Indonesian Journal of Cancer Chemoprevention
Vol 3, No 3 (2012)

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


Arifin, Ibrahim ( Faculty of Pharmacy, Universitas Wahid Hasyim, Semarang ) , Hermawan, Adam ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada ) , Ikawati, Muthi ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada ) , Haryanti, Sari ( Balai Besar Penelitian dan Pengembangan Tanaman Obat dan Obat Tradisional, Tawangmangu ) , Anindyajati, . ( Cancer Chemoprevention Research Center Faculty of Pharmacy, Universitas Gadjah Mada ) , Meiyanto, Edy ( Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada )



Article Info

Publish Date
19 Apr 2014

Abstract

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  IC50  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  IC50  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.Keywords: ursolic acid, doxorubicin,co-chemotherapeutic agent, breast cancer, cell cycle


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