BX795, a TBK1 inhibitor, exhibits antitumor activity in human oral squamous cell carcinoma through apoptosis induction and mitotic phase arrest. | LitMetric
Department of Biological Science and Technology, China Medical University, Taichung 40447, Taiwan. Electronic address:
Published: December 2015
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Article Abstract
TANK-binding kinase 1 (TBK1), a member of IκB Kinase (IKK)-related kinases, plays a role in regulating innate immunity, inflammation and oncogenic signaling. This study aims to investigate the role of BX795, an inhibitor of TBK1, in a panel of oral squamous cell carcinoma (OSCC) cell lines. The antitumor effects and mechanisms of BX795 were assessed by MTT assays, flow cytometry, Western blotting, and confocal microscopy. BX795 exhibited a dose-responsive antiproliferative effect on OSCC cells with relative sparing of normal human oral keratinocytes. The compound caused apoptosis as evidenced by PARP cleavage, the presence of pyknotic nuclei in the TUNEL assay, and fragmented DNA tails in the Comet assay. BX795 inhibits Akt and NF-κB signaling, arrests cells in the mitotic phase, and increases generation of autophagy in oral cancer cells. Interestingly, the antiproliferative activity of BX795 does not correlate with TBK1 protein expression level in OSCC cells. We propose that the TBK1-independet effect is related to mitotic phase arrest. Pleiotropic anticancer activity with relative sparing of normal oral keratinocytes underscores the potential value of BX795 and warrants its further study in oral squamous cell carcinoma therapy.
Clinical Genetics Lab, Centre for Cellular and Molecular Research, Saveetha Dental College & Hospital, Saveetha Institute of Medical and Technical Sciences [SIMATS], Saveetha University, Chennai, India.
Background: Periodontitis is considered to be one of the major risk factors associated with cancers of the oral cavity. Periodontogenic pathogens such as and are the important pathogens associated with periodontitis. Chronic exposure to bacterial components induces changes in the nearby cells.
Squamous carcinoma of the head and neck is characterized by aberrant apoptosis that prolongs the proliferative capacity of the cells and by uncontrolled cell growth. This study aimed to examine the pro-apoptotic and antiproliferative effects of cassane diterpenoids on squamous carcinoma cells . The cytotoxicity of four (4) cassane diterpenoids {Six-cinnamoyl- 7-hydroxyvouacapen-5-ol(1), pulcherrimin A(2), C(3), and E(4)} isolated from C.
Actinomycosis is an infection caused by and mainly affects cervicofacial areas. In women, other regions, such as the chest, abdomen, and pelvic cavity can involve actinomycosis. Actinomycosis lesions in the oral cavity can cause pain, swelling, induration, pus discharge, and discomfort similar to other benign or malignant pathologies.
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Aim: The hypoxic tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) is primarily regulated by hypoxia-inducible factor-1 alpha (HIF-1α), impacting histone acetylation and methylation, which contribute to drug resistance. Vorinostat, a histone deacetylase inhibitor (HDACi), de-stabilizes HIF-1α, while PX-12, a thioredoxin-1 (Trx-1) inhibitor, prevents HIF-1α accumulation. Combining HDACi with a Trx-1 inhibitor may enhance efficacy and reduce resistance by increasing reactive oxygen species (ROS) in cancer cells.
Technical Institute of Physics and Chemistry, University of Chinese Academy of Sciences, Beijing 100190, China; Hangzhou CASbios Medical Co., Hangzhou 310000, China. Electronic address:
Oral squamous cell carcinoma (OSCC) is one of the most prevalent malignant tumors in the oral and maxillofacial region. Traditional treatments for OSCC, including surgery, radiotherapy, and chemotherapy, often lead to severe adverse effects. Therefore, the development of safe and effective novel cancer therapies is crucial for achieving synergistic cancer treatment, significantly enhancing patient survival and quality of life.
