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.
Original language | English (US) |
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Article number | 193 |
Journal | 3 Biotech |
Volume | 13 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2023 |
Externally published | Yes |
Keywords
- 5-Fluorouracil
- 5-Fluorouracil-resistant MDA-MB 231 cell (5-FUR/MDA-MB 231)
- Pterostilbene–isothiocyanate (PTER–ITC)
- Tamoxifen
- Tamoxifen-resistant MCF-7 cell (TR/MCF-7)
- miRNA immunoprecipitation (miR-IP)
ASJC Scopus subject areas
- Biotechnology
- Environmental Science (miscellaneous)
- Agricultural and Biological Sciences (miscellaneous)