Kim Hee Young, Moon Jeong Yong, Cho Somi Kim
Interdisciplinary Graduate Program in Advanced Convergence Technology and Science, Jeju National University, Jeju, Korea.
Subtropical/Tropical Organism Gene Bank, Jeju National University, Jeju, Korea.
J Med Food. 2023 Mar;26(3):201-210. doi: 10.1089/jmf.2022.K.0061. Epub 2023 Jan 30.
Odd-chain saturated fatty acids generally serve as specific biomarkers of dietary components and dairy intake, some of which have anticancer properties. This study was performed to assess the anticancer effects of heptadecanoic acid (HDNA) in human pancreatic carcinoma cells. MTT (thiazolyl blue tetrazolium bromide) assay showed that HDNA exerted stronger cytotoxic effects than pentadecanoic acid, palmitic acid (16:0), stearic acid (18:0), oleic acid (18:1), and linoleic acid (18:2) on both Panc-1 and MIA PaCa-2 pancreatic cancer cells. In addition, HDNA reduced colony formation and induced apoptosis in these pancreatic cancer cells as indicated by Hoechst 33342 staining, Annexin V/propidium iodide staining, cell cycle analysis, and Western blotting analysis in a dose-dependent manner. Moreover, HDNA synergistically reduced cell viability and promoted apoptosis when combined with gemcitabine (GEM), a chemotherapeutic agent commonly used in the treatment of pancreatic cancer. GEM-resistant MIA PaCa-2 (GR-MIA PaCa-2) cells with a resistance indices (RI) value of 215.09 [RI = half-maximal inhibitory concentration (IC) of GR-MIA PaCa-2 cells/IC of MIA PaCa-2 cells] were established, and the efficacy of HDNA on GEM chemosensitivity was confirmed. Surprisingly, HDNA exhibited even higher antiproliferative efficacy against GR-MIA PaCa-2 cells (IC = 71.45 ± 6.37 M) than parental MIA PaCa-2 cells (IC = 77.47 ± 2.10 M). Finally, HDNA treatment inhibited the Hippo pathway and induced apoptosis of GR-MIA PaCa-2 cells. These findings suggest the beneficial effects of a HDNA-rich diet during pancreatic cancer treatments.
奇数链饱和脂肪酸通常作为饮食成分和乳制品摄入量的特定生物标志物，其中一些具有抗癌特性。本研究旨在评估十七烷酸（HDNA）对人胰腺癌细胞的抗癌作用。MTT（噻唑蓝四氮唑溴盐）试验表明，HDNA对Panc-1和MIA PaCa-2胰腺癌细胞的细胞毒性作用比十五烷酸、棕榈酸（16:0）、硬脂酸（18:0）、油酸（18:1）和亚油酸（18:2）更强。此外，Hoechst 33342染色、膜联蛋白V/碘化丙啶染色、细胞周期分析和蛋白质印迹分析表明，HDNA以剂量依赖的方式减少了这些胰腺癌细胞的集落形成并诱导了凋亡。此外，当HDNA与吉西他滨（GEM）联合使用时，GEM是一种常用于治疗胰腺癌的化疗药物，HDNA可协同降低细胞活力并促进凋亡。建立了耐药指数（RI）值为215.09 [RI = GR-MIA PaCa-2细胞的半数最大抑制浓度（IC）/MIA PaCa-2细胞的IC]的吉西他滨耐药MIA PaCa-2（GR-MIA PaCa-2）细胞，并证实了HDNA对吉西他滨化疗敏感性的疗效。令人惊讶的是，HDNA对GR-MIA PaCa-2细胞（IC = 71.45 ± 6.37 μM）的抗增殖效力甚至高于亲代MIA PaCa-2细胞（IC = 77.47 ± 2.10 μM）。最后，HDNA处理抑制了Hippo通路并诱导了GR-MIA PaCa-2细胞的凋亡。这些发现表明，在胰腺癌治疗期间，富含HDNA的饮食具有有益作用。
