama, I., Inoue, M., Tanaka, J., Suzumiya, J."Synergistic combination therapy with cotylenin A and vincristine in multiple myeloma models". International Journal of Oncology 46, no. 4 (2015): 1801-1809. https://doi.org/10.3892/ijo.2015.2882