Abstract
Saturated fatty acids possess few health benefits compared to unsaturated fatty acids. However, increasing experimental evidence demonstrates the nutritionally beneficial role of odd-chain saturated fatty acids in human health. In this study, the anti-cancer effects of pentadecanoic acid were evaluated in human breast carcinoma MCF-7/stem-like cells (SC), a cell line with greater mobility, invasiveness, and cancer stem cell properties compared to the parental MCF-7 cells. Pentadecanoic acid exerted selective cytotoxic effects in MCF-7/SC compared to in the parental cells. Moreover, pentadecanoic acid reduced the stemness of MCF-7/SC and suppressed the migratory and invasive ability of MCF-7/SC as evidenced by the results of flow cytometry, a mammosphere formation assay, an aldehyde dehydrogenase activity assay, and Western blot experiments conducted to analyze the expression of cancer stem cell markers—CD44, β-catenin, MDR1, and MRP1—and epithelial–mesenchymal transition (EMT) markers—snail, slug, MMP9, and MMP2. In addition, pentadecanoic acid suppressed interleukin-6 (IL-6)-induced JAK2/STAT3 signaling, induced cell cycle arrest at the sub-G1 phase, and promoted caspase-dependent apoptosis in MCF-7/SC. These findings indicate that pentadecanoic acid can serve as a novel JAK2/STAT3 signaling inhibitor in breast cancer cells and suggest the beneficial effects of pentadecanoic acid-rich food intake during breast cancer treatments.
Highlights
According to the latest cancer statistics, breast cancer ranks as the leading cause of mortality among women [1]
We demonstrate that pentadecanoic acid suppresses the stemness and induces apoptosis through targeting the JAK2/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway
Consistent with the previous reports describing that STAT3 can be phosphorylated by the IL-6-stimulated JAK2 [94,95], our results show that IL-6 exposure significantly induced pJAK2 and pSTAT3 expression in MCF-7/stem-like cells (SC)
Summary
According to the latest cancer statistics, breast cancer ranks as the leading cause of mortality among women [1]. Surgery, chemotherapy, hormone therapy, and radiotherapy are widely used to treat breast cancer patients [2]. Convincing evidence demonstrates that the presence of a small subpopulation cells, called breast cancer stem cells (BCSCs), play a pivotal role in breast cancer therapy resistance [3,4], metastasis, and tumor recurrence [5]. BCSCs are known to express higher levels of drug efflux transporters such as P-glycoprotein (P-gp/ABCB1) and multidrug resistance-associated protein 1. CD44, CD24, CD133, EpCAM, CD166, CD47, aldehyde dehydrogenases (ALDH), and ABCG2 have been identified as key BCSC markers [7,8,9,10].
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