Suillus collinitus methanolic extract increases p53 expression and causes cell cycle arrest and apoptosis in a breast cancer cell line.

In the present work, methanolic, ethanolic and boiled water extracts of Suillus collinitus were chemically characterised and submitted to an evaluation of their bioactive properties (antioxidant potential and cytotoxic activity in tumor cell lines). Phenolic acids and sugars were identified chromatographically and quantified in the methanolic and boiled water extracts, respectively. S. collinitus ethanolic extract had the highest antioxidant activity. Nevertheless, with respect to cell growth inhibition, the methanolic extract was the most potent extract, particularly in MCF-7 cells (GI(50) 25.2±0.2 µg/ml). Moreover, the GI(50) concentration of this extract induced a G1 cell cycle arrest, with a concomitant decrease in the percentage of cells in the S phase. Furthermore, it caused an increase in the percentage of apoptotic cells, from 6.0±0.2% in untreated cells, to 15.3±2.0% in cells treated with the GI(50) concentration and to 16.3±2.0% in cells treated with 2×GI(50) concentration. In addition, 48 h treatment with the GI(50) concentration caused a strong increase in the levels of p53, p21, and cleaved PARP, together with a decrease in Bcl-2 and XIAP. Results indicate that S. collinitus may be a promising source of bioactive compounds. Particularly, its methanolic extract appears to have a p53-mediated effect on the normal cell cycle distribution and apoptosis induction in a human breast tumor cell line.

Simultaneous targeting of P-gp and XIAP with siRNAs increases sensitivity of P-gp overexpressing CML cells to imatinib.

It is accepted that cancer chemoresistance may be due to overexpression of antiapoptotic proteins or P-gp. This study investigated the effect of downregulation of X-chromosome-linked inhibitor of apoptosis (XIAP) and of simultaneous downregulation of XIAP and P-gp on sensitivity to imatinib. The K562 and K562Dox (P-gp overexpressing) chronic myeloid leukemia cell lines were used and downregulation of target proteins was achieved with siRNAs. Targeting XIAP moderately enhanced sensitivity to imatinib in both cell lines. Simultaneous targeting of XIAP and P-gp further enhanced sensitivity to imatinib in the resistant K562Dox cells. In conclusion, simultaneous targeting of P-gp and XIAP increases sensitivity of P-gp overexpressing chronic myeloid leukemia cells to imatinib.