Abstract
Osteosarcoma (OS) is the second most common primary malign bone neoplasm after multiple myeloma. Despite systemic chemotherapy, OS may give rise to local recurrences and metastases. Resistance to chemotherapy is not rare and is likely to occur in a high number of patients. Novel therapeutic approaches are required in order to efficiently treat osteosarcoma. Tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) and proteasome inhibitors (epoxomicin, MG132, bortezomib) represent new promising approaches in cancer treatment. The aim of our study is to elucidate the effects of epoxomicin alone or in combination with TRAIL in two TRAIL-resistant OS cell lines, Saos-2 and MG-63 namely. We determined the cytotoxic effects of epoxomicin and/or TRAIL on these two types of OS cells using dimethylthiazolyl 2,5 diphenyltetrazolium bromide (MTT) test and measured apoptosis markers such as pro-apoptotic Bax levels and caspase-3, -8, -9 activities. We used TUNEL assay to demonstrate apoptosis. We investigated dose and time dependent survival rates of OS cells and determined LD50 doses of epoxomicin and TRAIL on OS cell viability after 24, 48, and 72 hour incubations. Concurrent incubation with TRAIL and epoxomicin for 24 hour significantly increased caspase-3, caspase-8, caspase-9 activities and Bax protein levels. Our study demonstrated that the combination of TRAIL with epoxomicin enhances apoptosis, and overcomes TRAIL resistance, denoting promising results for OS therapy in the future.
Keywords: Apoptosis, Epoxomicin, MG-63, Osteosarcoma, Saos-2, TRAIL, TRAIL-resistance.
Graphical Abstract
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
Related Journals
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry
Current Analytical Chemistry
Current Computer-Aided Drug Design
Current Bioactive Compounds
Current Cancer Drug Targets
Combinatorial Chemistry & High Throughput Screening
Current Cancer Therapy Reviews
Current Diabetes Reviews
Current Drug Safety
Current Drug Targets
Related Books
Drug Addiction Mechanisms in the Brain
Botanicals and Natural Bioactives: Prevention and Treatment of Diseases
Software and Programming Tools in Pharmaceutical Research
Objective Pharmaceutics: A Comprehensive Compilation of Questions and Answers for Pharmaceutics Exam Prep
Biosurfactants: A Boon to Healthcare, Agriculture & Environmental Sustainability
Medicinal Chemistry of Drugs Affecting Cardiovascular and Endocrine Systems
Frontiers in Computational Chemistry
Frontiers in Clinical Drug Research - Anti-Cancer Agents
The Management of Metastatic Triple-Negative Breast Cancer: An Integrated and Expeditionary Approach
Advances in Dye Degradation
36