Antitumor activity of pisosterol in mice bearing with S180 tumor.

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 pisosterol (50 or 100 mg/m2) was confirmed in mice bearing Sarcoma 180 tumor cells. The tumor growth inhibition ratios were 43.0% and 38.7% for mice treated with pisosterol at 50 and 100 mg/m2, respectively. Histopathological analysis of liver, kidney and spleen was also evaluated. Liver and kidney were the major affected organs by pisosterol, although the observed alterations can be considered reversible.

Pisosterol induces monocytic differentiation in HL-60 cells.

The aim of this study was to determine whether the antiproliferative effects observed for pisosterol, a cytotoxic triterpene isolated from Pisolithus tinctorius, are related to cell differentiation induction using HL-60 cell line as a model. Also, the effects of pisosterol on normal human cells were examined in peripheral blood mononuclear cells (PBMC). The effects on cell viability and morphological changes were the first indications showing that pisosterol induces HL-60 differentiation. The demonstration of blue tetrazolium reduction in HL-60 cells exposed to pisosterol demonstrated differentiation in a dose- and time-dependent manner, reaching a maximum effect after 72 h incubation at 5 microg/mL. Assays for alpha-naphthyl acetate esterase activity indicated that pisosterol triggers differentiation towards a monocytic cell-like pathway. The antiproliferative effect of pisosterol was determined by inhibition of DNA synthesis based on BrdU incorporation into HL-60 proliferating cells. It appears that pisosterol-treated cells, despite displaying a differentiated phenotype, continued to proliferate at all doses tested after 72 h, with a slightly decrease at 5 microg/mL. Apoptosis was observed in pisosterol-treated cells in a dose-dependent way. Nevertheless, after the same period of incubation, no cytotoxicity was detected in PBMC in the presence of pisosterol even at 25 microg/mL, providing some evidence that pisosterol may be selective for tumor cells. The mechanisms underlying the effect of pisosterol in leukemia cells indicates the induction of a monocytic cell-like differentiation, suggesting that this compound could be used in the development of new pharmacological tools with potential therapeutic value in the management of leukemia with fewer side effects.

Cytotoxic activity of pisosterol, a triterpene isolated from Pisolithus tinctorius (Mich.: Pers.) Coker & Couch, 1928.

Pisolithus tinctorius (Basidiomycete) is an ectomicorrhizal fungus found in the roots and soil surrounding of many species of eucalyptus and pine trees. The present work verified the cytotoxic potential of pisosterol, a triterpene isolated from P. tinctorius collected in the Northeast region of Brazil, on three different animal cell models: mouse erythrocytes, sea urchin embryos and tumor cells. Pisosterol lacked activity on mouse erythrocytes as well as on the development of sea urchin eggs, but strongly inhibited the growth of all seven tumor cell lines tested, especially the leukemia and melanoma cells (IC50 of 1.55, 1.84 and 1.65 microg/ ml for CEM, HL-60 and B16, respectively). The results found for pisosterol were compared with those of doxorubicin and etoposide.