Ewa Sokolowska1, Malgorzata Presler2, Elzbieta Goyke2, Ryszard Milczarek1, Julian Swierczynski2,3, Tomasz Sledzinski4. 1. Department of Pharmaceutical Biochemistry, Medical University of Gdansk, Gdansk, Poland. 2. Department of Biochemistry, Medical University of Gdansk, Gdansk, Poland. 3. State School of Higher Vocational Education in Koszalin, Koszalin, Poland. 4. Department of Pharmaceutical Biochemistry, Medical University of Gdansk, Gdansk, Poland tsledz@gumed.edu.pl.
Abstract
BACKGROUND/AIM: Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating human pancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation. MATERIALS AND METHODS: The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture. RESULTS: Expression of FASN increased during proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant reduction of PANC-1 proliferation and enhanced apoptosis of these cells. CONCLUSION: This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer. Copyright
BACKGROUND/AIM: Pancreatic cancer is a disease with very poor prognosis, and none of currently available pharmacotherapies have proven to be efficient in this indication. The aim of this study was to analyze the expression of fatty acid synthase (FASN) gene as a potential therapeutic target in proliferating humanpancreatic cancer cells (PANC-1), and verify if orlistat, originally developed as an anti-obesity drug, inhibits PANC-1 proliferation. MATERIALS AND METHODS: The effects of orlistat on gene expression, lipogenesis, proliferation and apoptosis was studied in PANC-1 cell culture. RESULTS: Expression of FASN increased during proliferation of PANC-1. Inhibition of FASN by orlistat resulted in a significant reduction of PANC-1 proliferation and enhanced apoptosis of these cells. CONCLUSION: This study showed, to our knowledge for the first time, that orlistat exhibits significant antitumor activity against PANC-1 cells. This implies that orlistat analogs with good oral bioavailability may find application in pharmacotherapy of pancreatic cancer. Copyright
Authors: Wenjing Zhou; Jing Zhang; Mingkun Yan; Jin Wu; Shuo Lian; Kang Sun; Baiqing Li; Jia Ma; Jun Xia; Chaoqun Lian Journal: Front Med Date: 2021-06-04 Impact factor: 4.592
Authors: Advait Shetty; Prashanth K B Nagesh; Saini Setua; Bilal B Hafeez; Meena Jaggi; Murali M Yallapu; Subhash C Chauhan Journal: ACS Omega Date: 2020-04-13