Recombinant Human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Selectively Induces Apoptosis in Malignant Melanoma
Katherine A. Turner1,2, Daniel J. Lindner3, and Michael Kalafatis1,2,3,4*
Affiliation
- 1Department of Chemistry, Cleveland State University
- 2Center for Gene Regulation in Health and Disease (GRHD)
- 3Taussig Cancer Institute, Cleveland Clinic Foundation
- 4Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic Foundation
Corresponding Author
Michael Kalafatis, Cleveland State University, Department of Chemistry, 2351 Euclid Avenue, Science and Research Center SR370, Cleveland, Ohio 44115, Tel: (216) 687-2460; Fax: (216) 687-9298; E-mail: m.kalafatis@csuohio.edu
Citation
Kalafatis, M., et al. Recombinant Human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand Selectively Induces Apoptosis in Malignant Melanoma. (2017) Int J Cancer Oncol 4(1): 1- 8.
Copy rights
© 2017 Kalafatis, M. This is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Keywords
Abstract
Skin cancer is among the most commonly-diagnosed cancers with malignant melanoma being associated with the highest rate of metastasis and death. In its early stage, melanoma is easily cured, but the prognosis associated with metastatic malignant melanoma remains very poor and is one of the most treatment-refractory malignancies. This work was undertaken to assess the effectiveness and safety of recombinant human Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (rhTRAIL) as a potential therapeutic for malignant melanoma. rhTRAIL is the optimized version of the naturally-occurring death-ligand TRAIL. TRAIL shows cancer cell specificity through its innate ability to induce apoptosis in a broad range of transformed human cells while showing no toxicity toward normal healthy cells. Utilizing malignant melanoma A375 cells and normal human melanocytes, the efficacy and safety of rhTRAIL was determined in vitro and in vivo through nude mice A375 xenografts. rhTRAIL induced significant levels of apoptosis in malignant melanoma cells in vitro and at the same time did not induce apoptosis in non-transformed melanocytes. rhTRAIL showed remarkable in vivo potency and was able to inhibit the growth of established melanoma tumors while showing no toxicity towards the mice model. These data suggest that rhTRAIL is a valid candidate for the treatment of malignant melanoma, displaying significant anti-tumor activity with sustainably less negative side effects than traditional therapies.
