Anti-tumor activity of Annona squamosa seeds extract containing annonaceous acetogenin compounds.

ETHNOPHARMACOLOGICAL RELEVANCE: Seeds of Annona squamosa L. have been used in the south of China as a folk remedy to treat "malignant sores" (cancer). AIM OF THE STUDY: To investigate the chemical constituents and the anti-tumor activity of the standardized A. squamosa seeds extract in vitro and in vivo. MATERIALS AND METHODS: Annonaceous acetogenin profiles of the standardized extract were determined by using Fourier transform infrared (FT-IR) and high performance liquid chromatography (HPLC) techniques. The anti-tumor activity of the extract was tested by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity in vitro and H(22) hepatoma cells transplantation tumor model in vivo. RESULTS: The FT-IR spectroscopy showed the presence of annonaceous acetogenin compounds in the extract. Two major annonaceous acetogenins: 12, 15-cis-squamostatin-A and bullatacin were identified and quantified by HPLC. The seed extract showed significant anti-tumor activity against four human tumor cell lines, especially for MCF-7 (IC(50). 0.25 µg/ml) and Hep G2 (IC(50). 0.36 µg/ml) cells in vitro. The extract inhibited the growth of H(22) tumor cells in mice with a maximum inhibitory rate of 69.55% by oral administration. CONCLUSION: A. squamosa seed extract showed significant anti-tumor activities against human hepatoma cells in vitro and in vivo, indicating a potential for developing the extract as a novel anti-liver cancer drug.

Antitumor activity of annonaceous acetogenins in HepS and S180 xenografts bearing mice.

Annonaceous acetogenins (ACGs), as one of the most powerful groups of mitochondrial complex I inhibitors, exhibit potent cytotoxic activity against a variety of human tumor cell lines. In this study, the antitumor activities of three main types of ACGs were investigated using S180 and HepS xenografts bearing mice simultaneously. The results revealed that select ACGs suppressed tumor growth in a dose-dependent fashion. Tested ACGs showed more selective antitumor activity against HepS. Furthermore, adjacent bis-THF ACGs were more active than mono-THF and nonadjacent bis-THF ACGs against HepS and S180; nonadjacent bis-THF ACGs were more active than mono-THF ACGs against S180, but mono-THF ACGs were more potent than nonadjacent bis-THF ACGs against HepS.