Antiproliferative effects of isoprenoids from Sarcophyton glaucum   on breast cancer MCF-7 cells

Purpose: To evaluate the anticancer activity of isoprenoids of Sarcophyton glaucum on MCF-7 cells and to investigate the potential synergistic effect of doxorubicin.
Methods: Isolation and purification of isoprenoids were performed by applying different planar chromatographic methods (CC and PTLC). Further analyses of the isoprenoids by nuclear magnetic resonance (NMR) and mass spectrometry (MS) carried out to identify the compounds. Sulforhodamine-B (SRB) assay was used to determine the cytotoxic activity of the compounds against the MCF-7 human cell line. Flow cytometric analysis was used to assess their impact on cell cycle of MCF-7. Combination index (CI), when the compounds were combined with doxorubicin, was calculated to determine possible synergism. The isoprenoid compounds were also incubated at ¼ or ½ of their respective half-maximal concentration (IC₅₀) with equimolar concentrations of doxorubicin.
Results: Four known isoprenoid derivatives (1-4) were identified as 10(14)-aromadendrene (1), sarcophinediol (2), ent-deoxysarcophine (3) and sarcotrocheliol acetate (4). It was observed that cells accumulated in pre-G phase as well. CI of compound 3 with doxorubicin was 0.67 and 0.79, respectively, at ¼ and ½ of IC₅₀, indicating overt synergism. This was confirmed by re-assessing the cell cycle stages of MCF-7 cells.
Conclusion: The results indicate that compound 3 exhibits promising cytotoxicity as well as synergism with doxorubicin in MCF-7 cells. This is attributed, at least partly, to its ability to generate intercellular apoptosis induction.

Keywords
Sarcophyton glaucum; Combination index; Antiproliferation; Isoprenoidal derivatives; 10(14)-Aromadendrene; Sarcophinediol; Deoxysarcophine; Sarcotrocheliol acetate; Doxorubicin