Perspectives of protein kinase C (PKC) inhibitors as anti-cancer agents.
Although the role of serine/threonine protein kinase C (PKC) in malignant transformation is known from decades, an anti-PKC based approach in cancer therapy was hampered for the difficulties in developing pharmacological compounds able to selectively inhibit specific PKC isoforms. In this review, the role of PKC-epsilon and PKC-delta in promoting and counteracting tumor progression in different types of cancer, respectively, will be discussed in relationship with promising therapeutic perspectives based either on small molecule inhibitors or on natural compounds. Among a myriad of molecules able to modulate PKC activity, we will focus on the role of the enzastaurin and briostatin-1, which already entered clinical trials for several human cancers.
Department of Morphology and Embryology, University of Ferrara, via Fossato di Mortara, 44100, Ferrara, Italy.
A
A
Gonelli
C
C
Mischiati
R
R
Guerrini
R
R
Voltan
S
S
Salvadori
G
G
Zauli
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000502:physiology; D054713:Bryostatins / Q000627:therapeutic use; D002453:Cell Cycle; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D002986:Clinical Trials as Topic; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D010936:Plant Extracts / Q000627:therapeutic use; D051745:Protein Kinase C-delta / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000502:physiology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D000970:Antineoplastic Agents; D054713:Bryostatins; D007211:Indoles; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D016159:Tumor Suppressor Protein p53; C476094:herbal extract PG201; C046785:bryostatin 1; D051736:Proto-Oncogene Proteins c-mdm2; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; C504878:enzastaurin