Histone Deacetylase Inhibitor SAHA as Potential Targeted Therapy Agent for Larynx Cancer Cells

Abstract

Objective: Laryngeal squamous cell carcinoma is one of the most common malignant tumors in the head and neck region. Due to the poor response to chemotherapeutics in patients and low survival rate, successful treatment of larynx cancer still remains a challenge. Therefore, the identification of novel treatment options is needed. We investigated the anticancer effects of suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, on two different laryngeal cancer cell lines RK33 and RK45. We also studied the antiproliferative action of SAHA in combination with cisplatin and defined the type of pharmacological interaction between these drugs. Materials and Methods: Viability and proliferation of larynx cancer cell lines were studied by methylthiazolyldiphenyl-tetrazolium bromide method and 5-bromo-2-deoxyuridine incorporation assay, respectively. The type of interaction between SAHA and cisplatin was determined by an isobolographic analysis. Western blotting, flow cytometry and quantitative polymerase chain reaction method were used to determine acetylation of histone H3, cell cycle progression and genes expression, respectively. Apoptosis was assessed by means of nucleosomes released to cytosol. Results: SAHA alone or in combination with cisplatin inhibited larynx cancer cells proliferation, whereas displayed relatively low toxicity against normal cells -primary cultures of human skin fibroblasts. The mixture of SAHA with cisplatin exerted additive and synergistic interaction in RK33 and RK45 cells, respectively. We showed that SAHA induced hyperacetylation of histone H3 K9, K14 and K23 and triggered apoptosis. SAHA also caused cell cycle arrest by upregulation of CDKN1A and downregulation of CCND1 encoding p21WAF1/CIP1 and cyclin D1 proteins, respectively. Conclusion: Our studies demonstrated that SAHA may be considered as a potential therapeutic agent against larynx tumors.

Synergistic Enhancement of Cancer Therapy Using HDAC Inhibitors: Opportunity for Clinical Trials

“…Pan-HDACis reduce tumor growth by inhibiting cancer cell proliferation. For instance, SAHA, combined with cisplatin, was considered as a potential treatment for larynx cancer cells due to the synergistic effect on cell proliferation inhibition (Grabarska et al, 2017). Also, SAHA and TSA was found to synergize with cisplatin in different tumor types, including cholangiocarcinoma cells, inducing cell growth inhibition (Asgar et al, 2016).…”

Superior anticancer activity is demonstrated by total extract of Curcuma longa L. as opposed to individual curcuminoids separated by centrifugal partition chromatography

“…This study was partially supported by the National Science Center, Warsaw, Poland (Project 2015/17/D/NZ7/00822) and by the Medical University of Lublin, Poland (Projects DS 440/2014 and DS 440/2016-2017.…”

HDAC Inhibition Induces PD-L1 Expression in a Novel Anaplastic Thyroid Cancer Cell Line

“…Suberoylanilide hyroxamic acid (SAHA) is a broad range HDAC inhibitor and is FDA approved for cutaneous T cell lymphoma [19]. Its anti-tumor effect was described in several cancer types and it is currently tested in numerous clinical trials both as a single agent or in combination with other anti-neoplastic drugs [20,21]. It induces cell cycle arrest and apoptosis in tumor cells and can inhibit angiogenesis and immunosuppressive interleukin production [22,23].…”