Protein kinase C (PKC) family in cancer progression

Koivunen, Jussi; Aaltonen, Vesa; Peltonen, Juha

doi:10.1016/j.canlet.2005.03.033

Cited by 222 publications

(185 citation statements)

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“…A c c e p t e d M a n u s c r i p t 4 cancer therapy [3,[5][6][7]. While PKC-- and - are frequently associated with proliferative effects being involved in the tumorigenesis of various cancers, PKC- is often linked to antiproliferative/pro-apoptotic effects in mammals [3,[5][6][7].…”

Section: Page 4 Of 47mentioning

confidence: 99%

Section: Page 4 Of 47mentioning

confidence: 99%

“…While PKC-- and - are frequently associated with proliferative effects being involved in the tumorigenesis of various cancers, PKC- is often linked to antiproliferative/pro-apoptotic effects in mammals [3,[5][6][7]. Consequently, selective activators of PKC-, - and - are considered tumour promoters, while selective activators of PKC- represent promising anti-cancer drugs [3,[5][6][7]. Although PKC- and - display a high degree of homology and similar substrate specificity, suggesting similar targets in signal transduction pathways for both nPKCs, they are frequently described as mediating quite contrasting physiological effects [3,5,6].…”

Section: Page 4 Of 47mentioning

confidence: 99%

“…Consequently, selective activators of PKC-, - and - are considered tumour promoters, while selective activators of PKC- represent promising anti-cancer drugs [3,[5][6][7]. Although PKC- and - display a high degree of homology and similar substrate specificity, suggesting similar targets in signal transduction pathways for both nPKCs, they are frequently described as mediating quite contrasting physiological effects [3,5,6]. However, although several studies suggest that PKC- favours life over death [3,[5][6][7], recent research works also showed that PKC- activation can contribute to apoptosis.…”

Section: Page 4 Of 47mentioning

confidence: 99%

“…Although PKC- and - display a high degree of homology and similar substrate specificity, suggesting similar targets in signal transduction pathways for both nPKCs, they are frequently described as mediating quite contrasting physiological effects [3,5,6]. However, although several studies suggest that PKC- favours life over death [3,[5][6][7], recent research works also showed that PKC- activation can contribute to apoptosis. For example, it was demonstrated that ethanol induces apoptosis in hepatocytes via activation of the nPKC isoforms, PKC- and - [8].…”

Section: Page 4 Of 47mentioning

confidence: 99%

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Selective activation of protein kinase C-δ and -ɛ by 6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U)

Coutinho

Pereira

Simões

et al. 2009

Biochemical Pharmacology

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6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U) is a diterpene compound isolated from Plectranthus grandidentatus with an antiproliferative effect on several human cancer cell lines. Herein, we studied the modulatory activity of coleon U on individual isoforms of the three protein kinase C (PKC) subfamilies, classical (cPKC- and -I), novel (nPKC- and -) and atypical (aPKC-), using a yeast PKC assay. The results showed that, whereas the PKC activator phorbol-12-myristate-13-acetate (PMA) activated every PKC tested except aPKC coleon U had no effect on aPKC and cPKCs. Besides, the effect of coleon U on nPKCs was higher than that of PMA. This revealed that coleon U was a potent and selective activator of nPKCs The isoform-selectivity of coleon U for nPKC- and - was confirmed using an in vitro PKC assay. Most importantly, while PMA activated nPKCs inducing an isoform translocation from the cytosol to the plasma membrane and a G2/M cell cycle arrest, coleon U induced nPKCs translocation to the nucleus and a metacaspase-and mitochondrial-dependent apoptosis. This work therefore reconstitutes in yeast distinct subcellular translocations of a PKC isoform and the subsequent distinct cellular responses reported for mammalian cells. Together, our study identifies a new isoform-selective PKC activator with promising pharmacological applications. Indeed, since coleon U has no effect on cPKCs and aPKC recognized as anti-apoptotic proteins, and selectively induces an apoptotic pathway dependent on nPKC- and - activation, it represents a promising compound for evaluation as an anti-cancer drug.

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Section: Page 4 Of 47mentioning

confidence: 99%

Section: Page 4 Of 47mentioning

confidence: 99%

Section: Page 4 Of 47mentioning

confidence: 99%

Section: Page 4 Of 47mentioning

confidence: 99%

Section: Page 4 Of 47mentioning

confidence: 99%

See 3 more Smart Citations

Selective activation of protein kinase C-δ and -ɛ by 6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U)

Coutinho

Pereira

Simões

et al. 2009

Biochemical Pharmacology

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A Non‐Mulberry Silk Fibroin Protein Based 3D In Vitro Tumor Model for Evaluation of Anticancer Drug Activity

Talukdar

Kundu

2012

Adv Funct Materials

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The limitations of clinical chemotherapy are credited primarily to drug resistance. Effective development and screening of new drugs require appropriate in vitro tumor models that resemble the in vivo situation to evaluate drug efficiency and to decrease the use of experimental animals. 3D in vitro model systems that are able to mimic in vivo microenvironments are now highly sought after in cancer research. Here, the characteristics of breast cancer cell line MDA‐MB‐231 cells on 3D, and 2D Antheraea mylitta silk matrices and tissue culture plates are compared. After long term culture of breast cancer cells in the silk scaffold, the engineered tumor construct shows different zones of cell proliferation, such as an avascular tumor. Silk fibroin matrix 3D tumor models are studied for the evaluation of various anticancer drugs. The cytotoxic effects of three different drugs (Paclitaxel, Celecoxib, and ZD6474) at different concentrations are evaluated for MDA‐MB‐231 grown on 2D films as well as on a 3D fibroin scaffold. Higher drug concentrations are required to achieve a comparable reduction in cell viability and invasive potential in 3D culture. Combinatorial treatment of drugs at IC50 concentrations result in up to 84% death of cancer cells. The results indicate that 3D in vitro tumor models may be better systems to evaluate cancer treatment strategies.

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Molecular mechanisms involved in Ras inactivation: the annexin A6–p120GAP complex

Grewal

Enrich

2006

BioEssays

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In mammalian cells, a complex network of signaling pathways tightly regulates a variety of cellular processes, such as proliferation and differentiation. New insights from one of the most-important signaling cascades involved in oncogenesis, the Ras-Raf-MAPK pathway, suggest that the subcellular localisation and assembly of signaling modules of this pathway is crucial to control the biological response. This commonly requires membrane targeting events that are mediated by adaptor/scaffold proteins. Of particular interest is the translocation and complex formation of GTPase-activating proteins (GAPs), such as p120GAP, at the plasma membrane to inactivate Ras. Recent studies indicate that one member of the annexin family, annexin A6 acts as a targeting protein for p120GAP. This review discusses how annexin A6 modulates the involvement of negative regulators of the Ras-Raf-MAPK pathway contributing to Ras inactivation.

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Protein kinase C (PKC) family in cancer progression

Cited by 222 publications

References 68 publications

Selective activation of protein kinase C-δ and -ɛ by 6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U)

Selective activation of protein kinase C-δ and -ɛ by 6,11,12,14-tetrahydroxy-abieta-5,8,11,13-tetraene-7-one (coleon U)

A Non‐Mulberry Silk Fibroin Protein Based 3D In Vitro Tumor Model for Evaluation of Anticancer Drug Activity

Molecular mechanisms involved in Ras inactivation: the annexin A6–p120GAP complex

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