Synergistic effects of ethyl acetate fraction of Ficus septica Burm. f. and doxorubicin chemotherapy on T47D human breast cancer cell line.
OBJECTIVE
Previously, ethanolic extract of Ficus septica Burm. f. (Moraceae) leaves and its ethyl acetate soluble fraction (EASF) exhibited potent cytotoxic effects on T47D breast cancer cells. In the present study, we further investigated the effects of EASF of ethanolic extract of F. septica leaves in combination with doxorubicin on T47D breast cancer cell line in cytotoxicity, cell cycle arrest and apoptosis induction.


METHODS
The cytotoxic effect analysis on T47D cells was carried out using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Analysis of cell cycle distribution was performed using a flowcytometer and the data were analyzed using ModFit LT 3.0 program. Apoptosis assay was carried out by double staining method using ethidium bromide-acridin orange. The expression of cleaved-poly ADP-ribose polymerase in the T47D cell line was identified using immunohistochemical techniques.


RESULTS
The combination of doxorubicin (2 to 8 nmol/L) with EASF (0.875 to 7 μg/mL) more potently inhibited cell growth than the single treatment of doxorubicin in T47D cells. In addition, the combination of doxorubicin and EASF could increase the incidence of cells undergoing apoptosis. EASF was found to improve cytotoxic effect of doxorubicin by changing the inhibition of cell cycle G(2)/M to G(1) phase. The combination also exhibited a more intensive stimulatory effect on cleaved-PARP expression in T47D cells than the single treatment.


CONCLUSIONS
It is concluded that EASF may enhance doxorubicin activities in T47D cells by inducing apoptosis and cell cycle arrest.
Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Jogjakarta 55281, Indonesia. agungendronugroho@yahoo.com
Agung E
AE
Nugroho
Adam
A
Hermawan
P
P
Putri D
Edy
E
Meiyanto
Lukman
L
Hakim
D000085:Acetates; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D005260:Female; D030681:Ficus / Q000737:chemistry*; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use
D000085:Acetates; D010936:Plant Extracts; C007650:ethyl acetate; D004317:Doxorubicin