gx-15-070 and Bone-Neoplasms

Osteosarcoma is the most frequent primary malignant bone tumor. Although survival has distinctly increased due to neoadjuvant chemotherapy in the past, patients with metastatic disease and poor response to chemotherapy still have an adverse prognosis. Hence, development of new therapeutic strategies is still of utmost importance.. Anticancer activity of KP46 against osteosarcoma cell models was evaluated as single agent and in combination approaches with chemotherapeutics and Bcl-2 inhibitors using MTT assay. Underlying mechanisms were tested by cell cycle, apoptosis and autophagy assays.. KP46 exerted exceptional anticancer activity at the nanomolar to low micromolar range, depending on the assay format, against all osteosarcoma cell models with minor but significant differences in IC. Together, our results identify KP46 as a new promising agent to supplement standard chemotherapy and possible future targeted therapy in osteosarcoma.

Topics: Antineoplastic Combined Chemotherapy Protocols; Autophagy; Bone Neoplasms; Cell Cycle; Cell Line, Tumor; Cell Movement; Drug Screening Assays, Antitumor; Drug Synergism; Humans; Indoles; Molecular Targeted Therapy; Organometallic Compounds; Osteosarcoma; Oxyquinoline; Pyrroles