Bacterial Antigens Reduced the Inhibition Effect of Capsaicin on Cal 27 Oral Cancer Cell Proliferation.

Rajdeep Chakraborty,Charbel Darido,Shoba Ranganathan,Honghua Hu,Karen Vickery

doi:10.3390/ijms22168686

Abstract

Oral cancer is a major global health problem with high incidence and low survival rates. The oral cavity contains biofilms as dental plaques that harbour both Gram-negative and Gram-positive bacterial antigens, lipopolysaccharide (LPS) and lipoteichoic acid (LTA), respectively. LPS and LTA are known to stimulate cancer cell growth, and the bioactive phytochemical capsaicin has been reported to reverse this effect. Here, we tested the efficacy of oral cancer chemotherapy treatment with capsaicin in the presence of LPS, LTA or the combination of both antigens. LPS and LTA were administered to Cal 27 oral cancer cells prior to and/or concurrently with capsaicin, and the treatment efficacy was evaluated by measuring cell proliferation and apoptotic cell death. We found that while capsaicin inhibits oral cancer cell proliferation and metabolism (MT Glo assay) and increases cell death (Trypan blue exclusion assay and Caspase 3/7 expression), its anti-cancer effect was significantly reduced on cells that are either primed or exposed to the bacterial antigens. Capsaicin treatment significantly increased oral cancer cells’ suppressor of cytokine signalling 3 gene expression. This increase was reversed in the presence of bacterial antigens during treatment. Our data establish a rationale for clinical consideration of bacterial antigens that may interfere with the treatment efficacy of oral cancer.

Highlights

Published: 12 August 2021Oral squamous cell carcinoma (OSCC) is a major global health problem with high incidence and low survival rates
Chronic bacterial infections have been shown to be associated with chronic inflammation, anti-apoptotic activity and pro-proliferative activities, and the Gram-negative, anaerobic bacteria, Porphyromonas gingivalis and Fusobacterium nucleatum contribute to oral carcinogenesis and progression of oral cancer [1]
Titration of capsaicin found that theand maximum relevant concentration that of capsaicin found that thenormal maximum relevant concentration that could beTitration used without adversely affecting cells clinically was 150 μM

Summary

Introduction

Published: 12 August 2021Oral squamous cell carcinoma (OSCC) is a major global health problem with high incidence and low survival rates. Chronic bacterial infections have been shown to be associated with chronic inflammation, anti-apoptotic activity and pro-proliferative activities, and the Gram-negative, anaerobic bacteria, Porphyromonas gingivalis and Fusobacterium nucleatum contribute to oral carcinogenesis and progression of oral cancer [1]. Oral colonisers include Gram-positive bacterial species from the Streptococcus and Actinomyces families which produce lipoteichoic acid (LTA). Late oral colonisers include Gram-negative bacterial species F. nucleatum, P. gingivalis and Prevotella spp., which produce lipopolysaccharide (LPS). Both Gram-positive and Gram-negative bacteria form oral biofilms. Bacterial infection has been shown to be associated with chronic inflammation, anti-apoptotic activity, pro-proliferative activities, which play a role in cancer development [2]

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