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 2020-06, Vol.12 (6), p.1663
• Main Authors: To, Ngoc Bao, Nguyen, Yen Thi-Kim, Moon, Jeong Yong, Ediriweera, Meran Keshawa, Cho, Somi Kim
• Format: Article
• Language: English
• Subjects: Aldehyde dehydrogenase; Aldehydes; Antibodies; Antineoplastic Agents; Apoptosis; Apoptosis - genetics; ATP Binding Cassette Transporter, Subfamily B - metabolism; beta Catenin - metabolism; Biomarkers, Tumor - metabolism; Breast cancer; Breast carcinoma; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; cancer stem cells; Cancer therapies; Caspase; CD44 antigen; Cell culture; Cell cycle; 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; G1 phase; Gelatinase A; Gelatinase B; Humans; Hyaluronan Receptors - metabolism; Interleukin 6; Invasiveness; JAK2/STAT3 signaling; Janus kinase 2; Janus Kinase 2 - metabolism; Kinases; Markers; Matrix Metalloproteinase 9 - metabolism; MCF-7 Cells; MDR1 protein; Mesenchyme; Milk; odd-chain fatty acids; Penicillin; pentadecanoic acid; Proteins; Signal Transduction - drug effects; Signal Transduction - genetics; Snail Family Transcription Factors - metabolism; Stat3 protein; STAT3 Transcription Factor - metabolism; Stem cells; Tumorigenesis; β-Catenin
• 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.