Death receptor-dependent and -independent pathways in anticancer drug-induced apoptosis of breast cancer cells

  • Authors:
    • Ryungsa Kim
    • Kazuaki Tanabe
    • Manabu Emi
    • Yoko Uchida
    • Tetsuya Toge
  • View Affiliations

  • Published online on: November 1, 2003     https://doi.org/10.3892/or.10.6.1925
  • Pages: 1925-1930
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Abstract

Apoptosis is a crucial event for anticancer drug efficacy. The signal pathways activated by anticancer drugs are classified as death receptor (DR) -dependent or -independent. The mechanisms by which anticancer drugs induce apoptosis via DR-dependent pathways are not fully understood. In the present study, we assessed differential activation of signal transduction pathways leading to apoptosis by anticancer drugs in breast cancer cell lines. Three breast cancer cell lines, MDA-MB-231, MCF-7, and MCF-7ADM, which is drug-resistant, were used. Drug sensitivity and apoptosis were assessed by MTT assay and TUNEL, respectively. Expression of apoptosis-related protein was assessed by Western blotting and RT-PCR. The sensitivities of MDA-MB-231 and MCF-7 cells to mitomycin C (MMC) and adriamycin (ADM) were similar. In contrast, sensitivity of MDA-MB-231 cells to paclitaxel (TXL) was 30-fold greater than that of MCF-7 cells, 0.03 µM in MDA-MB-231 and 0.9 µM in MCF-7 cells, respectively. Treatment with MMC increased expression of DR4 and Fas in a time-dependent manner in MDA-MB-231 cells. Treatment with ADM increased expression of DR4 and DR5 but not Fas, whereas treatment with TXL increased expression of Fas but not DR4 and DR5 in MDA-MB-231 cells. Although treatment of MCF-7 cells with ADM increased expression of DR4 and DR5 but not Fas, expression of DR4, DR5, and Fas by the drug-resistant cells did not change following treatment with ADM. Activation of Fas, DR4, and DR5 in drug-sensitive cells in response to anticancer drugs is dependent on the cytotoxic effect of each drug. In drug-resistant cells, apoptosis is induced via DR-independent pathways mediated by mitochondrial dysfunction.

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November-December 2003
Volume 10 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim R, Tanabe K, Emi M, Uchida Y and Toge T: Death receptor-dependent and -independent pathways in anticancer drug-induced apoptosis of breast cancer cells. Oncol Rep 10: 1925-1930, 2003
APA
Kim, R., Tanabe, K., Emi, M., Uchida, Y., & Toge, T. (2003). Death receptor-dependent and -independent pathways in anticancer drug-induced apoptosis of breast cancer cells. Oncology Reports, 10, 1925-1930. https://doi.org/10.3892/or.10.6.1925
MLA
Kim, R., Tanabe, K., Emi, M., Uchida, Y., Toge, T."Death receptor-dependent and -independent pathways in anticancer drug-induced apoptosis of breast cancer cells". Oncology Reports 10.6 (2003): 1925-1930.
Chicago
Kim, R., Tanabe, K., Emi, M., Uchida, Y., Toge, T."Death receptor-dependent and -independent pathways in anticancer drug-induced apoptosis of breast cancer cells". Oncology Reports 10, no. 6 (2003): 1925-1930. https://doi.org/10.3892/or.10.6.1925