Fatty acid synthase as a potential new therapeutic target for cervical cancer

Abstract

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 fi nding in the development of new treatment approaches for this cancer type.

Oleate Epoxides Derived from Palm Oil as New Anticancer Agents: Synthesis, Cytotoxicity Evaluation, and Molecular Docking Studies Against FASN Protein

“…On the other hand, C ‐phenylcalix[4]resorcinarene epoxide also exhibited low toxicity against Vero normal cells with a SI value of 7.32 against MCF‐7 breast cancer cells [50] . These data add a new perspective to complement the discussion in previous studies regarding the anticancer activity of monoepoxide compounds from unsaturated fatty acids [13,51–55] . Further molecular docking studies were performed to understand the cellular mechanism of epoxidized oleate compound toward FASN protein in human cancer cells…”

“…[50] These data add a new perspective to complement the discussion in previous studies regarding the anticancer activity of monoepoxide compounds from unsaturated fatty acids. [13,[51][52][53][54][55] Further molecular docking studies were performed to understand the cellular mechanism of epoxidized oleate compound toward FASN protein in human cancer cells…”

“…Cerulenin and orlistat have been reported to have strong anticancer activity through the inhibition of FASN protein in multicell cancer targets. [26,29,30,53] Molecular docking of epoxidized oleate to the thioesterase subunit of FASN has been conducted through validation with redocking to set the grid box. Redocking of orlistat as a native ligand of FASN protein (2PX6) gives an RMSD value of 1.39 Å and a binding affinity value of À 8.6 kcal/mol.…”

Immune infiltration and a necroptosis-related gene signature for predicting the prognosis of patients with cervical cancer

“…Its overexpression is often associated with tumor progression and poor prognosis (Cao et al, 2017). FASN may be a potential therapeutic target for CC, and a FASN inhibitor (orlistat) reduces apoptosis triggered by CC cells (C-33A, ME-180, HeLa, and SiHa) in a time-dependent manner (Nascimento et al, 2022). S100A10 may have anti-apoptotic effects in cancer cells, interacting with Bad and impeding its pro-apoptotic activity (Bharadwaj et al, 2021).…”

Fatty acid metabolism: A new therapeutic target for cervical cancer

“…However, in cell experiments, orlistat significantly inhibited the growth and proliferation of CC cells, and this effect was more significant in HPV16-positive and HPV18-positive CC cells. The mechanism underlying these effects was not related to necrosis but was related to apoptosis ( 32 ). One of the reasons for this result is that the sample size of this study was relatively small, and it may also be possible that FASN plays an important role in early tumor transformation.…”