PMID- 33538066 OWN - NLM STAT- MEDLINE DCOM- 20220216 LR - 20220216 IS - 1470-8744 (Electronic) IS - 0885-4513 (Linking) VI - 69 IP - 1 DP - 2022 Feb TI - Palbociclib negatively regulates fatty acid synthesis due to upregulation of AMPKalpha and miR-33a levels to increase apoptosis in Panc-1 and MiaPaCa-2 cells. PG - 342-354 LID - 10.1002/bab.2113 [doi] AB - Fatty acids (FAs) synthesis mechanism has various regulators such as fatty acid synthase (FASN), AMP-regulated protein kinase (AMPK), or mammalian target of rapamycin (mTOR), which are aberrantly dysregulated in various pancreatic cancer cells. In this study, we aim to understand the regulatory role of palbociclib, a CDK4/6 inhibitor, on the cellular energy metabolism through regulation of AMPK/mTOR signaling by modulation of intracellular miR-33a levels in Panc-1 and MiaPaCa-2 cells. Palbociclib downregulated FAs metabolism more effectively in MiaPaCa-2 cells than Panc-1 cells. Moreover, palbociclib treatment increased the levels of miR-33a in each cell line albeit a higher increase was evident in MiaPaCa-2 cells. Stress-mediated activation of mTOR signaling axis was found associated with palbociclib-mediated AMPKalpha activation and miR33a upregulation. These findings provided that a deeper understanding about possible interactions of cell cycle activity and reduction of FAs synthesis may facilitate the enhancement of cell death mechanisms in pancreatic cancer cells. CI - (c) 2021 International Union of Biochemistry and Molecular Biology, Inc. FAU - Rencuzogullari, Ozge AU - Rencuzogullari O AUID- ORCID: 0000-0002-2157-1289 AD - Department of Molecular Biology and Genetics, Science and Literature Faculty, Istanbul Kultur University, Istanbul, Turkey. AD - Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey. FAU - Yerlikaya, Pinar Obakan AU - Yerlikaya PO AUID- ORCID: 0000-0001-7058-955X AD - Department of Molecular Biology and Genetics, Science and Literature Faculty, Istanbul Kultur University, Istanbul, Turkey. FAU - Gurkan, Ajda Coker AU - Gurkan AC AUID- ORCID: 0000-0003-2298-5755 AD - Department of Molecular Biology and Genetics, Science and Literature Faculty, Istanbul Kultur University, Istanbul, Turkey. FAU - Arisan, Elif Damla AU - Arisan ED AUID- ORCID: 0000-0002-4844-6381 AD - Department of Biotechnology, Institute of Biotechnology, Gebze Technical University, Gebze, Kocaeli, Turkey. FAU - Telci, Dilek AU - Telci D AUID- ORCID: 0000-0002-2793-6533 AD - Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey. LA - eng GR - 000x/Istanbul Kultur University Scientific Research Center/ GR - 119Z158/Turkiye Bilimsel ve Teknolojik Arastirma Kurumu/ GR - 118Z100/Turkiye Bilimsel ve Teknolojik Arastirma Kurumu/ PT - Journal Article DEP - 20210218 PL - United States TA - Biotechnol Appl Biochem JT - Biotechnology and applied biochemistry JID - 8609465 RN - 0 (Fatty Acids) RN - 0 (MicroRNAs) RN - 0 (Piperazines) RN - 0 (Pyridines) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) RN - G9ZF61LE7G (palbociclib) SB - IM MH - *AMP-Activated Protein Kinases/metabolism MH - Apoptosis MH - Cell Line, Tumor MH - Cell Proliferation MH - Fatty Acids MH - *MicroRNAs/genetics MH - Piperazines MH - Pyridines MH - Up-Regulation OTO - NOTNLM OT - AMPKalpha OT - fatty acid synthesis OT - leptin OT - miR-33a OT - palbociclib OT - pancreatic cancer EDAT- 2021/02/05 06:00 MHDA- 2022/02/17 06:00 CRDT- 2021/02/04 05:57 PHST- 2020/07/21 00:00 [received] PHST- 2021/01/10 00:00 [accepted] PHST- 2021/02/05 06:00 [pubmed] PHST- 2022/02/17 06:00 [medline] PHST- 2021/02/04 05:57 [entrez] AID - 10.1002/bab.2113 [doi] PST - ppublish SO - Biotechnol Appl Biochem. 2022 Feb;69(1):342-354. doi: 10.1002/bab.2113. Epub 2021 Feb 18.