Differential effects of RhoA signaling on anticancer agent-induced cell death

  • Authors:
    • Won Ki Kang
    • Inkyoung Lee
    • Ukyoung Ko
    • Chaehwa Park
  • View Affiliations

  • Published online on: February 1, 2005     https://doi.org/10.3892/or.13.2.299
  • Pages: 299-304
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Substantial evidence exists to support a role for RhoA signaling in adhesion and cytoskeletal reorganization, while relatively less is known about the participation of RhoA on cell survival. We provide evidence that RhoA functions as a differential modulator of apoptosis induced by anticancer agents. Specifically, both RhoA and caRhoA induce statistically significant resistance to statin, etoposide, 5-FU and taxol while increasing sensitivity to vincristine (all p<0.001). The IC50 values for statin, etoposide, 5-fluorouracil (5-FU) and taxol in caRhoA transfectant were 8.70±0.74, 4.08±0.12, 4.12±0.12 µg/ml and 3.84±0.16 ng/ml, respectively, whereas the respective IC50 values in the mock-transfected control were 3.40±0.21, 1.12±0.06, 1.21±0.06 µg/ml and 2.84±0.15 ng/ml. This represented a 2.6-, 3.5-, 3.2- and 1.4-fold resistance to statin, etoposide, 5-FU and taxol, respectively. In contrast, caRhoA increased sensitivity to vincristine, decreasing IC50 values from 4.61±0.46 to 3.73±0.44 ng/ml (p<0.001). Western blot analysis demonstrated that RhoA mediates induction of E2F-1, Cdk2 and PCNA, accompanying concurrent reduction in p21 and p27. However, cleavage assays of poly (ADP-ribose) polymerase, BID, caspase-8 and caspase-3 indicate that the cell growth modulation mediated by RhoA in response to these anticancer agents occurs through the inhibition of apoptosis. Taken together, these results indicate that RhoA differentially modulates cancer cell death depending on the anticancer agent.

Related Articles

Journal Cover

February 2005
Volume 13 Issue 2

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Kang WK, Lee I, Ko U and Park C: Differential effects of RhoA signaling on anticancer agent-induced cell death. Oncol Rep 13: 299-304, 2005.
APA
Kang, W.K., Lee, I., Ko, U., & Park, C. (2005). Differential effects of RhoA signaling on anticancer agent-induced cell death. Oncology Reports, 13, 299-304. https://doi.org/10.3892/or.13.2.299
MLA
Kang, W. K., Lee, I., Ko, U., Park, C."Differential effects of RhoA signaling on anticancer agent-induced cell death". Oncology Reports 13.2 (2005): 299-304.
Chicago
Kang, W. K., Lee, I., Ko, U., Park, C."Differential effects of RhoA signaling on anticancer agent-induced cell death". Oncology Reports 13, no. 2 (2005): 299-304. https://doi.org/10.3892/or.13.2.299