Fatty acid synthase as a potential new therapeutic target for cervical cancer.
Jéssica NascimentoCamila MariotDébora Renz Barreto ViannaLúcia M KliemannPaula S ChavesMassimo LodaAndreia BuffonRuy Carlos Ruver BeckDiogo André PilgerPublished in: Anais da Academia Brasileira de Ciencias (2022)
Fatty acid synthase (FASN) is the rate-limiting enzyme for the de novo synthesis of fatty acids in the cytoplasm of tumour cells. Many tumour cells express high levels of FASN, and its expression is associated with a poorer prognosis. Cervical cancer is a major public health problem, representing the fourth most common cancer affecting women worldwide. To date, only a few in silico studies have correlated FASN expression with cervical cancer. This study aimed to investigate in vitro FASN expression in premalignant lesions and cervical cancer samples and the effects of a FASN inhibitor on cervical cancer cells. FASN expression was observed in all cervical cancer samples with increased expression at more advanced cervical cancer stages. The FASN inhibitor (orlistat) reduced the in vitro cell viability of cervical cancer cells (C-33A, ME-180, HeLa and SiHa) in a time-dependent manner and triggered apoptosis. FASN inhibitor also led to cell cycle arrest and autophagy. FASN may be a potential therapeutic target for cervical cancer, and medicinal chemists, pharmaceutical researchers and formulators should consider this finding in the development of new treatment approaches for this cancer type.
Keyphrases
- cell cycle arrest
- poor prognosis
- fatty acid
- cell death
- public health
- pi k akt
- induced apoptosis
- endoplasmic reticulum stress
- binding protein
- oxidative stress
- long non coding rna
- type diabetes
- papillary thyroid
- squamous cell carcinoma
- pregnant women
- metabolic syndrome
- molecular docking
- polycystic ovary syndrome
- climate change
- adipose tissue
- insulin resistance
- molecular dynamics simulations
- global health
- combination therapy
- pregnancy outcomes
- smoking cessation