Abstract
Converging evidences identifies that microRNA-21 (miR-21) is responsible for drug resistance in breast cancer. This study aims to evaluate the miR-21-modulatory potential of a hybrid compound, pterostilbene–isothiocyanate (PTER–ITC), in tamoxifen-resistant MCF-7 (TR/MCF-7) and 5-fluorouracil-resistant MDA-MB 231 (5-FUR/MDA-MB 231) breast cancer cell lines, established by repeated exposure to gradually increasing the concentrations of tamoxifen and 5-fluorouracil, respectively. The outcome of this study shows that PTER–ITC effectively reduced the TR/MCF-7 (IC50: 37.21 µM) and 5-FUR/MDA-MB 231 (IC50: 47.00 µM) cell survival by inducing apoptosis, inhibiting cell migration, colony and spheroid formations in TR/MCF-7 cells, and invasiveness of 5-FUR/MDA-MB 231 cells. Most importantly, PTER–ITC significantly reduced the miR-21 expressions in these resistant cell lines. Moreover, the downstream tumor suppressor target gene of miR-21 such as PTEN, PDCD4, TIMP3, TPM1, and Fas L were upregulated after PTER–ITC treatment, as observed from transcriptional (RT-qPCR) and translational (immunoblotting) data. In silico and miR-immunoprecipitation (miR-IP) results showed reduced Dicer binding to pre-miR-21, after PTER–ITC treatment, indicating inhibition of miR-21 biogenesis. Collectively, the significance of this study is indicated by preliminary evidence for miR-21-modulatory effects of PTER–ITC that highlights the potential of this hybrid compound as an miR-21-targeting therapeutic agent.
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The authors would like to convey their sincere thanks to the Council for Scientific and Industrial Research (CSIR), Government of India, for providing research fellowship [9/143(0897)/2017-EMR-I] to VK. The authors acknowledge the non-academic and technical support from the departmental offices of Department of Bioscience and Bioengineering and Sponsored Research and Industrial Consultancy of Indian Institute of Technology Roorkee, India.
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This work was supported by a research grant from the Department of Biotechnology, Government of India (Grant No. BT/PR12138/MED/97/238/2014) to PR.
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VK: conceptualization, methodology, formal analysis and investigation, validation, data curation, visualization, writing—original draft preparation; SH: methodology, formal analysis and investigation, visualization; SS: methodology, visualization; SG: methodology, imaging, formal analysis and investigation; PD: methodology, formal analysis and investigation, visualization; PR: conceptualization, formal analysis and investigation, data curation, writing—review and editing, funding acquisition, resources, supervision.
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Kumar, V., Haldar, S., Saini, S. et al. Pterostilbene–isothiocyanate reduces miR-21 level by impeding Dicer-mediated processing of pre-miR-21 in 5-fluorouracil and tamoxifen-resistant human breast cancer cell lines. 3 Biotech 13, 193 (2023). https://doi.org/10.1007/s13205-023-03582-3
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DOI: https://doi.org/10.1007/s13205-023-03582-3