Investigating mushroom LMW compounds as potential Bcl-2 inhibitors: docking studies using AutoDock4
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abstract
The B cell CLL/lymphoma-2 (Bcl-2) family is functionally classified as either anti-apoptotic
or pro-apoptotic, and the regulation of its interactions dictates survival or commitment to
apoptosis. Bcl-2 family is also implicated in a wide range of diseases. In some types of
cancers, including lymphomas and epithelial cancers, protein overexpression of anti-apoptotic
Bcl-2 family, such as the Bcl-2 protein is indicative of cancer in an advanced stage, with a
poor prognosis and resistant to chemotherapy [1]. Several reports indicate that mushrooms
have the ability to promote apoptosis in tumour cell lines, but the mechanism of action is not
fully understood. Inhibition of the interaction between Bcl-2 (anti-apoptotic protein) and proapoptotic
proteins could be an important step in the mechanism of mushroom induced
apoptosis. Therefore, the discovery of compounds with the capacity to inhibit Bcl-2 is an
ongoing research topic on cancer therapy.
In this work, docking studies were performed using a dataset of 40 low molecular weight
(LMW) compounds present in mushrooms. The docking software AutoDock 4 was used and
docking studies were performed using 5 selected Bcl-2 crystal structures as targets.
Compounds with the lowest predicted binding energy (predΔG) are expected to be the more
potent inhibitors. Among the tested compounds, steroids presented the lowest predΔG with
several exhibiting values below -9 kcal/mol. The results are corroborated by several reports
that state that steroids induce apoptosis in several tumor cells. It is thus feasible that they
might act by preventing Bcl-2 from forming complexes with the respective proapoptotic
protein interaction partners, namely Bak, Bax, and Bim. Moreover, previous studies on our
research group demonstrated that 48 h treatment of MCF-7 cells (breast carcinoma) with
Suillus collinitus methanolic extract caused a decrease in Bcl-2, highlighting the antitumor
potential of this mushroom species [2].
In conclusion, the process of apoptosis promoted by mushroom extracts may be related to the
inhibition of Bcl-2 by the steroid derivatives herein studied. However, further studies are
needed to confirm this hypothesis.
