Combining drugs with different mechanism of action in nanocarriers is becoming a promising strategy in cancer therapy. In the present study, the anticancer activity of the combination of doxorubicin (DOX) and pravastatin (PRV) loaded in nanoemulsions (NEs) was evaluated in HCT 116 colon cancer cells. The NE formulas (NEa and NEb) consisted of different weight fractions of the surfactant mixture of Eumulgin HRE 40/ Soya phosphatidylcholine/ sodium oleate at a fixed weight ratio of 3.5:3.0:3.5, cholesterol (CHO), Tris- HCl buffer (pH 7.22), and 1-octanol. The cytotoxicity of the drug formulas, loaded in either water or NEs, was assessed through 3-(4, 5 Dimethylthiazole- 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay, while the mechanism of cell death was determined by observing the morphological changes of treated cells under light microscope and identifying apoptosis by using the ApopNexin FITC kit and DAPI nuclear staining. It has been found that reducing the concentration of DOX from 15 to 7.5µM by formulating it with 7.5µM of PRV in NEa (NEa (1 DOX:1 PRV)) has preserved its cytotoxicity against HCT-116 cancer cells. The present study proved that the combination of the PRV and DOX loaded in NEa formulations improved the therapeutic potential of both of PRV and DOX as anticancer drugs.

One of the compounds found efficacious as an anti-proliferative on colon cancer is alpha-mangosteen, a xanthon compound that is abundant in pericarp of mangosteen. This study focused to evaluate anticancer activity of the ethanolic extract of pericarp of mangosteen (Garcinia mangostana Linn.) on WiDr colon cancer cells and to observe the affinity of alpha-mangosteen in inhibiting IKK and VEGF. Cytotoxic effect was tested by MTT assay and apoptosis induction was evaluated by double staining method on WiDr colon cancer cells, while interaction between alpha-mangosteen to the receptors was measured by molecular docking. The ethanolic extract was proven to have cytotoxic activity against WiDr colon cancer cells with IC50 of 25 µg/mL. In addition, the observation of apoptosis induction by double-staining method showed that apoptosis associated the cytotoxic effect of ethanolic extract of pericarp of mangosteen (EPM) on WiDr colon cancer cells. Molecular docking showed that active compounds in pericarp of mangosteen could compete with the native ligand of VEGF because the docking score of alpha-mangosteen was almost equal with native ligand. From these results we could be concluded that the cytotoxic effect of EPM to WiDr cells was mediated by cell apoptosis. This extract was potential to be developed as chemopreventive agent.

Arecoline, the main alcaloid of Areca cathecu L has been proven to posses cytotoxic activity against various cancer cell lines. The research conducted to examine the cytotoxic activity of arecoline alone and its combination with doxorubicin against HeLa cervical cancer cell line. Single treatment of arecoline in various concentration on HeLa cancer cell were done followed by the combinational treatment with doxorubicin. The cell viability as the parameter of cytotoxicity was measured using MTT (3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazolium bromide) assay. The apoptotic effect was examined by double staining assay using etidium bromide-acridin orange. Arecoline did not show potent cytotoxicity effect against HeLa since the value of IC50 is 462 µM. The combinational treatment of arecoline and doxorubicin showed synergicity with the optimum CI value is 0.48 given by the treatment of 30mM arecoline combined with 125 nM doxorubicin. The result of this study shows that arecoline has potential to be proposed as co-chemotherapeutic agent for cervical cancer. However, further study on its molecular mechanism needs to be conducted.