Nikolaos Garmpis1, Christos Damaskos2,3, Anna Garmpi4, Dimitrios Dimitroulis2, Eleftherios Spartalis3, Georgios-Antonios Margonis5, Dimitrios Schizas6, Irini Deskou6, Chrysoula Doula7, Eleni Magkouti8, Nikolaos Andreatos5, Efstathios A Antoniou2, Afroditi Nonni9, Konstantinos Kontzoglou2, Dimitrios Mantas2. 1. Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece nikosg22@hotmail.com. 2. Second Department of Propedeutic Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 3. N.S. Christeas Laboratory of Experimental Surgery and Surgical Research, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 4. Internal Medicine Department, Laiko General Hospital, University of Athens Medical School, Athens, Greece. 5. Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, U.S.A. 6. First Department of Surgery, Laiko General Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece. 7. Plastic Surgery Department and Burn Unit, Nicosia General Hospital, Nicosia, Cyprus. 8. Department of Neurology, Agia Sofia General Children's Hospital, Athens, Greece. 9. First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Abstract
BACKGROUND/AIM: Malignant melanoma is the most aggressive type of skin cancer, with increasing frequency and mortality. Melanoma is characterized by rapid proliferation and metastases. Malignant transformation of normal melanocytes is associated with imbalance between oncogenes' action and tumor suppressor genes. Mutations or inactivation of these genes plays an important role in the pathogenesis of malignant melanoma. Many target-specific agents improved progression-free survival but unfortunately metastatic melanoma remains incurable, so new therapeutic strategies are needed. The balance of histones' acetylation affects cell cycle progression, differentiation and apoptosis. Histone deacetylases (HDAC) are associated with different types of cancer. Histone deacetylase inhibitors (HDACI) are enzymes that inhibit the action of HDAC, resulting in block of tumor cell proliferation. A small number of these enzymes has been studied regarding their anticancer effects in melanoma. The purpose of this article was to review the therapeutic effect of HDACI against malignant melanoma, enlightening the molecular mechanisms of their action. MATERIALS AND METHODS: The MEDLINE database was used. The keywords/ phrases were; HDACI, melanoma, targeted therapies for melanoma. Our final conclusions were based on studies that didn't refer solely to melanoma due to their wider experimental data. Thirty-two articles were selected from the total number of the search's results. Only English articles published until March 2017 were used. RESULTS: Molecules, such as valproid acid (VPA), LBH589, LAQ824 (dacinostat), vorinostat, tubacin, sirtinol and tx-527, suberoyl bis-hydroxamic acid (SBHA), depsipeptide and Trichostatin A (TSA) have shown promising antineoplastic effects against melanoma. CONCLUSION: HDACI represent a promising agent for targeted therapy. More trials are required. Copyright
BACKGROUND/AIM: Malignant melanoma is the most aggressive type of skin cancer, with increasing frequency and mortality. Melanoma is characterized by rapid proliferation and metastases. Malignant transformation of normal melanocytes is associated with imbalance between oncogenes' action and tumor suppressor genes. Mutations or inactivation of these genes plays an important role in the pathogenesis of malignant melanoma. Many target-specific agents improved progression-free survival but unfortunately metastatic melanoma remains incurable, so new therapeutic strategies are needed. The balance of histones' acetylation affects cell cycle progression, differentiation and apoptosis. Histone deacetylases (HDAC) are associated with different types of cancer. Histone deacetylase inhibitors (HDACI) are enzymes that inhibit the action of HDAC, resulting in block of tumor cell proliferation. A small number of these enzymes has been studied regarding their anticancer effects in melanoma. The purpose of this article was to review the therapeutic effect of HDACI against malignant melanoma, enlightening the molecular mechanisms of their action. MATERIALS AND METHODS: The MEDLINE database was used. The keywords/ phrases were; HDACI, melanoma, targeted therapies for melanoma. Our final conclusions were based on studies that didn't refer solely to melanoma due to their wider experimental data. Thirty-two articles were selected from the total number of the search's results. Only English articles published until March 2017 were used. RESULTS: Molecules, such as valproid acid (VPA), LBH589, LAQ824 (dacinostat), vorinostat, tubacin, sirtinol and tx-527, suberoyl bis-hydroxamic acid (SBHA), depsipeptide and Trichostatin A (TSA) have shown promising antineoplastic effects against melanoma. CONCLUSION: HDACI represent a promising agent for targeted therapy. More trials are required. Copyright
Authors: Joann Lagman; Paula Sayegh; Christina S Lee; Sarah M Sulon; Alec Z Jacinto; Vanessa Sok; Natalie Peng; Deniz Alp; Jeffrey L Benovic; Christopher H So Journal: Mol Cell Biochem Date: 2019-07-30 Impact factor: 3.842