Involvement of the mitochondrial pathway in bruceine D-induced apoptosis in Capan-2 human pancreatic adenocarcinoma cells

  • Authors:
    • Ling Liu
    • Zhi-Xiu Lin
    • Po Sing Leung
    • Li-Hua Chen
    • Ming Zhao
    • Juan Liang
  • View Affiliations

  • Published online on: April 23, 2012     https://doi.org/10.3892/ijmm.2012.980
  • Pages: 93-99
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Abstract

The fruit of Brucea javanica L. is a common herb used in Chinese medicine for the treatment of a variety of cancers. Our research group has previously identified bruceine D (BD), a quassinoid found abundantly in B. javanica, to have potent cytotoxic effect on a number of pancreatic cancer cell lines, including Panc-1, SW1990 and Capan-1 cells. In the present study, we showed that BD was also able to inhibit the growth of the Capan-2 human pancreatic adenocarcinoma cell line, but it exerted only modest cytotoxicity on the WRL68 human hepatocyte cell line and a human pancreatic progenitor cell line. The antiproliferative effects of BD were comparable to those exhibited by camptothecin and gemcitabine in our culture system. We found a dose-dependent decrease of the mitochondrial membrane potential in BD-treated Capan-2 cells as measured by the JC-1 assay. BD exposure was able to attenuate the expression of Bcl-2 protein in Capan-2 cells as detected by western blot analysis. In addition, the expression of both caspase 9 and caspase 3 in BD-treated Capan-2 cells was significantly accentuated. Moreover, BD was capable of inducing the fragmentation of genomic DNA in Capan-2 cells as evidenced by Hoechst staining. Cell cycle analysis demonstrated that BD could increase the percentage of Capan-2 cells in the subG1 phase in a dose-related manner. An increase in the apoptosis of Capan-2 cells was also observed by Annexin V and PI staining. These results unequivocally indicate that BD induces cytotoxicity in Capan-2 cells via the induction of cellular apoptosis involving the mitochondrial pathway.

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July 2012
Volume 30 Issue 1

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

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Spandidos Publications style
Liu L, Lin Z, Leung P, Chen L, Zhao M and Liang J: Involvement of the mitochondrial pathway in bruceine D-induced apoptosis in Capan-2 human pancreatic adenocarcinoma cells. Int J Mol Med 30: 93-99, 2012
APA
Liu, L., Lin, Z., Leung, P., Chen, L., Zhao, M., & Liang, J. (2012). Involvement of the mitochondrial pathway in bruceine D-induced apoptosis in Capan-2 human pancreatic adenocarcinoma cells. International Journal of Molecular Medicine, 30, 93-99. https://doi.org/10.3892/ijmm.2012.980
MLA
Liu, L., Lin, Z., Leung, P., Chen, L., Zhao, M., Liang, J."Involvement of the mitochondrial pathway in bruceine D-induced apoptosis in Capan-2 human pancreatic adenocarcinoma cells". International Journal of Molecular Medicine 30.1 (2012): 93-99.
Chicago
Liu, L., Lin, Z., Leung, P., Chen, L., Zhao, M., Liang, J."Involvement of the mitochondrial pathway in bruceine D-induced apoptosis in Capan-2 human pancreatic adenocarcinoma cells". International Journal of Molecular Medicine 30, no. 1 (2012): 93-99. https://doi.org/10.3892/ijmm.2012.980