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

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

  • Cancers (Basel). 2023 Sep 6;15(18):4442. doi: 10.3390/cancers15184442.
Beata Marciniak 1,  Mateusz Kciuk 1 2,  Somdutt Mujwar 3,  Rajamanikandan Sundaraj 4,  Karol Bukowski 1,  Renata Gruszka 1
Affiliations

Affiliations

  • 1 Department of Molecular Biotechnology and Genetics, University of Lodz, Banacha 12/16, 90-237 Lodz, Poland.
  • 2 Doctoral School of Exact and Natural Sciences, University of Lodz, 90-237 Lodz, Poland.
  • 3 Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India.
  • 4 Centre for Drug Discovery, Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India.
PMID: 37760412 DOI: 10.3390/cancers15184442
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.

Keywords

BCI; apoptosis; cytotoxicity; dual specificity phosphatase 6 (DUSP6); irinotecan; oxaliplatin.

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