Antitumor constituents from Annona squamosa fruit pericarp

Pharmacologically safe compounds that can inhibit the proliferation of tumor cells have potential as anticancer agents. Annonaceae seems to be one of the least chemically as well as pharmacologically known families compared with its large size. Earlier studies on Annona species have showed that this family is a potent source of a wide variety of secondary metabolites belonging to several categories. The chemistry and anti-inflammatory effects of the seed oils of Annona species have been studied and published. Several antibacterial and anti-inflammatory kaurane-type diterpenes were isolated and identified, and biological evaluations were also carried out and published. The pesticidal activity of various extracts has been reported and their formulations have been tested against a wide spectrum of pests of national importance. Flowers of some Annonaceae are used in perfumery and many members of this family are used in folk medicine of some tropical countries to treat various types of cancers and tumors. In the present study we used various solvent extracts of Annona squamosa fruit pericarp to test for cytotoxic activity using in vitro cultures of Dalton's lymphoma cells as well as HeLa cells. Cytotoxicity was detected by the Trypan blue exclusion test and induction of apoptosis was evaluated by [3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide] assay (MTS assay) and DNA ladder assay. The chloroform extract of Annona squamosa pericarp was found to be cytotoxic to the different cell lines tested. The inhibitory concentration required for 50% cytotoxicity (IC50) was also determined. The bioactivity-directed isolation yielded two kaurane-type diterpenes, (-)-ent-kaur-16-en-19-oic acid and 16 alpha,17-dihydroxy-ent-kauran-19-oic acid. This study suggests the potential of Annonna squamosa fruit pericarp for the development of modern medicine for the treatment of cancers.