Zerumbone suppress MMP۱۳-inducedcell migration and invasion via inhibiting the FAK/ RhoA/ROCK pathway in human colorectal cancer cells

Introduction: Zerumbone (ZER) is an herbal agent that hasbeen extensively studied in treatment of a wide range of tumors.However, the details of its action on invasion and metastasis ofCRC have not been entirely investigated. Here we explored themolecular mechanism of ZER’s effect on migration and invasionof the human CRC cell lines. ZER effectively inhibitedcell migration, invasion, and growth in vitro.We found that itimpeded transcription of MMP۱۳ through modulating FAK/RhoA/ROCK. ZER suppressed focal adhesion kinase (FAK)phosphorylation and reduced expression of MMP۱۳.Materials and Methods: HCT۱۱۶ and SW۴۸ cells were treatedwith various concentrations of zerumbone. The anti proliferativeeffect of zerumbone in a time and dose dependent wasassessed by MTT and Apoptosis assays. The expression levelof FAK, RhoA and MMP۱۳ genes in a dose and time dependentmanner was determined by quantitative Real Time PCR. Theactivity of MMP۱۳ enzyme was performed using MMP activityassay kit. In addition, the activity of FAK and Rho were investigatedby western blotting assay. The invasion of HCT۱۱۶ andSW۴۸ cells was performed by invasion assay.Results: Zerumbone could significantly inhibit proliferation ofHCT۱۱۶ and SW۴۸ cell lines compared with respective untreatedcontrols. Zerumbone reduced FAK, RhoA and MMP۱۳ geneexpression compared with untreated control cells. The activityof FAK, RhoA and MMP-۱۳ were decreased after treating withZerumbone .The invasive abilities of HCT-۱۱۶ and SW۴۸ cellswere meaningfully reduced by Zerumbone.Therefore it can besuggested that the Zerumbone, as a herbal substance with aninhibitory potential for migration and invasion of cancer cells,may be useful in controlling the progression of this type of canceralong with chemotherapy drugs.

کلیدواژه ها:

Zerumbone ، colorectal cancer ، invasion and metastasis ، FAK