Enhancement of hypoxia-induced apoptosis of human breast cancer cells via STAT5b by momilactone B

  • Authors:
    • Youn-Hee Joung
    • Eun-Joung Lim
    • Mi-Sun Kim
    • So Dug Lim
    • So-Young Yoon
    • Young Chang Lim
    • Young Bum Yoo
    • Sang-Kyu Ye
    • Taekyu Park
    • Ill-Min Chung
    • Ki-Yeol Bae
    • Young Mok Yang
  • View Affiliations

  • Published online on: September 1, 2008     https://doi.org/10.3892/ijo_00000030
  • Pages: 477-484
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Abstract

We have shown previously that hypoxia activates the cyclin D1 promoter via the Jak2/STAT5b pathway in breast cancer cells. Most solid tumors contain hypoxic components and overexpression of cyclin D1. The purpose of the present study was to investigate the molecular mechanism by which momilactone B exerts its inhibitory effects on breast cancer cells. Momilactone B, extracted from Korean rice hulls, suppressed hypoxia-induced increases in phospho-STAT5, STAT5b, cyclin D1, and cdk4 protein levels in human breast cancer cells. STAT5b expression was inhibited by siRNA experiments leading to decreased cyclin D1. The effects of momilactone B on cell growth and apoptosis-related gene expression were investigated in breast cancer cells under hypoxic conditions (2% O2). Bax and p21 expression was found to be up-regulated, whereas ppRb and bcl-2 were down-regulated in momilactone B-treated cells under hypoxic conditions. However, the p53 protein level did not change. Flow cytometry with Annexin-FITC staining showed that the number of apoptotic cells increased in hypoxic cells treated with momilactone B compared with untreated hypoxic cells. Furthermore, caspase activity increased upon treatment with momilactone B under hypoxic conditions. These results indicate that momilactone B inhibits the growth of breast cancer cells, regulates the expression of apoptosis-related genes, and induces apoptosis through STAT5b and a caspase-3 dependent pathway. We suggest that momilactone B accelerates hypoxia-induced apoptosis of human breast cancer cells through STAT5b, and may represent an effective chemopreventive or therapeutic agent against breast cancer.

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September 2008
Volume 33 Issue 3

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

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Spandidos Publications style
Joung Y, Lim E, Kim M, Lim SD, Yoon S, Lim YC, Yoo YB, Ye S, Park T, Chung I, Chung I, et al: Enhancement of hypoxia-induced apoptosis of human breast cancer cells via STAT5b by momilactone B. Int J Oncol 33: 477-484, 2008.
APA
Joung, Y., Lim, E., Kim, M., Lim, S.D., Yoon, S., Lim, Y.C. ... Yang, Y.M. (2008). Enhancement of hypoxia-induced apoptosis of human breast cancer cells via STAT5b by momilactone B. International Journal of Oncology, 33, 477-484. https://doi.org/10.3892/ijo_00000030
MLA
Joung, Y., Lim, E., Kim, M., Lim, S. D., Yoon, S., Lim, Y. C., Yoo, Y. B., Ye, S., Park, T., Chung, I., Bae, K., Yang, Y. M."Enhancement of hypoxia-induced apoptosis of human breast cancer cells via STAT5b by momilactone B". International Journal of Oncology 33.3 (2008): 477-484.
Chicago
Joung, Y., Lim, E., Kim, M., Lim, S. D., Yoon, S., Lim, Y. C., Yoo, Y. B., Ye, S., Park, T., Chung, I., Bae, K., Yang, Y. M."Enhancement of hypoxia-induced apoptosis of human breast cancer cells via STAT5b by momilactone B". International Journal of Oncology 33, no. 3 (2008): 477-484. https://doi.org/10.3892/ijo_00000030