Background: The putative pharmacophore of a naturally cytotoxic limonoid haperforin B1, E-5-iodomethylene-6,6-dimethyl-5,6-dihydropyran-2-one (IDDP) was synthesized and its biological activity was investigated.
Materials and methods: The cytotoxicity of IDDP was assessed using human breast, lung, colorectal and epidermal carcinomas, chronic myeloid leukemia and glioblastoma cell lines. Cell cycle analysis was performed by flow cytometry. The induction of apoptosis was studied by a caspase assay and by annexin V-propidium iodide double staining. The organization of actin and tubulin microfilaments was analysed by immunocytochemical labeling.
Results: IDDP was shown to inhibit the growth of a panel of human cancer cell lines independently of their p53 status with IC(50) ranging from 0.07 to 0.50 microM. All the treated cells were arrested in the G(2)/M phase in a time-dependent manner before cell death occurred through an apoptotic pathway. Immunocytochemical studies revealed that the normal organization of microfilaments and microtubules was disrupted in IDDP exposed cells.
Conclusion: IDDP can be considered as a promising anticancer agent.