Preclinical assessment of histone deacetylase inhibitor quisinostat as a therapeutic agent against esophageal squamous cell carcinoma.

Investigational New Drugs
Lei ZhongQian Peng

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most serious life-threatening malignancies. Although chemotherapeutic targets and agents for ESCC have made much progress recently, the efficacy is still unsatisfactory. Therefore, there is still an unmet medical need for patients with ESCC. Here, we report the expression status of HDAC1 in human ESCC and matched paracancerous tissues, and the results indicated that HDAC1 was generally upregulated in ESCC specimens. Furthermore, we comprehensively assessed the anti-ESCC activity of a highly active HDAC1 inhibitor quisinostat. Quisinostat could effectively suppress cellular viability and proliferation of ESCC cells, as well as induce cell cycle arrest and apoptosis even at low treatment concentrations. The effectiveness was also observed in KYSE150 xenograft model when quisinostat was administered at tolerated doses (3 mg/kg and 10 mg/kg). Meanwhile, quisinostat also had the ability to suppress the migration and invasion (pivotal steps of tumor metastasis) of ESCC cells. Western blot analysis indicated that quisinostat exerted its anti-ESCC effects mainly through blockade of Akt/mTOR and MAPK/ERK signaling cascades. Overall, HDAC1 may serve as a potential therapeutic target...Continue Reading

References

Oct 29, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Janine ArtsPatrick Angibaud
Nov 13, 2012·Molecular Oncology·Maria NewNicholas B La Thangue
May 3, 2014·International Journal of Cancer. Journal International Du Cancer·Lei ZhongSheng-Yong Yang
Aug 6, 2014·Proteomics. Clinical Applications·Lorenzo ColarossiClaudius Mueller
Feb 6, 2015·CA: a Cancer Journal for Clinicians·Lindsey A TorreAhmedin Jemal
Feb 13, 2016·Chonnam Medical Journal·Somy Yoon, Gwang Hyeon Eom
Mar 24, 2016·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Kristy WahaibPatrick D Ford
Oct 22, 2016·Pharmacogenomics·Andrew Kl GoeyWilliam D Figg
Dec 31, 2016·Expert Opinion on Therapeutic Patents·Hai-Tao QinFeng Liu
Jun 4, 2017·Surgical Oncology Clinics of North America·Talha ShaikhEric M Horwitz
Jul 4, 2017·International Journal of Molecular Sciences·Tomas EckschlagerJan Hrabeta
Mar 15, 2018·The International Journal of Biochemistry & Cell Biology·Mariarosaria ConteLucia Altucci
Apr 19, 2018·Annals of Translational Medicine·Po-Kuei Hsu
Jun 5, 2018·Trends in Cancer·Carolina Vicente-DueñasIsidro Sánchez-García

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cell Migration in Cancer and Metastasis

Migration of cancer cells into surrounding tissue and the vasculature is an initial step in tumor metastasis. Discover the latest research on cell migration in cancer and metastasis here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.

Apoptosis in Cancer

Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.

Carcinoma, Squamous Cell

Basal cell carcinoma is a form of malignant skin cancer found on the head and neck regions and has low rates of metastasis. Discover the latest research on basal cell carcinoma here.