Differential effects of docosahexaenoic acid (DHA) and linoleic acid (LA) on miR-101 and miR-342 tumor suppressor microRNAs in Taxol-treated HER2-positive breast cancer cells.

Background & Aims: Docosahexaenoic acid (DHA) and linoleic acid (LA) have been shown to exhibit anti-proliferative effects against breast cancer cells. However, the mechanisms underlying these effects are not yet fully understood. One potential mechanism is through the regulation of microRNAs (miRs), which are known to play a crucial role in breast cancer development and progression. This study aimed to investigate the expression of miR-342 and miR-101 as tumor-suppressor miRs in the human HER-2 positive breast cancer cell line BT-474 after treatment with DHA, LA, alone or in combination with Taxol, a standard chemotherapy agent.
Methods: The human breast cancer cell line BT-474 was cultured, and the IC50 for Taxol was determined using the MTT assay. Cells were then cultured and treated for 24 h with 100 μM DHA and 50 μM LA, alone or in combination with the respective IC50 of Taxol. Cells were harvested, and miRNA extraction and cDNA synthesis were performed using standard methods. Expression levels of miRs were analyzed using quantitative real-time PCR (qRT-PCR), and results were normalized against U6 snRNA expression levels.
Results: The Taxol IC50 for BT-474 cells was 19 nM. According to the data obtained from our study, it was observed that Taxol treatment resulted in the down-regulation of both miR-101 and miR-342 (3.69 (p < 0.0001) and 1.88 fold, (p < 0.0001) respectively). In addition, DHA, LA and DHA + LA caused up-regulation of miR-101 (0.11, 0.05, 0.03 fold (p < 0.0001) respectively) but not miR-342 (decreased by 1.93 (p < 0.0001), 2.89 (p < 0.0001) and 1.19 fold (p = 0.0029) respectively). Notably, treatment with DHA, LA and DHA + LA was able to restore the down-regulated expression of miR-101 (0.25 (p < 0.0001), 0.05 (p = 0.0012) and 0.06 fold (p < 0.0001) respectively) during Taxol treatment.
Conclusion: Our study demonstrates that DHA and LA can effectively compensate for the reduced expression of miR-101 during Taxol treatment. These findings suggest that dietary fatty acids may play a critical role in modulating the anti-cancer effects of chemotherapy agents. Future studies are needed to investigate the functional aspects of dietary fatty acids on breast cancer development and progression.
Competing Interests: Declaration of competing interest None declared.
(Copyright © 2024. Published by Elsevier Ltd.)