ABSTRACT
Long-term use of doxorubicin (DOX) causes several side effects, especially induction of metastasis, in breast cancercells. Pentagamaboronon-0 (PGB-0) or 2,5-bis(4-boronic acid benzylidene) cyclopentanone is a novel curcumin analogthat exerts cytotoxic effects on Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer cells. Theobjective of this study was to evaluate PGB-0 as a co-chemotherapeutic agent on DOX-induced metastatic breastcancer cells, 4T1. Potential cytotoxic and antimetastatic activities of PGB-0 were screened by molecular docking underPLANTS software, which revealed that the PGB-0 interacted with matrix metalloproteinase-9 (MMP-9) and InhibitorKappa β Kinase (IKKβ). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay showed that PGB-0 andDOX exhibited cytotoxic effects on 4T1 breast cancer cells, with IC50 values of 294 and 2.4 µM, respectively, andsynergistically increased the cytotoxicity of DOX. Results of propidium iodide staining flow cytometry revealed thatthe PGB-0 and its combination with DOX induced cell cycle arrest in the S phase and the G2/M phase, respectively.In addition, PGB-0 and its combination with DOX induced apoptosis. Regarding the antimetastatic activity, a singletreatment with PGB-0 inhibited cell migration, while its combination with DOX inhibited cell migration with morepotency than that with single treatment, as assessed through wound healing assay. Gelatin zymography revealed thatthe PGB-0 and its combination with DOX inhibited MMP-9 activity. Immunoblotting assay showed that the PGB-0and its combination with DOX decreased the expression of Rac1 and p120. In conclusion, PGB-0 increased thecytotoxicity and inhibited the induction of metastasis by DOX in breast cancer cells.
ABSTRACT
Cisplatin is drug of choice toward cervical cancer despite having many side effects, thus researches are conducted in order to find the effective and synergistic co-chemoterapeutic agent combined with cisplatin. In this study, we observed the potential of the cinnamon essential oil (CEO) isolated from Cinnamomum burmannii as cochemoterapeutic agent of cisplatin on HeLa cells covering cytotoxic effect, cell cycle modulation and induction of apoptosis. Cytotoxic effect was determined by using MTT assay; while induction of apoptosis and cell cycle profile were observed by using flow cytometry. At 24 hours of incubation, CEO showed cytotoxic effect on HeLa cells with IC50 value of 250 μg/mL, while cisplatin showed cytotoxic effect with IC50 value of 18 μM. Combination of CEO and cisplatin reduced cells viability compared to cisplatin solely. Moreover, flow cytometry using annexin-V and PI showed that CEO and its combination with cisplatin induced apoptosis lower than cisplatin alone at 24 hours of incubation. Further analysis on the cell cycle progression showed that CEO induced S-phase arrest on HeLa cells, cisplatin induced G1 arrest, while combination of CEO and cisplatin induced G2/M arrest. Thus, the inhibition of HeLa cells growth at 24 hours is likely through cell cycle modulation rather than apoptosis.