Combination of Cisplatin and Cinnamon Essential Oil Inhibits HeLa Cells Proliferation through Cell Cycle Arrest.

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.

Cytotoxic activity and apoptosis induction of 8-hydroxyisocapnolactone-2´,3´-diol and its combination with Doxorubicin on MCF-7 and T47D cells.

The cytotoxic activity and apoptosis induction of 8-hydroxyisocapnolactone-2΄,3΄-diol (HICD) and its combination with doxorubicin (Doxo) on MCF-7 and T47D cells have been evaluated. The cytotoxic assay was performed using MTT method. The IC50 was used to express the cytotoxic potency, while the combination index (CI) was calculated to determine the effect of combination. The apoptotic assay was carried out using acrydine orange - ethidium bromide double staining method, while Bcl-2 and Bax expression were investigated by immunocytochemistry. The HICD exhibited cytotoxic activity on MCF-7 and T47D cells with the IC50 of 8 μg/ml (21.2 μM) and 4 μg/ml (10.6 μM), respectively. The combination of HICD with Doxo showed synergistic effect and increased apoptosis induction on both cell lines. The HICD did not affect Bcl-2 but increased Bax expression on MCF-7 cells, while on T47D cells it suppressed Bcl-2 expression but did not modulate Bax expression.