Resveratrol, a novel inhibitor of fatty acid binding protein 5, inhibits cervical cancer metastasis by suppressing fatty acid transport into nucleus and downstream pathways

Abstract

Background and PurposeBecause of cervical cancer (CC) metastasis, the prognosis of diagnosed patients is poor. However, the molecular mechanism of and therapeutic approach for metastatic CC remain elusive.Experimental approachIn this study, we first evaluated the effect of resveratrol (RSV) on CC cell migration and metastasis. Via an activity‐based protein profiling (ABPP) approach, a photoaffinity probe of RSV (RSV‐P) was synthesized, and the protein targets of RSV in HeLa cells were identified. Based on target information and subsequent in vivo and in vitro validation experiments, we finally elucidated the mechanism of RSV corresponding to its antimetastatic activity.Key ResultsThe results showed that RSV concentration‐dependently suppressed CC cell migration and metastasis. A list of proteins was identified as the targets of RSV through the ABPP approach with RSV‐P, among which FABP5 attracted our attention based on TCGA database analysis. Subsequent knockout and overexpression experiments confirmed that RSV directly interacted with FABP5 to inhibit fatty acid transport into the nucleus, thereby suppressing downstream MMP2 and MMP9 expression thus inhibiting CC metastasis.Conclusions and ImplicationsOur study confirmed the key role of FABP5 in CC metastasis and provided important target information for the design of therapeutic lead compounds for metastatic CC.

Advances in the role of resveratrol and its mechanism of action in common gynecological tumors

“… Jeong et al (2013) showed that RES attenuates lysophosphatidic acid-induced OC invasion by inhibiting epidermal growth factor receptor activation. According to Chen et al (2023) , RES effectively curtails the migration and metastasis of CC cells and improves survival rates in murine models. Specifically, by directly binding to fatty acid binding protein 5 (FABP5), RES competitively inhibits fatty acid binding to FABP5, consequently inhibiting MMP-2 and MMP-9 expression.…”