Pentadecanoic Acid, an Odd-Chain Fatty Acid, Suppresses the Stemness of MCF-7/SC Human Breast Cancer Stem-Like Cells through JAK2/STAT3 Signaling

• Published in: Nutrients Vol. 12; no. 6; p. 1663
• Main Authors: To, Ngoc Bao, Nguyen, Yen Thi-Kim, Moon, Jeong Yong, Ediriweera, Meran Keshawa, Cho, Somi Kim
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.06.2020; MDPI
• Subjects: aldehyde dehydrogenase; Antibodies; antineoplastic activity; Antineoplastic Agents; Apoptosis; Apoptosis - genetics; assays; ATP Binding Cassette Transporter, Subfamily B - metabolism; beta Catenin - metabolism; Biomarkers, Tumor - metabolism; Breast cancer; breast neoplasms; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cancer therapies; Cell culture; Cell cycle; cell cycle checkpoints; Cell Transformation, Neoplastic - drug effects; Cell Transformation, Neoplastic - genetics; cytotoxicity; Drug resistance; Epithelial-Mesenchymal Transition - genetics; Fatty acids; Fatty Acids - pharmacology; Flow cytometry; food intake; human cell lines; human health; Humans; Hyaluronan Receptors - metabolism; interleukin-6; Janus Kinase 2 - metabolism; Kinases; Matrix Metalloproteinase 9 - metabolism; MCF-7 Cells; migratory behavior; Milk; neoplasm cells; nutrients; Penicillin; Proteins; saturated fatty acids; Signal Transduction - drug effects; Signal Transduction - genetics; slugs; Snail Family Transcription Factors - metabolism; STAT3 Transcription Factor - metabolism; stem cells; Tumorigenesis; unsaturated fatty acids; Western blotting; Canada; United States > US; pentadecanoic acid; apoptosis; breast cancer; cancer stem cells; odd-chain fatty acids; JAK2/STAT3 signaling
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu12061663

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.