Triterpenes from Pholiota populnea as Cytotoxic Agents and Chemosensitizers to Overcome Multidrug Resistance of Cancer Cells.

The detailed mycochemical analysis of the n -hexane extract of Pholiota populnea led to the isolation of four new lanostane diesters, named pholiols A-D ( 1 - 4 ), together with an acyclic triterpene, (3 S ,6 E ,10 E ,14 E ,18 E ,22 S )-2,3,22,23-tetrahydroxy-2,6,10,15,19,23-hexamethyl-6,10,14,18-tetracosatetraene ( 5 ), ergosterol ( 6 ), and 3β-hydroxyergosta-7,22-diene ( 7 ). The isolation was carried out by multistep flash chromatography, and the structures were elucidated using extensive spectroscopic analyses, including 1D and 2D NMR and MS measurements. The isolated metabolites ( 1 - 6 ) were investigated for cytotoxic activity against Colo205 and Colo320 colon adenocarcinoma and nontumoral MRC-5 cell lines. Among the tested compounds, ergosterol ( 6 ) showed substantial cytotoxic activity against all cell lines with IC 50 values of 4.9 μM (Colo 205), 6.5 μM (Colo 320), and 0.50 μM (MRC) with no tumor cell selectivity. A P-glycoprotein efflux pump modulatory test on resistant Colo320 cells revealed that pholiols A ( 1 ) and B ( 2 ) and linear triterpene polyol 5 have the capacity to inhibit the efflux-pump overexpressed in the cells. Moreover, the drug interactions of triterpenes with doxorubicin were studied by the checkerboard method on Colo 320 cells. Pholiols B ( 2 ) and D ( 4 ) interacted in synergistic and acyclic triterpene 5 in a very strong synergistic manner; the combination index (CI) values at 50% of the growth inhibition dose (ED 50 ) were found to be 0.348, 0.660, and 0.082, respectively. Our results indicate that P. populnea is a promising source for finding new triterpenes with significant chemosensitizing activity on cancer cells.