Apoptosis signaling molecules as treatment targets in head and neck squamous cell carcinoma

Ow, Thomas J.; Thomas, Carlos; Fulcher, Cory D.; Chen, Jianhong; López, Andrea; Reyna, Denis E.; Prystowsky, Michael B.; Smith, Richard V.; Schiff, Bradley A.; Rosenblatt, Gregory S.; Belbin, Thomas J.; Harris, Thomas M.; Childs, Geoffrey; Kawachi, Nicole

doi:10.1002/lary.28441

Cited by 17 publications

(15 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We next investigated why could AS and/or SRP inhibit CTXinduced myelosuppression. It is well-known that the increased expression of pro-apoptotic factor Bax and the decreased expression of anti-apoptotic factor Bcl-2 can activate the cleavage of casepase3 and induce apoptosis (20). In the present study, CTX induced BHMSC apoptosis by down-regulation of Bcl-2 and upregulation of Bax, with activation of caspase3.…”

Section: Discussionsupporting

confidence: 55%

Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p

Zhu

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

Our previous study revealed that Shuanghuang Shengbai granule could cure the myelosuppression induced by cyclophosphamide (CTX) in lung cancer. However, its hematopoietic effects and molecular mechanisms remain not fully understood. Therefore, this study was intended to investigate the effects and the underlying mechanisms of Astragaloside IV (AS) and saponins of rhizoma polygonati (SRP), the two main bioactive ingredients of Shuanghuang Shengbai granule, on CTX-induced myelosuppression. CTX inhibited the proliferation and promoted apoptosis in bone marrow hematopoietic stem cells (BMHSCs), accompanied by the increased expression of miR-142-3p. AS and/or SRP treatment could alleviate CTX-induced cell injury and suppress the expression of miR-142-3p. Over-expression of miR-142-3p partially reversed the therapeutic effect of AS and/or SRP on CTX-induced cell injury in BMHSCs. Further mechanism exploration discovered that HMGB1 was the target gene of miR-142-3p, and miR-142-3p negatively regulated the expression of HMGB1. To further explore the function of AS and/or SRP in vivo, we constructed a lung cancer xenograft combined with CTX-induced myelosuppression mouse model, and we found that AS and SRP remarkably reversed the CTX-induced reduction of white blood cells, bone marrow nucleated cells, and thymus index in vivo and did not affect the chemotherapy effect of lung cancer. Collectively, our results strongly suggested that AS and SRP could improve the hematopoietic function of myelosuppressed lung cancer mice, and their effects may be related to the inhibition of miR-142-3p expression in BMHSCs.

show abstract

Section: Discussionsupporting

confidence: 55%

Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p

Zhu

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…We observed markedly increased expression of activated caspase-3 in the CTEN-knockdown cancer cell cultures compared to control siRNA-treated paired samples (median positive staining % nuclei per high power field: 5.19 (siCtrl, IQR 4.94–6.16) vs. 0.85 (siCTEN, IQR 8.46–10.14), p = 0.0027, respectively) with Western blot confirmation. Ow et al [ 41 ] found, in two independent datasets, that BCL2L1 and MCL1 are the most significantly elevated anti-apoptotic markers in HNSCC. We therefore analysed the TCGA HNSCC database for correlation between CTEN and pro-apoptotic CASP3 and anti-apoptotic BCL2L1 and MCL1 [ 42 , 43 ] ( Figure S6 ).…”

Section: Resultsmentioning

confidence: 99%

CTEN Induces Tumour Cell Invasion and Survival and Is Prognostic in Radiotherapy-Treated Head and Neck Cancer

Fleming

Woo

Moutasim

et al. 2020

Cancers

View full text Add to dashboard Cite

Head and neck squamous cell carcinoma (HNSCC) is a heterogenous disease treated with surgery and/or (chemo) radiotherapy, but up to 50% of patients with late-stage disease develop locoregional recurrence. Determining the mechanisms underpinning treatment resistance could identify new therapeutic targets and aid treatment selection. C-terminal tensin-like (CTEN) is a member of the tensin family, upregulated in several cancers, although its expression and function in HNSCC are unknown. We found that CTEN is commonly upregulated in HNSCC, particularly HPV−ve tumours. In vitro CTEN was upregulated in HPV−ve (n = 5) and HPV+ve (n = 2) HNSCC cell lines. Stable shRNA knockdown of CTEN in vivo significantly reduced tumour growth (SCC-25), and functional analyses in vitro showed that CTEN promoted tumour cell invasion, colony formation and growth in 3D-culture (SCC-25, Detroit 562). RNA sequencing of SCC-25 cells following CTEN siRNA knockdown identified 349 differentially expressed genes (logFC > 1, p < 0.05). Gene ontology analysis highlighted terms relating to cell locomotion and apoptosis, consistent with in vitro findings. A membrane-based antibody array confirmed that CTEN regulated multiple apoptosis-associated proteins, including HSP60 and cleaved caspase-3. Notably, in a mixed cohort of HPV+ve and HPV−ve HNSCC patients (n = 259), we found a significant, independent negative association of CTEN with prognosis, limited to those patients treated with (chemo)radiotherapy, not surgery, irrespective of human papillomavirus (HPV) status. These data show that CTEN is commonly upregulated in HNSCC and exerts several functional effects. Its potential role in modulating apoptotic response to therapy suggests utility as a predictive biomarker or radio-sensitising target.

show abstract

“…For head and neck tumors, bortezomib does not significantly inhibit proliferation-related pathways, such as STAT3, and has no significant effect on the expression of EGFR; therefore, it has poor efficacy in HNSCC in drug experiments and clinical applications [ 27 , 28 ]. Nevertheless, the role of PIs in the treatment of other tumors still provides new thinking for the treatment of head and neck tumors, and some studies are currently underway [ 29 – 31 ]. This study, for the first time, elucidated the effect of proteasome inhibition on the UPP and PSMB8 in laryngeal and hypopharyngeal carcinoma cells.…”

Section: Discussionmentioning

confidence: 99%

Induction and Regulation of the Immunoproteasome Subunit β5i (PSMB8) in Laryngeal and Hypopharyngeal Carcinoma Cells

Nan-xiang

Liu

et al. 2020

Med Sci Monit

View full text Add to dashboard Cite

Departmental sources Background: The ubiquitin-proteasome pathway (UPP) is closely associated with the occurrence and progression of cancer, and the 5i immunoproteasome subunit is an important antitumor target in UPP. This study aimed to characterize the regulation of the immunoproteasome subunit b5i (PSMB8) in JHU-011 laryngeal carcinoma cells and FaDu hypopharyngeal carcinoma cells to explore a new target for the treatment of laryngeal and hypopharyngeal carcinomas. Material/Methods: JHU-011 and FaDu cells were used as effector cells in this study. By means of 60 Co g-irradiation, the construction of stable cell lines of the silenced proto-oncogene c-Abl, and the addition of exogenous tyrosine kinase inhibitor (TKI) and activator, the transcription and protein expression levels of PSMB8 and its alternatively spliced isoforms in both cell lines were detected by real-time fluorescence quantitative polymerase chain reaction (RT-PCR) and Western blot. Results: Ionizing radiation upregulated the transcription level of the alternatively spliced isoform of PSMB8, E2, in both cell lines, thereby upregulating the mRNA and protein levels of PSMB8. The silencing of the proto-oncogene c-Abl and the activation and inhibition of its kinetic kinase product can affect the transcription and protein levels of PSMB8. Conclusions: Ionizing radiation can significantly upregulate the mRNA and protein levels of PSMB8, which happens through the upregulation of its splicing isoform E2. The proto-oncogene c-Abl and its kinetic kinase protein product can regulate the transcription and protein expression levels of PSMB8 and its alternatively spliced isoforms.

show abstract

Apoptosis signaling molecules as treatment targets in head and neck squamous cell carcinoma

Cited by 17 publications

References 36 publications

Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p

Astragaloside IV and Saponins of Rhizoma Polygonati Cure Cyclophosphamide-Induced Myelosuppression in Lung Adenocarcinoma via Down-Regulating miR-142-3p

CTEN Induces Tumour Cell Invasion and Survival and Is Prognostic in Radiotherapy-Treated Head and Neck Cancer

Induction and Regulation of the Immunoproteasome Subunit β5i (PSMB8) in Laryngeal and Hypopharyngeal Carcinoma Cells

Contact Info

Product

Resources

About