Open Access

Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells

  • Authors:
    • Yongqing Liu
    • Chunwen Yue
    • Juan Li
    • Jing Wu
    • Shikang Wang
    • Deqing Sun
    • Yanxia Guo
    • Zhaomin Lin
    • Denglu Zhang
    • Rongmei Wang
  • View Affiliations

  • Published online on: December 20, 2017     https://doi.org/10.3892/ol.2017.7664
  • Pages: 2871-2880
  • Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Retigeric acid B (RAB), a natural compound isolated from lichen, has been demonstrated to inhibit cell growth and promote apoptosis in prostate cancer (PCa) cells. The present study evaluated the function of RAB combined with clinical chemotherapeutic drugs in PCa cell lines by MTT assay, reverse transcription quantitative polymerase chain reaction and western blot analysis, and identified that RAB at low doses produced significant synergistic cytotoxicity in combination with cisplatin (CDDP); however, no marked synergism between RAB and the other chemotherapeutics was observed. Additional studies revealed that RAB exerted an inhibitory effect on DNA damage repair pathways, including the nucleotide excision repair and mismatch repair pathways, which are involved in the sensitivity to CDDP‑based chemotherapy, as suggested by the significantly downregulated expression of certain associated repair proteins. Notably, Excision repair cross‑complementing 1, a critical gene in the nucleotide excision repair pathway, exhibited the most significant decrease. When combined with CDDP, RAB‑mediated impairment of DNA repair resulted in prolonged DNA damage, as demonstrated by the long‑lasting appearance of phosphorylation of histone H2AX at Ser139, which potentially enhanced the chemosensitivity to CDDP. Concurrently, the proapoptotic protein death receptor 5 (DR5) was activated by RAB, which also enhanced the chemotherapeutic response of CDDP. Knockdown of DR5 partially blocked RAB‑CDDP synergism, suggesting the crucial involvement of DR5 in this event. The results of the present study identified that RAB functioned synergistically with CDDP to increase the efficacy of CDDP by inhibiting DNA damage repair and activating DR5, suggesting the mechanistic basis for the antitumor effect of RAB in combination with current chemotherapeutics.
View Figures
View References

Related Articles

Journal Cover

March-2018
Volume 15 Issue 3

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Yue C, Li J, Wu J, Wang S, Sun D, Guo Y, Lin Z, Zhang D, Wang R, Wang R, et al: Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells. Oncol Lett 15: 2871-2880, 2018
APA
Liu, Y., Yue, C., Li, J., Wu, J., Wang, S., Sun, D. ... Wang, R. (2018). Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells. Oncology Letters, 15, 2871-2880. https://doi.org/10.3892/ol.2017.7664
MLA
Liu, Y., Yue, C., Li, J., Wu, J., Wang, S., Sun, D., Guo, Y., Lin, Z., Zhang, D., Wang, R."Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells". Oncology Letters 15.3 (2018): 2871-2880.
Chicago
Liu, Y., Yue, C., Li, J., Wu, J., Wang, S., Sun, D., Guo, Y., Lin, Z., Zhang, D., Wang, R."Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells". Oncology Letters 15, no. 3 (2018): 2871-2880. https://doi.org/10.3892/ol.2017.7664