Exploring Anticancer Activity of Ginger-Derived Phytochemical in Regulation of NLRP3 Inflammasome in Oral Cancer

*Corresponding author: (e-mail: [e-mail]).

Abstract

Background: Oral cancer (OC) is the second most common cancer in India. It has been shown that one of the central mechanisms leading to tumor promoting inflammation is mediated by NLRP3 inflammasome pathway. Ginger (Zingiber officinale) has been used since time immemorial to treat inflammatory disorders in ayurvedic and Chinese medicine.

Methods: Expression of NLRP3 inflammasome pathway in OC tissues was determined by immunohistochemistry. Anticancer effect of 6-Shogaol on OC cell lines (AW13516 and CV60821) was assessed by SRB assay. Anti-inflammatory activity of 6-Shogaol was assessed using an inflammasome model in OC cell lines by RT-PCR and flow cytometry.

Results: It was interesting to note that 6-Shogaol had a dose-dependent growth inhibitory effect on OC cell lines. Cell cycle analysis shows that 6-Shogaol causes apoptosis in OC cell lines. Activation of in vitro inflammasome in OC cell lines led to increased expression of NLRP3 and IL-18 along with puncta formation which got reduced significantly upon 6-Shogaol treatment. Paraffin sections of human OC tissues exhibited increased expression of NLRP3 pathway markers compared to adjacent normal tissue, corroborated by our results from OC cell lines. There was increase in cytotoxicity of PBLs and TILs of patients when treated with 6-Shogaol.

Conclusion: Our study demonstrated that the NLRP3 pathway is significantly upregulated in human OC tissues/cells. 6-Shogaol successfully regulated inflammation based on NLRP3- mediated immune signaling and could be explored as immunomodulatory agent in oral cancer therapeutics.

 

MissingLinkText

Die Autoren geben an, dass kein Interessenkonflikt besteht.

Publikationsverlauf

Artikel online veröffentlicht:
08. Juli 2024