title: Synergistic growth inhibition of cancer cells harboring the RET/PTC1 oncogene by staurosporine and rotenone involves enhanced cell death.
abstract: TPC-1 is a highly proliferative thyroid papillary carcinoma-derived cell line. These cells express the RET/PTC1 fusion protein, whose isoforms are characterized in this work. The bacterial alkaloid staurosporine and the plant extract rotenone are death-inducing drugs that have an inhibitory synergistic effect on the growth of TPC-1 cells. We show that this synergism is accompanied by an enhancement of the induction of cell death. Staurosporine alone induces cell cycle arrest in G₁, whereas rotenone induces arrest in G₂/M. We suggest that this additive pressure may drive cells to die, resulting in the synergistic interaction of the drug combination. These data emphasize the potential use of the staurosporine plus rotenone combination as an anticancer tool.
authors.affiliation: Instituto de Biologia Molecular e Celular, Universidade do Porto, Rua do Campo Alegre 823, 4150-180 Porto, Portugal. apgoncalves@ibmc.up.pt
authors.forename: Antonio Pedro
authors.initials: AP
authors.lastname: Goncalves
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Videira
authors.forename: Valdemar
authors.initials: V
authors.lastname: Maximo
authors.forename: Paula
authors.initials: P
authors.lastname: Soares
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D016923:Cell Death / Q000187:drug effects* / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D000072079:Patched Receptors; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology*; D019311:Staurosporine / Q000494:pharmacology*; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D015514:Oncogene Proteins, Fusion; D000072079:Patched Receptors; D011956:Receptors, Cell Surface; D012402:Rotenone; D051096:Proto-Oncogene Proteins c-ret; D019311:Staurosporine