In Vitro and In Silico Investigation of BCI Anticancer Properties and Its Potential for Chemotherapy-Combined Treatments

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2023 Sep 28

PMID 37760412

Authors

Beata Marciniak

Mateusz Kciuk

Somdutt Mujwar

Rajamanikandan Sundaraj

Karol Bukowski

Renata Gruszka

Affiliations

Soon will be listed here.

Abstract

Background: DUSP6 phosphatase serves as a negative regulator of MAPK kinases involved in numerous cellular processes. BCI has been identified as a potential allosteric inhibitor with anticancer activity. Our study was designed to test the anticancer properties of BCI in colon cancer cells, to characterize the effect of this compound on chemotherapeutics such as irinotecan and oxaliplatin activity, and to identify potential molecular targets for this inhibitor.

Methods: BCI cytotoxicity, proapoptotic activity, and cell cycle distribution were investigated in vitro on three colon cancer cell lines (DLD1, HT-29, and Caco-2). In silico investigation was prepared to assess BCI drug-likeness and identify potential molecular targets.

Results: The exposure of colorectal cancer cells with BCI resulted in antitumor effects associated with cell cycle arrest and induction of apoptosis. BCI exhibited strong cytotoxicity on DLD1, HT-29, and Caco-2 cells. BCI showed no significant interaction with irinotecan, but strongly attenuated the anticancer activity of oxaliplatin when administered together. Analysis of synergy potential further confirmed the antagonistic interaction between these two compounds. In silico investigation indicated CDK5 as a potential new target of BCI.

Conclusions: Our studies point to the anticancer potential of BCI but note the need for a precise mechanism of action.

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