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Apoptosis signaling molecules as treatment targets in head and neck squamous cell carcinoma
Author(s) -
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,
Belbin Thomas J.,
Harris Thomas M.,
Childs Geoffrey C.,
Kawachi Nicole,
Schlecht Nicolas F.,
Gavathiotis Evripidis
Publication year - 2020
Publication title -
the laryngoscope
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.181
H-Index - 148
eISSN - 1531-4995
pISSN - 0023-852X
DOI - 10.1002/lary.28441
Subject(s) - mcl1 , head and neck squamous cell carcinoma , apoptosis , bortezomib , cancer research , cell , cell culture , annexin a5 , biology , annexin , programmed cell death , cancer , head and neck cancer , medicine , downregulation and upregulation , immunology , multiple myeloma , gene , genetics
Objectives To evaluate BCL‐2 family signaling molecules in head and neck squamous cell carcinoma (HNSCC) and examine the ability of therapeutic agents with variable mechanisms of action to induce apoptosis in HNSCC cells. Methods messenger ribonculeic acid (mRNA) expression of BAK, BAX, B‐cell lymphoma (Bcl‐2), BCL2 Like 1 (BCL2L1), and MCL1 were measured in The Cancer Genome Atlas (TCGA) head and neck cancer dataset, as well as in a dataset from a cohort at Montefiore Medical Center (MMC). Protein expression was similarly evaluated in a panel of HNSCC cell lines (HN30, HN31, HN5, MDA686LN, UMSCC47). Cell viability and Annexin V assays were used to assess the efficacy and apoptotic potential of a variety of agents (ABT‐263 [navitoclax], A‐1210477, and bortezomib. Results Expression of BAK, BAX, BCL2L1, and MCL1 were each significantly higher than expression of BCL2 in the TCGA and MMC datasets. Protein expression demonstrated the same pattern of expression when examined in HNSCC cell lines. Treatment with combined ABT‐263 (navitoclax)/A‐1210477 or with bortezomib demonstrated apoptosis responses that approached or exceeded treatment with staurospaurine control. Conclusion HNSCC cells rely on inhibition of apoptosis via BCL‐xL and MCL‐1 overexpression, and induction of apoptosis remains a potential therapeutic option as long as strategies overcome redundant anti‐apoptotic signals. Level of Evidence NA Laryngoscope , 130:2643–2649, 2020