Antitumor Activity of Pisosterol in Mice Bearing with S180 Tumor

Abstract

Triterpenes are products of secondary metabolism of different organisms, being very common in fungus species. One single fungus' specie can produce a high number of active compounds, with different pharmacological effects.1) Gamoderma lucidum, as an example, produces over 120 different triterpenes, and also other bioactive compounds.2) Several species has been studied for their biological activities, such as antiviral, anticomplement, antiatherogenic, antitumour and hepatoprotective activities. 1)Pisosterol (Fig. 1), a triterpene isolated from the ectomicorhizal Pisolithus tinctorius, has been reported to strongly inhibit tumor cells proliferation in vitro, while it had no antimitotic effect on sea urchin eggs.3) Classical cytotoxic drugs tested in the sea urchin eggs and cancer cells have shown to be active in both assays, although compounds may present a higher IC 50 value in the sea urchin eggs than in tumor cells, as observed for doxorubicin and etoposide. 4,5) The sea urchin eggs assay can detect cytotoxic agents such as DNA synthesis inhibitors, RNA synthesis inhibitors, microtubule assembly inhibitors, and protein synthesis inhibitors. 6)Thus, the absence of activity of pisosterol in this assay suggested a different mechanism of action. In fact, Montenegro et al. (2007) 7) demonstrated that the inhibition of leukemia (HL-60) cells proliferation is related to monocytic cell-like differentiation induction, followed by apoptosis. These findings may explain the selectivity of pisosterol to cancer cells, and reinforce the anticancer potential of this naturally occurring substance.In the present study, the in vivo antitumor activity of pisosterol was evaluated using sarcoma 180 transplanted in mice. Histopathological and morphological analyses of the tumor and organs, including liver, spleen and kidney were performed in order to evaluate the toxicological aspects of the pisosterol treatment. MATERIALS AND METHODSPisosterol Isolation Pisosterol, in its pure form, was isolated from the ectomicorhizal fungus Pisolithus tinctorius collected in a Eucalyptus plantation at Brejo, Maranhão, Northeast Brazil as described previously.3)The structure of pisosterol ( Melo, 1127, P.O. Box 3157, 60430-270 Fortaleza, Ceará, Brasil: b Departamento de Clínica Odontológica, Universidade Federal do Ceará; and c Departamento de Química Orgânica e Inorgânica, Universidade Federal do Ceará; Fortaleza, Ceará, Brasil. Received August 31, 2007; accepted December 5, 2007 It has been reported that pisosterol was active against cancer cells but lacked activity on the development of sea urchin eggs. Recently, it was reported that pisosterol induces differentiation in leukemia cell line. The present study evaluated the in vivo antitumor activity of pisosterol a triterpene isolated from Pisolithus tinctorius. Histopathological and morphological analyses of the tumor and the organs, including liver, spleen and kidney, were performed in order to evaluate toxicological aspects associated with pisosterol treatments. Antitumor activity of...

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