Objective: To evaluate the effects of n-hexane insoluble fraction (HIF) of Ficus septica leaves in combination with doxorubicin on cytotoxicity, cell cycle and apoptosis induction of breast cancer T47D cell lines. Methods: The in vitro drugs-stimulated cytotoxic effects were determined using MTT assay. Analysis of cell cycle distribution was performed using flowcytometer and the data was analyzed using ModFit LT 3.0 program. Apoptosis assay was carried out by double staining method using ethydium bromide-acridin orange. The expression of cleaved-poly (ADP-ribose) polymerase (PARP) on T47D cell lines was identified using immunocytochemistry. Results:The combination exhibited higher inhibitory effect on cell growth than the single treatment of doxorubicin in T47D cells. In addition, combination of doxorubicin and HIF increased the incidence of cells undergoing apoptosis. HIF could improve doxorubicin cytotoxic effect by changing the accumulation of cell cycle phase from G2/M to G1 phase. The combination also exhibited upregulation of cleaved-PARP in T47D cells. Conclusions: Based on this results, HIF is potential to be developed as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.

Objective: To investigate the estrogenic effect of (8,9)-furanyl-pterocarpan-3-ol (FPC) on growth of human breast cancer T47D cells and the interactions between the FPC and tamoxifen (TAM), on the growth of estrogen receptor-dependent breast cancer T47D cells.Methods:T47D cells were treated with FPC alone (0.01-200 μmol/L) or in combination with TAM 20 nmol/L. The proliferation effect of FPC were conducted on T47D cells in vitro by MTT test. Furthermore, the expression of ERα or c-Myc were also determined by immunohistochemistry.Results:inhibitory effect on T47D cells, wheraes co-administered with low concentration (less than 1μmol/L) of FPC attenuated to promote cell proliferation. In contrast, the combination of TAM with higher doses (more than 20 μmol/L) of FPC showed growth inhibitory. This result was supported by immunocytochemistry studies that the administration of 20 nmol/L TAM down-regulated ER-αand c-Myc, but the combination of 20 nmol/L TAM and 1 μmol/L FPC robustly up-regulated expression of ER-α. Thus, the reduced growth inhibition of TAM 20 nmol/L by FPC 1 μmol/L on T47D cells may act via the modulation of ER-α.Conclusions:The findings indicate and suggest that FPC had estrogenic activity at low The results indicated that administration of an anti-estrogen TAM showed growth concentrations and anti-estrogenic effect that are likely to be regulated by c-Myc and estrogen receptors. We also confirm that low concentration of FPC attenuated the growth-inhibitory effects of TAM on mammary tumor prevention. Therefore, the present study suggests that caution is warranted regarding the consumption of dietary FPC by breast cancer patients while on TMA therapy.

Objective:To evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells (MCF-7/Dox) in cytotoxicity apoptosis and P-glycoprotein (Pgp) expression in combination with doxorubicin.
Methods:The cytotoxic properties, 50%inhibition concentration (IC50) and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin (MCF-7/Dox) cells were determined using MTT assay. Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange. Immunocytochemistry assay was performed to determine the level and localization of Pgp.
Results: Single treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC50 value of 11 μmol/L. Thus, combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect (CI>1.0). Hesperidin did not increase the apoptotic induction, but decreased the Pgp expressions level when combined with doxorubicin in low concentration.
Conclusions: Hesperidin has cytotoxic effect on MCF-7/Dox cells with IC50 of 11 μmol/L. Hesperidin did not increased the apoptotic induction combined with doxorubicin. Co-chemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.

OBJECTIVETo evaluate the effects of n-hexane insoluble fraction (HIF) of Ficus septica leaves in combination with doxorubicin on cytotoxicity, cell cycle and apoptosis induction of breast cancer T47D cell lines.

METHODSThe in vitro drugs-stimulated cytotoxic effects were determined using MTT assay. Analysis of cell cycle distribution was performed using flowcytometer and the data was analyzed using ModFit LT 3.0 program. Apoptosis assay was carried out by double staining method using ethydium bromide-acridin orange. The expression of cleaved-poly (ADP-ribose) polymerase (PARP) on T47D cell lines was identified using immunocytochemistry.

RESULTSThe combination exhibited higher inhibitory effect on cell growth than the single treatment of doxorubicin in T47D cells. In addition, combination of doxorubicin and HIF increased the incidence of cells undergoing apoptosis. HIF could improve doxorubicin cytotoxic effect by changing the accumulation of cell cycle phase from G2/M to G1 phase. The combination also exhibited upregulation of cleaved-PARP in T47D cells.

CONCLUSIONSBased on this results, HIF is potential to be developed as co-chemotherapeutic agent for breast cancer by inducing apoptosis and cell cycle arrest. However, the molecular mechanism need to be explored further.

Antineoplastic Agents ; chemistry ; pharmacology ; Apoptosis ; drug effects ; Breast Neoplasms ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Doxorubicin ; pharmacology ; Female ; Ficus ; chemistry ; Flow Cytometry ; Hexanes ; chemistry ; pharmacology ; Humans ; Immunohistochemistry ; Solubility

Objective:To determine the effect of rice bran extract (RBE) in combination with doxorubicin on 4T1 triple-negative breast cancer cells and NIH-3T3 cells. Methods:RBE was obtained by maceration with n-hexane. The phytochemical profile of RBE was observed using high-performance liquid chromatography. Cytotoxic effect of RBE was evaluated through MTT assay. In addition, flow cytometry was used for cell cycle and apoptosis analysis. Cellular senescence was observed using SA-β-Gal assay and intracellular reactive oxygen species (ROS) levels were evaluated using DCFDA staining. The pro-oxidant property of RBE was also evaluated through 1-chloro-2,4-dinitrobenzene spectrophotometry and molecular docking. Results:RBE was obtained with a yield of 18.42％ w/w and contained tocotrienols as the major compound. RBE exerted no cytotoxic effect on 4T1 and NIH-3T3 cells. However, RBE in combination with doxorubicin decreased 4T1 cell viability synergistically (combination index<0.9) and induced apoptosis and senescence on 4T1 cells. RBE significantly decreased senescence in doxorubicin-treated NIH-3T3 cells. Additionally, RBE did not increase ROS levels in doxorubicin-treated 4T1 cells. Meanwhile, the combination of RBE and doxorubicin reduced ROS levels in NIH-3T3 cells. RBE significantly reduced glutathione-S-transferase activity and alpha-tocotrienol interacted with glutathione-S-transferase in the glutathione binding site. Conclusions:Rice bran may be used as a co-chemotherapeutic agent to improve the therapeutic effectiveness of doxorubicin while protecting against the cellular senescence effects of doxorubicin on healthy cells.

OBJECTIVETo evaluate of hesperidin to overcome resistance of doxorubicin in MCF-7 resistant doxorubicin cells (MCF-7/Dox) in cytotoxicity apoptosis and P-glycoprotein (Pgp) expression in combination with doxorubicin.

METHODSThe cytotoxic properties, 50% inhibition concentration (IC50) and its combination with doxorubicin in MCF-7 cell lines resistant to doxorubicin (MCF-7/Dox) cells were determined using MTT assay. Apoptosis induction was examined by double staining assay using ethidium bromide-acridine orange. Immunocytochemistry assay was performed to determine the level and localization of Pgp.

RESULTSSingle treatment of hesperidin showed cytotoxic activity on MCF-7/Dox cells with IC50 value of 11 µmol/L. Thus, combination treatment from hesperidin and doxorubicin showed addictive and antagonist effect (CI>1.0). Hesperidin did not increase the apoptotic induction, but decreased the Pgp expressions level when combined with doxorubicin in low concentration.

CONCLUSIONSHesperidin has cytotoxic effect on MCF-7/Dox cells with IC50 of 11 µmol/L. Hesperidin did not increased the apoptotic induction combined with doxorubicin. Co-chemotherapy application of doxorubicin and hesperidin on MCF-7/Dox cells showed synergism effect through inhibition of Pgp expression.