Brexpiprazole suppresses cell proliferation and de novo lipogenesis through AMPK/SREBP1 pathway in colorectal cancer.
AMPK
SREBP1
brexpiprazole
colorectal cancer
lipogenesis
Journal
Environmental toxicology
ISSN: 1522-7278
Titre abrégé: Environ Toxicol
Pays: United States
ID NLM: 100885357
Informations de publication
Date de publication:
Oct 2023
Oct 2023
Historique:
revised:
18
05
2023
received:
29
01
2023
accepted:
11
06
2023
medline:
19
9
2023
pubmed:
22
6
2023
entrez:
22
6
2023
Statut:
ppublish
Résumé
In the present study, we investigated the role of brexpiprazole on cell proliferation and lipogenesis in colorectal cancer (CRC) and its molecular mechanism. The effect of brexpiprazole on CRC cell proliferation was determined by CCK-8, EdU assay, cell clone formation. The flow cytometry was evaluated cell cycle. Differential expression genes (DEGs) were identified by RNA-seq assay after treating HCT116 cells with or without 20 μM brexpiprazole for 24 h. Then, the top 120 DEGs were analyzed by GO and KEGG enrichment analysis. After that, Oil red O staining and the levels of total cholestenone and triglyceride were measured to assess lipogenesis capacity in CRC cells. The related molecules of cell proliferation, lipogenic and AMPK/SREBP1 signal pathways were measured by q-PCR, western blot and immunohistochemical staining. Brexpiprazole remarkably suppressed cell proliferation, lipogenesis, and induced cell cycle arrest in CRC. The underlying mechanisms probably involved the suppression of SREBP1 and the stimulation of AMPK. Brexpiprazole inhibited cell proliferation and de novo lipogenesis through AMPK/SREBP1 pathway in CRC.
Substances chimiques
AMP-Activated Protein Kinases
EC 2.7.11.31
brexpiprazole
2J3YBM1K8C
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2352-2360Subventions
Organisme : Provincial key cultivation project of Science and Technology Development Plan of North Sichuan Medical College
ID : CYB22-ZDA11
Organisme : Talent Project of First Affiliated Hospital of Kunming Medical University
ID : 2022535Q02
Organisme : Strategic Cooperation Research Project of Nanchong
ID : 22SXQT0332
Informations de copyright
© 2023 Wiley Periodicals LLC.
Références
Malki A, El Ruz RA, Gupta I, Allouch A, Vranic S, Al Moustafa AE. Molecular mechanisms of colon cancer progression and metastasis: recent insights and advancements. Int J Mol Sci. 2020;22(1):130.
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2021. CA Cancer J Clin. 2021;71(1):7-33.
Kennedy RD, Bylesjo M, Kerr P, et al. Development and independent validation of a prognostic assay for stage II colon cancer using formalin-fixed paraffin-embedded tissue. J Clin Oncol. 2011;29(35):4620-4626.
Biller LH, Schrag D. Diagnosis and treatment of metastatic colorectal cancer: a review. JAMA. 2021;325(7):669-685.
Vlachos N, Lampros M, Voulgaris S, Alexiou GA. Repurposing antipsychotics for cancer treatment. Biomedicines. 2021;9:12.
Fornaro M, Fusco A, Anastasia A, Cattaneo CI, De Berardis D. Brexpiprazole for treatment-resistant major depressive disorder. Expert Opin Pharmacother. 2019;20(16):1925-1933.
Sanomachi T, Suzuki S, Togashi K, et al. Brexpiprazole reduces survivin and reverses EGFR tyrosine kinase inhibitor resistance in lung and pancreatic cancer. Anticancer Res. 2019;39(9):4817-4828.
Suzuki S, Yamamoto M, Sanomachi T, et al. Brexpiprazole, a serotonin-dopamine activity modulator, can sensitize glioma stem cells to osimertinib, a third-generation EGFR-TKI, via survivin reduction. Cancers (Basel). 2019;11(7):947.
Suzuki S, Yamamoto M, Togashi K, et al. And anti-tumor effects of brexpiprazole, a newly-developed serotonin-dopamine activity modulator with an improved safety profile. Oncotarget. 2019;10(37):3547-3558.
Ocvirk S, O'Keefe SJD. Dietary fat, bile acid metabolism and colorectal cancer. Semin Cancer Biol. 2021;73:347-355.
Mounier C, Bouraoui L, Rassart E. Lipogenesis in cancer progression (review). Int J Oncol. 2014;45(2):485-492.
Yu X-H, Ren X-H, Liang X-H, Tang YL. Roles of fatty acid metabolism in tumourigenesis: beyond providing nutrition (review). Mol Med Rep. 2018;18(6):5307-5316.
De Miguel D, Gallego-Lleyda A, Ayuso JM, et al. High-order TRAIL oligomer formation in TRAIL-coated lipid nanoparticles enhances DR5 cross-linking and increases antitumour effect against colon cancer. Cancer Lett. 2016;383(2):250-260.
Cheng C, Ru P, Geng F, et al. Glucose-mediated N-glycosylation of SCAP is essential for SREBP-1 activation and tumor growth. Cancer Cell. 2015;28(5):569-581.
Wen Y-A, Xiong X, Zaytseva YY, et al. Downregulation of SREBP inhibits tumor growth and initiation by altering cellular metabolism in colon cancer. Cell Death Dis. 2018;9(3):265.
Cool B, Zinker B, Chiou W, et al. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab. 2006;3(6):403-416.
Xie J, Wang Y, Jiang W-W, et al. Leaf petroleum ether extract inhibits lipogenesis by activating the AMPK signaling pathway. Front Pharmacol. 2018;9:1447.
Li Y, Wang Y, Li J, et al. Tacrolimus inhibits oral carcinogenesis through cell cycle control. Biomed Pharmacother. 2021;139:111545.
Röhrig F, Schulze A. The multifaceted roles of fatty acid synthesis in cancer. Nat Rev Cancer. 2016;16(11):732-749.
Horton JD, Goldstein JL, Brown MS. SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest. 2002;109(9):1125-1131.
Shao W, Espenshade PJ. Expanding roles for SREBP in metabolism. Cell Metab. 2012;16(4):414-419.
Brown MS, Goldstein JL. A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proc Natl Acad Sci USA. 1999;96(20):11041-11048.
Kotzka J, Knebel B, Avci H, et al. Phosphorylation of sterol regulatory element-binding protein (SREBP)-1a links growth hormone action to lipid metabolism in hepatocytes. Atherosclerosis. 2010;213(1):156-165.
Xu X, So J-S, Park J-G, Lee AH. Transcriptional control of hepatic lipid metabolism by SREBP and ChREBP. Semin Liver Dis. 2013;33(4):301-311.
Shi Y, Fan Y, Hu Y, et al. α-Mangostin suppresses the de novo lipogenesis and enhances the chemotherapeutic response to gemcitabine in gallbladder carcinoma cells via targeting the AMPK/SREBP1 cascades. J Cell Mol Med. 2020;24(1):760-771.
Zhu X, Bian H, Wang L, et al. Berberine attenuates nonalcoholic hepatic steatosis through the AMPK-SREBP-1c-SCD1 pathway. Free Radic Biol Med. 2019;141:192-204.
Frankel JS, Schwartz TL. Brexpiprazole and cariprazine: distinguishing two new atypical antipsychotics from the original dopamine stabilizer aripiprazole. Ther Adv Psychopharmacol. 2017;7(1):29-41.
Aladeen T, Westphal E, Lee Y, et al. The use of brexpiprazole amongst individuals with insufficient outcomes with aripiprazole or bupropion: a case series. Perspect Psychiatr Care. 2018;54(4):507-513.
Ishigooka J, Iwashita S, Tadori Y. Efficacy and safety of brexpiprazole for the treatment of acute schizophrenia in Japan: a 6-week, randomized, double-blind, placebo-controlled study. Psychiatry Clin Neurosci. 2018;72(9):692-700.
Frampton JE. Brexpiprazole: a review in schizophrenia. Drugs. 2019;79(2):189-200.
Jackowski S. Coordination of membrane phospholipid synthesis with the cell cycle. J Biol Chem. 1994;269(5):3858-3867.
Brusselmans K, De Schrijver E, Verhoeven G, et al. RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res. 2005;65(15):6719-6725.
Currie E, Schulze A, Zechner R, Walther TC, Farese RV Jr. Cellular fatty acid metabolism and cancer. Cell Metab. 2013;18(2):153-161.
Cha J-Y, Lee H-J. Targeting lipid metabolic reprogramming as anticancer therapeutics. J Cancer Prev. 2016;21(4):209-215.
Khwairakpam AD, Shyamananda MS, Sailo BL, et al. ATP citrate lyase (ACLY): a promising target for cancer prevention and treatment. Curr Drug Targets. 2015;16(2):156-163.
Chang L, Wu P, Senthilkumar R, et al. Loss of fatty acid synthase suppresses the malignant phenotype of colorectal cancer cells by down-regulating energy metabolism and mTOR signaling pathway. J Cancer Res Clin Oncol. 2016;142(1):59-72.
Wang H, Xi Q, Wu G. Fatty acid synthase regulates invasion and metastasis of colorectal cancer via Wnt signaling pathway. Cancer Med. 2016;5(7):1599-1606.
Ran H, Zhu Y, Deng R, et al. Stearoyl-CoA desaturase-1 promotes colorectal cancer metastasis in response to glucose by suppressing PTEN. J Exp Clin Cancer Res. 2018;37(1):54.
Cheng C, Geng F, Cheng X, Guo D. Lipid metabolism reprogramming and its potential targets in cancer. Cancer Commun (Lond). 2018;38(1):27.
Gao Y, Nan X, Shi X, et al. SREBP1 promotes the invasion of colorectal cancer accompanied upregulation of MMP7 expression and NF-κB pathway activation. BMC Cancer. 2019;19(1):685.
Gao Y, Zhao Q, Mu X, et al. SREBP1 promotes 5-FU resistance in colorectal cancer cells by inhibiting the expression of caspase7. Int J Clin Exp Pathol. 2019;12(3):1095-1100.
Zhao Q, Lin X, Wang G. Targeting SREBP-1-mediated lipogenesis as potential strategies for cancer. Front Oncol. 2022;12:952371.
Zhai D, Cui C, Xie L, Cai L, Yu J. Sterol regulatory element-binding protein 1 cooperates with c-Myc to promote epithelial-mesenchymal transition in colorectal cancer. Oncol Lett. 2018;15(4):5959-5965.
Lally JSV, Ghoshal S, DePeralta DK, et al. Inhibition of acetyl-CoA carboxylase by phosphorylation or the inhibitor ND-654 suppresses lipogenesis and hepatocellular carcinoma. Cell Metab. 2019;29(1):174-182.e5.
Svensson RU, Parker SJ, Eichner LJ, et al. Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models. Nat Med. 2016;22(10):1108-1119.
Hardie DG. The AMP-activated protein kinase pathway - new players upstream and downstream. J Cell Sci. 2004;117(23):5479-5487.
Li Y, Xu S, Mihaylova MM, et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice. Cell Metab. 2011;13(4):376-388.
Zhao Y, Li M, Yao X, et al. HCAR1/MCT1 regulates tumor ferroptosis through the lactate-mediated AMPK-SCD1 activity and its therapeutic implications. Cell Rep. 2020;33(10):108487.