c-Myc oncoprotein: cell cycle-related events and new therapeutic challenges in cancer and cardiovascular diseases.
Advanced stages of both cancer and atherosclerosis are characterized by a local increase in tissue mass that may be hard to control. This increase in tissue mass can be attributed to oxidation-sensitive modification of cell cycle-related events, including cellular proliferation, differentiation, and apoptosis, which could be secondary to alteration in the activity of tumor suppressor gene and oncogene products. The oncogene c-Myc has classically been considered to be involved in carcinogenesis and has more recently been implicated in both endothelial dysfunction and atherogenesis as well. Consequently, inhibition of c-Myc-dependent signaling has become a novel therapeutic opportunity and challenge in atherosclerosis and other cardiovascular diseases. Antioxidant strategies, RNA synthesis inhibitors such as mithramycin, and gene therapeutic approaches with antisense oligonucleotides against c-Myc are some of the promising strategies. In general, the increased biologic understanding of the participation of cell cycle events and targeting these events may enable to attenuate or prevent some of the complications of vascular and neoplastic diseases.
de Nigris
Filomena
F
Department of Pharmacological Sciences, University of Salerno, Salerno, Italy.
Sica
Vincenzo
V
Herrmann
Joerg
J
Condorelli
Gianluigi
G
Chade
Alejandro R
AR
Tajana
Gianfranco
G
Lerman
Amir
A
Lerman
Lilach O
LO
Napoli
Claudio
C
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002318:Cardiovascular Diseases / Q000378:metabolism* / Q000503:physiopathology; D002453:Cell Cycle; D018797:Cell Cycle Proteins; D002454:Cell Differentiation / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D015316:Genetic Therapy; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D017239:Paclitaxel / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D016271:Proto-Oncogene Proteins c-myc / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D020123:Sirolimus / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism
D000975:Antioxidants; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005419:Flavonoids; D010880:Piperidines; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D009569:Nitric Oxide; C077990:alvocidib; D017239:Paclitaxel; D020123:Sirolimus