Selective inhibition of human lung cancer cell growth by peptides derived from retinoblastoma protein.
Peptides containing retinoblastoma protein (RB) fragment 649-654 (LFYKKV) were tested for their ability to block the proliferation of RB-negative and RB-positive human non-small cell lung cancer (NSCLC) cells. These peptides potently restrained the growth of both types of tumor cells, as measured by metabolic (MTT) and cellular viability (trypan blue exclusion) assays. As such, and remarkably, the peptides were able to overcome the resistance of RB-positive cells usually observed with RB gene or protein replacement therapy. Compared to the overall performance of conventional chemotherapy tested in parallel, the peptides were more cytotoxic against RB-negative neoplastic cells and equipotent toward RB-positive tumor cells, yet less toxic toward normal human cells. Thus, these new molecules hold great promise to evolve into an efficient therapy for human lung cancer, a common malignancy still defying treatment and holding a poor prognosis, as well as for other human neoplasias.
Radulescu
R T
RT
Molecular Concepts Research, Guardinistrasse 47, Munich, D-81375, Germany.
Jaques
G
G
D000595:Amino Acid Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology; D002455:Cell Division / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016161:Genes, Retinoblastoma; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000494:pharmacology*; D016160:Retinoblastoma Protein / Q000737:chemistry / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D016160:Retinoblastoma Protein