Strebloside, a Constituent of Streblus asper with Antineoplastic Activity

Moraceae is a family of flowering plants distributed in tropical and subtropical regions, of which the genus Streblus contains about 25 species [1]., Streblus asper Lour. is used medicinally, and several cardiac glycosides have been characterized as cytotoxic components from this species [2,3]. In a search for anticancer agents from higher plants, a chloroform-soluble extract of the stem bark of S. asper collected in Vietnam was found to be highly cytotoxic toward the HT-29 human colon cancer cell line. Three new (3'-demethylkamaloside, 19-hydroxykamaloside, and 6'-hydroxykamaloside) and two known (3-O-β-D-fucopyranosylperiplogenin and strebloside) cardiac glycosides were isolated from this plant sample, with six new and two known analogues being synthesized from strebloside [4]. The structures of all compounds obtained were determined by analysis of their spectroscopic data, with all isolates found to be potently active against HT-29 cells. When tested against CCD-112CoN normal human colon cells, strebloside did not show any discernible activity. On evaluation for its cytotoxicity toward the human MV4 – 11, THP-1, and Kasumi-1 leukemia cell lines, strebloside was found to be highly cytotoxic, but showed little toxicity toward normal human peripheral blood mononuclear cells. Strebloside was also cytotoxic against the MDA-MB-231 human breast and OVCAR3 human ovarian cancer cell lines. When evaluated in a murine in vivo hollow fiber assay against these two cell lines, strebloside (ip, 5 mg/kg/day, four days) showed significant cell growth inhibition, with no side effects observed in mice at any of the doses used. Mechanistic studies showed that strebloside mediates its cytotoxicity through induction of tumor cell apoptosis, as indicated by its blocking cell progression through the cell cycle at the G2-phase and inducing PARP cleavage in OVCAR3 cells.