Molecular mechanism of ursolic acid induced apoptosis in poorly differentiated endometrial cancer HEC108 cells

  • Authors:
    • Yumiko Achiwa
    • Kiyoshi Hasegawa
    • Yasuhiro Udagawa
  • View Affiliations

  • Published online on: August 1, 2005     https://doi.org/10.3892/or.14.2.507
  • Pages: 507-512
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Abstract

We studied the effect of ursolic acid, a pentacyclic triterpene acid, on the growth of poorly differentiated type endometrial cancer HEC108 cells in vitro. Ursolic acid strongly inhibited the growth of HEC108 cells in a dose- and time-dependent manner. Morphological changes characteristic of apoptosis were observed in ursolic acid-treated cells, such as the presence of apoptotic bodies and fragmentation of DNA to oligonucleosomal-sized fragments. Investigation of caspase activity in ursolic acid-treated HEC108 cells showed that exposure at 50, 75 or 100 µM induced marked increases in caspase-3 activity (after 24 h) to 5.00, 11.76 or 12.75 times that of control levels, while cleaved caspase-3 levels increased in dose-dependent manner after 24 h. Activation of caspase was shown to lead to the cleavage of target proteins such as PARP. Ursolic acid treatment also resulted in a cleavage of poly(ADP-ribose) polymerase in a dose-dependent manner. Testing whether caspase-3 activation and DNA polymerase activity were inhibited by the addition of Ac-DEDV-HOC during ursolic acid treatment showed that 50 µM Ac-DEDV-HOC inhibited caspase-3 activity in treated cells. A mitochondrial pathway has been suggested to be involved in ursolic acid-induced apoptosis because the treatment induces mitochondria cytochrome c release. Experimentally, we found that anti-apoptotic Bcl-2 protein levels decreased after ursolic acid treatment, while Bax expression increased. Our results indicated that ursolic acid induced apoptotic processes in these poorly differentiated endometrial cancer cells occurs through mechanisms involving mitochondrial pathways and Bcl-2 family proteins.

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August 2005
Volume 14 Issue 2

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

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Spandidos Publications style
Achiwa Y, Hasegawa K and Udagawa Y: Molecular mechanism of ursolic acid induced apoptosis in poorly differentiated endometrial cancer HEC108 cells. Oncol Rep 14: 507-512, 2005.
APA
Achiwa, Y., Hasegawa, K., & Udagawa, Y. (2005). Molecular mechanism of ursolic acid induced apoptosis in poorly differentiated endometrial cancer HEC108 cells. Oncology Reports, 14, 507-512. https://doi.org/10.3892/or.14.2.507
MLA
Achiwa, Y., Hasegawa, K., Udagawa, Y."Molecular mechanism of ursolic acid induced apoptosis in poorly differentiated endometrial cancer HEC108 cells". Oncology Reports 14.2 (2005): 507-512.
Chicago
Achiwa, Y., Hasegawa, K., Udagawa, Y."Molecular mechanism of ursolic acid induced apoptosis in poorly differentiated endometrial cancer HEC108 cells". Oncology Reports 14, no. 2 (2005): 507-512. https://doi.org/10.3892/or.14.2.507