Astragalus saponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells

  • Authors:
    • Kathy Ka-Wai Auyeung
    • Nga-Lai Mok
    • Ching-Man Wong
    • Chi-Hin Cho
    • Joshua Ka-Shun Ko
  • View Affiliations

  • Published online on: September 1, 2010     https://doi.org/10.3892/ijmm_00000471
  • Pages: 341-349
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Abstract

We have previously demonstrated that the total saponins of Astragalus membranaceus (AST) possess potential anti-tumorigenic effects in human colon cancer cells and tumor xenografts. In the present study, the proapoptotic effects of AST were investigated in native and cytokine-induced HT-29 cells to further unveil its mechanism of action. Growth-inhibitory action of AST (60 µg/ml) was demonstrated in native HT-29 cells, which was exaggerated in tumor necrosis factor (TNF) (5 ng/ml)-induced cells. These were accompanied by caspase 3 activation, cleavage of poly(ADP-ribose) polymerase and a subsequent increase in apoptotic cell numbers. Furthermore, activation of procaspase 8 indicates that the extrinsic apoptotic pathway was involved, while cleavage of Bid into t-Bid implicates cross-talk with the intrinsic apoptotic pathway. Alternatively, AST caused S and G2/M phase arrest, while in cytokine-induced cells S phase arrest was predominant. Further adding to our recent suggestion on its correlation with phosphatidylinositol 3-kinase (PI3K)-Akt signaling, we have now revealed that AST caused overexpression of PTEN and down-regulation of mammalian target of rapamycin (mTOR) expression. Nevertheless, these events were preceded by a decrease in nuclear factor-κB (NF-κB)/DNA binding activity with continuous ERK 1/2 activation. Some of these effects became more intense in cytokine-induced cells. Our findings in this study suggest that AST induces the extrinsic apoptotic cascade and causes cell cycle arrest in HT-29 cells by modulation of both mTOR and ERK signaling pathways, of which inhibition of NF-κB is important in the latter mechanism. Most of the above processes are more pronounced in cytokine-induced cells.

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September 2010
Volume 26 Issue 3

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

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APA
Auyeung, K.K., Mok, N., Wong, C., Cho, C., & Ko, J.K. (2010). Astragalus saponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells . International Journal of Molecular Medicine, 26, 341-349. https://doi.org/10.3892/ijmm_00000471
MLA
Auyeung, K. K., Mok, N., Wong, C., Cho, C., Ko, J. K."Astragalus saponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells ". International Journal of Molecular Medicine 26.3 (2010): 341-349.
Chicago
Auyeung, K. K., Mok, N., Wong, C., Cho, C., Ko, J. K."Astragalus saponins modulate mTOR and ERK signaling to promote apoptosis through the extrinsic pathway in HT-29 colon cancer cells ". International Journal of Molecular Medicine 26, no. 3 (2010): 341-349. https://doi.org/10.3892/ijmm_00000471