ABSTRACT
Boron containing compound (BCC) offers the potential further development for therapy against malignant cancers.We successfully synthesized a new compound based on curcumin structure (curcumin analogue) containing boronatoms, namely, CCB-2 and revealed its cytotoxic activities on various cancer cell lines. The compound was simplysynthesized based on aldol condensation using acetone and 4-formylphenyl boronic acid resulted a symmetry CCB-2.The compound was then tested for cytotoxic activities in several cell lines. CCB-2 demonstrated cytotoxic effect onMCF-7/HER-2, MCF-7, RAW 264.7, and 4T1 with IC50 value of 12 µM, 54 µM, 26 µM, and < 10 µM, respectively,while less toxic in fibroblast cells. This compound performed superior cytotoxic against highly metastatic cancer cell,4T1. In addition, CCB-2 induced cells accumulation in G2/M phase, but decreased the accumulation of intracellularReactive oxygen species level in 4T1 cells. All the data suggest that this new compound is promising to be developedas anti-cancer agent rather than for Boron Neutron Capture Therapy-based cancer therapy
ABSTRACT
New approach of breast cancer therapy is developed toward combination therapy with agent that have a specific molecular target. Our previous study showed that Citrus aurantifolia lime peels ethanolic extract [CPE] increased the sensitivity of MCF-7 cells againts doxorubicin. This study aims to observe the mechanism of combination CPE and doxorubicin in cell cycle modulation and apoptosis on MCF-7 cells. The assays were performed in the study were cell cycle assay, apoptosis induction, and immunocytochemistry of MCF-7 cells. The effect on the modulation of cell cycle and apoptosis were observed by flowcytometry assay in both single dose of CPE and its combination with Doxorubicin. Cell cycle distribution were observed with flowcytometer FACS-Calibur and its data was analyzed by Cell Quest program. Apoptotic induction in MCF-7 cells was examined using acrydine orange-ethidium bromide [AO-EtBr] double staining. Immunocytochemistry assay was done to observe the expression of apoptotic regulation protein p53 and Bcl-2. The result showed that CPE 6 microg/mL induced apoptosis and cell accumulation at G1 phase, while CPE 15 microg/mL induced apoptosis and cell accumulation at G2/M phase. The combination of doxorubicin 200 nM with CPE 6 microg/mL increased apoptosis induction than their single treatment, and cell accumulation at G2/M phase. Evidence of apoptosis and protein expression of p53 and Bcl-2 indicated that both single applications and combinations of CPE and doxorubicin is able to increase apoptotic bodies of MCF-7 cells by increasing the proteins expression. This results suggested that CPE could perform as co-chemotherapeutic agent with doxorubicin on breast cancer cells
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>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.</p>