Ursolic Acid Enhances Doxorubicin Cytotoxicity on MCF-7 Cells Mediated by G2/M Arrest

ISCC (Indonesian Journal of Cancer Chemoprevention)

ARTICLE

Ibrahim Arifin¹  Adam Hermawan²  Muthi' Ikawati²  Sari Haryanti¹  Anindyajati Anindyajati³  Edy Meiyanto² 

[1] Faculty of Pharmacy, Universitas Wahid Hasyim;Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Jalan Sekip Utara;Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada

关键词: ursolic acid;    doxorubicin;    co-chemotherapeutic agent;    breast cancer;    cell cycle;   

DOI  :  10.14499/indonesianjcanchemoprev3iss3pp410-418

学科分类：药学

来源: Indonesian Society for Cancer Chemoprevention

【 摘 要 】

Ursolic acid has been widely known to possess biological activity against numerous tumor cell lines. Previous studies revealed its cytotoxicity on several cancer cells in vitro by either inducing apoptosis or cell cycle modulation. This study was conducted to investigate ursolic acid’s cytotoxicity solely and in combination with a chemotherapeutic agent, doxorubicin, on MCF-7 breast cancer cells, followed by observation on its mechanism. Cytotoxicity of single and combinational treatment of ursolic acid and doxorubicin on MCF-7 breast cancer cells were conducted by using MTT assay. Single treatment was then evaluated by determining IC 50 value, while combinational treatment was evaluated by analyzing cell viability and evaluating combination index (CI). To explore the mechanism underlying cytotoxic effect on respected cells, further analysis on cell cycle profile of single and combinational treatment was conducted by flow cytometry. Twenty four hours treatment of ursolic acid inhibited MCF-7 cells’ growth with IC 50 value of 37 µM, while combinational treatment showed that several concentration combinations of ursolic acid and doxorubicin exhibited synergism of cytotoxic activity on MCF-7 cells, giving optimum CI value of 0.54. Flow cytometric analysis showed that combinational treatment induced G2/M arrest in MCF-7 cells. These results show that ursolic acid is promising to be developed as either single chemopreventive agent, or as doxorubicin’s co-chemotherapeutic agent in breast cancer treatment. Observation on the selectivity as part of safety aspect together with in silico , in vitro , and in vivo study on its molecular mechanism should be conducted.

【 授权许可】

CC BY-NC