Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines

doi:10.16352/j.issn.1001-6325.2024.04.0440

Abstract

Abstract: Objective To study the effect of carboxyamidotriazole-orotate(CTO) on the proliferation and fatty acid anabolism regulation of human pancreatic cancer cells. Methods Human pancreatic cancer cell lines AsPC-1, AsPC-1/GEM(AR), PANC-1 and MiaPaCa-2 were used as the study subjects; cell survival rate was detected by sulfonylrhodamine B(SRB); the mRNA level of key genes for fatty acid synthesis was detected by qPCR; the protein level of the AMPK/ACC pathway was detected by Western blot; intracellular lipid metabolites were examined by liquid chromatography-mass spectrometry(LC-MS). Results Comparing to control group, CTO significantly decreased the cell viability of AsPC-1, AR, PANC-1, and MiaPaCa-2(P＜0.05). CTO down-regulated the mRNA level of key fatty acid synthesis genes(P＜0.05). CTO significantly reduced the protein expression of AMPK, ACC and c-Myc(P＜0.05), while increasing the protein expression of p-AMPK and p-ACC(P＜0.05). CTO decreased lipid metabolite content in AR cells(P＜0.05). Conclusions CTO attenuates cellular fatty acid anabolism by inhibition of oncogene c-Myc expression and AMPK/ACC pathway, down-regulates the expression of fatty acid synthesis-related genes, and then inhibits proliferation of the human pancreatic cancer cell lines AsPC-1, AR, PANC-1 and MiaPaCa-2.

Key words: carboxyamidotriazole-orotate, pancreatic cancer, proliferation, fatty acid anabolism

CLC Number:

GUO Hongjiang, XU Yeting, ZHANG Diya, QIU Jiaxing, WANG Yucheng, JU Rui, GUO Lei. Effect of carboxyamidotriazole-orotate on proliferation and fatty acid anabolism of human pancreatic cancer cell lines[J]. Basic & Clinical Medicine, 2024, 44(4): 440-446.

References 14

[1]	Siegel RL, Miller KD, Wagle NS, et al. Cancer statistics, 2023[J]. CA Cancer J Clin, 2023, 73:17-48.
[2]	Rahib L, Wehner MR, Matrisian LM, et al. Estimated projection of US cancer incidence and death to 2040[J]. JAMA Netw Open, 2021, 4: e214708. doi:10.1001/jamanetworkopen.2021.4708.
[3]	Kim MP, Gallick GE. Gemcitabine resistance in pancre-atic cancer: picking the key players[J]. Clin Cancer Res, 2008, 14:1284-1285.
[4]	Ju R, Guo L, Li J, et al. Carboxyamidotriazole inhibits oxidative phosphorylation in cancer cells and exerts synergistic anti-cancer effect with glycolysis inhibition[J]. Cancer Lett, 2016, 370:232-241.
[5]	Shi J, Ju R, Gao H, et al. Targeting glutamine utilization to block tumour cells metabolic adaptation under the stress of carboxyamidotriazole-induced nutrients unavailability[J]. Acta Pharmaceutica Sinica B, 2022, 12: 759-773.
[6]	Metallo CM, Gameiro PA, Bell EL, et al. Reductive glutamine metabolism by IDH1 mediates lipogenesis under hypoxia[J]. Nature, 2011, 481:380-384.
[7]	Faubert B, Solmonson A, DeBerardinis RJ. Metabolic reprogramming and cancer progression[J]. Science, 2020, 368: eaaw5473. doi:10.1126/science.aaw5473.
[8]	Gu Z, Du Y, Zhao X, et al. Tumor microenvironment and metabolic remodeling in gemcitabine-based chemoresistance of pancreatic cancer[J]. Cancer Lett, 2021, 521:98-108.
[9]	Currie E, Schulze A, Zechner R, et al. Cellular fatty acid metabolism and cancer[J]. Cell Metab, 2013, 18:153-161.
[10]	Carracedo A, Cantley LC, Pandolfi PP. Cancer metabolism: fatty acid oxidation in the limelight[J]. Nat Rev Cancer, 2013, 13:227-232.
[11]	Gao L, Xu Z, Huang Z, et al. CPI-613 rewires lipid metabolism to enhance pancreatic cancer apoptosis via the AMPK-ACC signaling[J]. J Exp Clin Cancer Res, 2020, 39:73. doi:10.1186/s13046-020-01579-x.
[12]	Bian X, Liu R, Meng Y, et al. Lipid metabolism and cancer[J]. J Exp Med, 2021, 218: e20201606. doi:10.1084/jem.20201606.
[13]	Gouw AM, Margulis K, Liu NS, et al. The MYC oncogene cooperates with sterol-regulated element-binding protein to regulate lipogenesis essential for neoplastic growth[J]. Cell Metab, 2019, 30:556-572.
[14]	Chen J, Ding C, Chen Y, et al. ACSL4 reprograms fatty acid metabolism in hepatocellular carcinoma via c-Myc/SREBP1 pathway[J]. Cancer Lett, 2021, 502:154-165.

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