Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells

  • Authors:
    • Chi Man Tsang
    • Echo Ping Woi Lau
    • Kaijun Di
    • Pak Yan Cheung
    • Pok Man Hau
    • Yick Pang Ching
    • Yong Chuan Wong
    • Annie Lai Man Cheung
    • Thomas S.K. Wan
    • Yao Tong
    • Sai Wah Tsao
    • Yibin Feng
  • View Affiliations

  • Published online on: July 1, 2009     https://doi.org/10.3892/ijmm_00000216
  • Pages: 131-138
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Abstract

Berberine is an active ingredient extracted from Coptidis rhizoma which has been used for centuries as a traditional Chinese medicine for treatment of inflammatory diseases. Recent studies have indicated that berberine has anticancer properties. Berberine arrested cell growth and inhibited cell migration in various cancer cell lines. In this study, we examined the effects of berberine on HONE1 cells, which have been commonly used as a cell model for nasopharyngeal carcinoma. We observed the inhibitory effects of berberine on HONE1 cells at a high dosage (>150 µM). Berberine effectively induced the mitotic arrest of HONE1 cells at 300 µM which was associated with apoptosis. Berberine had differential intracellular localization at low and high doses. At a low dose (50 µM), berberine was localized in the mitochondria while at a high dose (300 µM), berberine was localized in the nucleus which may have induced mitotic arrest. Berberine effectively inhibited cell migration and invasion at low doses. Using a specific GST pull-down assay of activated Rho GTPases, we demonstrated that berberine suppressed the activation of Rho GTPases including RhoA, Cdc42 and Rac1. This indicates a novel function of berberine in the suppression of Rho GTPase signaling to mediate its inhibitory action on cell migration and motility. The potential of berberine to inhibit cancer metastasis in cancer warrants further investigation.

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July 2009
Volume 24 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Tsang CM, Lau EP, Di K, Cheung PY, Hau PM, Ching YP, Wong YC, Cheung AL, Wan TS, Tong Y, Tong Y, et al: Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells. Int J Mol Med 24: 131-138, 2009
APA
Tsang, C.M., Lau, E.P., Di, K., Cheung, P.Y., Hau, P.M., Ching, Y.P. ... Feng, Y. (2009). Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells. International Journal of Molecular Medicine, 24, 131-138. https://doi.org/10.3892/ijmm_00000216
MLA
Tsang, C. M., Lau, E. P., Di, K., Cheung, P. Y., Hau, P. M., Ching, Y. P., Wong, Y. C., Cheung, A. L., Wan, T. S., Tong, Y., Tsao, S. W., Feng, Y."Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells". International Journal of Molecular Medicine 24.1 (2009): 131-138.
Chicago
Tsang, C. M., Lau, E. P., Di, K., Cheung, P. Y., Hau, P. M., Ching, Y. P., Wong, Y. C., Cheung, A. L., Wan, T. S., Tong, Y., Tsao, S. W., Feng, Y."Berberine inhibits Rho GTPases and cell migration at low doses but induces G2 arrest and apoptosis at high doses in human cancer cells". International Journal of Molecular Medicine 24, no. 1 (2009): 131-138. https://doi.org/10.3892/ijmm_00000216