scholarly journals ML218 HCl Is More Efficient Than Capsaicin in Inhibiting Bacterial Antigen-Induced Cal 27 Oral Cancer Cell Proliferation

2021 ◽  
Vol 22 (22) ◽  
pp. 12559
Author(s):  
Rajdeep Chakraborty ◽  
Honghua Hu ◽  
Charbel Darido ◽  
Karen Vickery ◽  
Shoba Ranganathan

The bacterial antigen, lipopolysaccharide (LPS) and disruptions in calcium channels are independently known to influence oral cancer progression. Previously, we found that bacterial antigens, LPS and lipoteichoic acid (LTA) act as confounders during the action of capsaicin on Cal 27 oral cancer proliferation. As calcium channel drugs may affect oral cancer cell proliferation, we investigated the effect of ML218 HCl, a T-type voltage-gated calcium channel blocker, on the proliferation of Cal 27 oral cancer cells. We hypothesized that ML218 HCl could effectively reduce LPS-induced oral cancer cell proliferation. LPS and LTA antigens were added to Cal 27 oral cancer cells either prior to and/or concurrently with ML218 HCl treatment, and the efficacy of the treatment was evaluated by measuring Cal 27 proliferation, cell death and apoptosis. ML218 HCl inhibited oral cancer cell proliferation, increased apoptosis and cell death, but their efficacy was significantly reduced in the presence of bacterial antigens. ML218 HCl proved more effective than capsaicin in reducing bacterial antigen-induced Cal 27 oral cancer cell proliferation. Our results also suggest an interplay of proliferation factors during the bacterial antigens and calcium channel drug interaction in Cal 27. Bacterial antigen reduction of drug efficacy should be considered for developing newer pharmacological agents or testing the efficacy of the existing oral cancer chemotherapeutic agents. Finally, voltage gated calcium channel drugs should be considered for future oral cancer research.

2021 ◽  
Vol 22 (16) ◽  
pp. 8686
Author(s):  
Rajdeep Chakraborty ◽  
Karen Vickery ◽  
Charbel Darido ◽  
Shoba Ranganathan ◽  
Honghua Hu

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.


2016 ◽  
Vol 21 (1) ◽  
pp. 419-427 ◽  
Author(s):  
Cheng-Yu Yang ◽  
Chih-Kung Lin ◽  
Gu-Jiun Lin ◽  
Cheng-Chih Hsieh ◽  
Shing-Hwa Huang ◽  
...  

2015 ◽  
Vol 32 (1) ◽  
pp. 62-69 ◽  
Author(s):  
Kuan-Ho Lin ◽  
Marthandam Asokan Shibu ◽  
Yueh-Hsiung Kuo ◽  
Yueh-Chiu Chen ◽  
Hsi-Hsien Hsu ◽  
...  

Author(s):  
Shoba Ranganathan ◽  
Rajdeep Chakraborty ◽  
Honghua Hu ◽  
Abubakar Siddiq Mangani ◽  
Karen Vickery ◽  
...  

Oral biofilms harbour gram-negative bacterial antigen lipopolysaccharide (LPS) involved in oral cancer progression and gram-positive bacterial surface-associated adhesive, lipoteichoic acid (LTA). Thus, we hypothesised that LPS and LTA together would increase the proliferation of cancer cells compared to stimulation by LPS alone. Oral cancer cell lines SCC4, SCC9, SCC25, Cal 27 and the normal oral cell line, OKF6, were studied. The bacterial antigen stimulation indices were determined using the MT Glo assay. Cell proliferation after bacterial antigen stimulation was validated by clonogenic assays. Phosphokinase array, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blot were employed to study proliferative and apoptotic pathways in bacterial antigen-stimulated cells. Bacterial antigens significantly stimulated Cal 27 (p ≤ 0.001) alone. SCC4 and SCC9 showed negligible stimulation with either antigen, while SCC25 results were comparable to OKF6. The combined antigen stimulation of Cal 27 led to a decrease in phosphorylated p53 and β-catenin and higher PI3K compared to LPS only stimulated cells (p ≤ 0.001). Combined bacterial antigen stimulation results in increased proliferation of Cal 27 cells due to lowering of tumor suppressor proteins and increased tumor proliferation-related proteins.


Sign in / Sign up

Export Citation Format

Share Document