Autophagy blockade sensitizes human head and neck squamous cell carcinoma towards CYT997 through enhancing excessively high reactive oxygen species-induced apoptosis

Homeobox C6 (HOXC6) genes belong to the homeoprotein family of transcription factors, which play an important role in morphogenesis and cellular differentiation during embryonic development. The aim of this study was to explore the role of HOXC6 in the regulation of Bcl-2 in human head and neck squamous cell carcinoma (HNSCC). The HOXC6 and Bcl-2 gene were identified as being overexpressed in HNSCC tissue and cell lines. Transfection assays demonstrated that HOXC6 increased the levels of Bcl-2 mRNA and protein. A luciferase reporter assay suggested that HOXC6 induced activity of the Bcl-2 promoter. A series of Bcl-2 promoter deletion mutants were examined and the minimal HOXC6-responsive region was identified to be in the TAAT motif (-420 bp) of the Bcl-2 promoter. Interestingly, the inhibition of HOXC6 using siRNA led to the repression of Bcl-2 expression and induced caspase-3-dependent apoptosis; overexpression of HOXC6 in HNSCC cells increased the resistance to paclitaxel-induced apoptosis. Together, our findings suggest that HOXC6 is an important mechanism of the anti-apoptotic pathway via regulation of Bcl-2 expression.

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Tailored theranostic nanoparticles cause efficient ferroptosis in head and neck squamous cell carcinoma through a reactive oxygen species “butterfly effect”

Chemical Engineering Journal ◽

10.1016/j.cej.2021.130083 ◽

2021 ◽

pp. 130083

Author(s):

Xiangkai Zhang ◽

Shengbing Yang ◽

Qing Wang ◽

Weimin Ye ◽

Shuli Liu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Reactive Oxygen ◽

Neck Squamous Cell Carcinoma ◽

Oxygen Species ◽

Theranostic Nanoparticles ◽

Butterfly Effect

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Role of JNK activation in paclitaxel‑induced apoptosis in human head and neck squamous cell carcinoma

Oncology Letters ◽

10.3892/ol.2021.12966 ◽

2021 ◽

Vol 22 (4) ◽

Author(s):

Yu-Yan Lan ◽

Ying-Hui Chen ◽

Cheng Liu ◽

Kuo-Lung Tung ◽

Yen-Ting Wu ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Human Head ◽

Neck Squamous Cell Carcinoma ◽

Induced Apoptosis ◽

Jnk Activation

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Proteasome Inhibitor PS-341 Induces Apoptosis through Induction of Endoplasmic Reticulum Stress-Reactive Oxygen Species in Head and Neck Squamous Cell Carcinoma Cells

Molecular and Cellular Biology ◽

10.1128/mcb.24.22.9695-9704.2004 ◽

2004 ◽

Vol 24 (22) ◽

pp. 9695-9704 ◽

Cited By ~ 287

Author(s):

Andrew Fribley ◽

Qinghua Zeng ◽

Cun-Yu Wang

Keyword(s):

Reactive Oxygen Species ◽

Squamous Cell Carcinoma ◽

Endoplasmic Reticulum ◽

Er Stress ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Reactive Oxygen ◽

Neck Squamous Cell Carcinoma ◽

Oxygen Species

ABSTRACT PS-341, also known as Velcade or Bortezomib, represents a new class of anticancer drugs which has been shown to potently inhibit the growth and/or progression of human cancers, including head and neck squamous cell carcinoma (HNSCC). Although it has been logically hypothesized that NF-κB is a major target of PS-341, the underlying mechanism by which PS-341 inhibits tumor cell growth is unclear. Here we found that PS-341 potently activated the caspase cascade and induced apoptosis in human HNSCC cell lines. Although PS-341 could inhibit NF-κB activation, the inhibition of NF-κB was not sufficient to initiate apoptosis in HNSCC cells. Using biochemical and microarray approaches, we found that proteasome inhibition by PS-341 induced endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) in HNSCC cells. The inhibition of ROS significantly suppressed caspase activation and apoptosis induced by PS-341. Consistently, PS-341 could not induce the ER stress-ROS in PS-341-resistant HNSCC cells. Taken together, our results suggest that in addition to the abolishment of the prosurvival NF-κB, PS-341 might directly induce apoptosis by activating proapoptotic ER stress-ROS signaling cascades in HNSCC cells, providing novel insights into the PS-341-mediated antitumor activity.

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