Cell cycle- and protein kinase C-specific effects of resiniferatoxin and resiniferonol 9,13,14-ortho-phenylacetate in intestinal epithelial cells

Frey, Mark R.; Clark, Jennifer A.; Bateman, Nicholas W.; Kazanietz, Marcelo G.; Black, Adrian R.; Black, Jennifer D.

doi:10.1016/j.bcp.2004.02.006

Cited by 9 publications

(17 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, species-specific differences between rat and human cell lines may explain the varying response of RTX between IEC-18 and normal urothelial cells. In agreement with other studies, the growth-suppressive effects of RTX were found to be independent of TRPV1 receptor and involved a decrease of cyclin D1 at mRNA and protein levels (Frey et al, 2004).…”

Section: Antineoplastic Activity Of Natural Capsaicin Analogssupporting

confidence: 92%

“…However, RTX differs by inducing prolonged cell cycle arrest (within G 0 phase) in IEC-18 rat ileal epithelial cells. Such differences can be explained by the fact that the IEC-18 is an immature epithelial cell line derived from rat intestinal crypt, and therefore its growth characteristics cannot be compared with normal primary adult epithelial cells (Frey et al, 2004). Additionally, species-specific differences between rat and human cell lines may explain the varying response of RTX between IEC-18 and normal urothelial cells.…”

Section: Antineoplastic Activity Of Natural Capsaicin Analogsmentioning

confidence: 99%

“…1B9). Frey et al (2004) investigated the growth-inhibitory activity of ROPA on IEC-18 cells (Frey et al, 2004). ROPA was found to induce a transient protein kinase C-dependent cell cycle arrest in G 1 phase.…”

Section: Antineoplastic Activity Of Natural Capsaicin Analogsmentioning

confidence: 99%

See 2 more Smart Citations

Anticancer Activity of Natural and Synthetic Capsaicin Analogs

Friedman

Nolan

Brown

et al. 2017

J Pharmacol Exp Ther

View full text Add to dashboard Cite

The nutritional compound capsaicin is the major spicy ingredient of chili peppers. Although traditionally associated with analgesic activity, recent studies have shown that capsaicin has profound antineoplastic effects in several types of human cancers. However, the applications of capsaicin as a clinically viable drug are limited by its unpleasant side effects, such as gastric irritation, stomach cramps, and burning sensation. This has led to extensive research focused on the identification and rational design of second-generation capsaicin analogs, which possess greater bioactivity than capsaicin. A majority of these natural capsaicinoids and synthetic capsaicin analogs have been studied for their pain-relieving activity. Only a few of these capsaicin analogs have been investigated for their anticancer activity in cell culture and animal models. The present review summarizes the current knowledge of the growth-inhibitory activity of natural capsaicinoids and synthetic capsaicin analogs. Future studies that examine the anticancer activity of a greater number of capsaicin analogs represent novel strategies in the treatment of human cancers.

show abstract

Section: Antineoplastic Activity Of Natural Capsaicin Analogssupporting

confidence: 92%

Section: Antineoplastic Activity Of Natural Capsaicin Analogsmentioning

confidence: 99%

See 1 more Smart Citation

Anticancer Activity of Natural and Synthetic Capsaicin Analogs

Friedman

Nolan

Brown

et al. 2017

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Induction of p21 Cip1 is also involved in the ability of this isozyme to delay S phase transit and induce G2/M arrest (Frey et al, 1997; Oliva et al, 2008). Our analysis in intestinal epithelial cells indicated that downregulation of cyclin D1 represents one of the earliest effects of PKCα signaling (Frey et al, 2004; Hizli et al, 2006): PKCα-induced loss of cyclin D1 results from translational and transcriptional inhibition, mediated by activation of the translational repressor 4E-BP1 and downregulation of the Id family of transcription factors, respectively (Clark et al, 2004; Hizli et al, 2006; Guan et al, 2007; Hao et al, 2011). Suppression of cyclin D1 expression by PKCα can involve different intermediate signaling events, including activation of the ERK/MAPK pathway (Clark et al, 2004; Hizli et al, 2006; Guan et al, 2007; Hao et al, 2011) and RORα-mediated suppression of Wnt/β-catenin signaling (Bird et al, 1998).…”

Section: Pkcs and The Cell Cyclementioning

confidence: 91%

Protein kinase C signaling and cell cycle regulation

Black¹,

Black²

2013

Front. Immun.

View full text Add to dashboard Cite

A link between T cell proliferation and the protein kinase C (PKC) family of serine/threonine kinases has been recognized for about 30 years. However, despite the wealth of information on PKC-mediated control of, T cell activation, understanding of the effects of PKCs on the cell cycle machinery in this cell type remains limited. Studies in other systems have revealed important cell cycle-specific effects of PKC signaling that can either positively or negatively impact proliferation. The outcome of PKC activation is highly context-dependent, with the precise cell cycle target(s) and overall effects determined by the specific isozyme involved, the timing of PKC activation, the cell type, and the signaling environment. Although PKCs can regulate all stages of the cell cycle, they appear to predominantly affect G0/G1 and G2. PKCs can modulate multiple cell cycle regulatory molecules, including cyclins, cyclin-dependent kinases (cdks), cdk inhibitors and cdc25 phosphatases; however, evidence points to Cip/Kip cdk inhibitors and D-type cyclins as key mediators of PKC-regulated cell cycle-specific effects. Several PKC isozymes can target Cip/Kip proteins to control G0/G1 → S and/or G2 → M transit, while effects on D-type cyclins regulate entry into and progression through G1. Analysis of PKC signaling in T cells has largely focused on its roles in T cell activation; thus, observed cell cycle effects are mainly positive. A prominent role is emerging for PKCθ, with non-redundant functions of other isozymes also described. Additional evidence points to PKCδ as a negative regulator of the cell cycle in these cells. As in other cell types, context-dependent effects of individual isozymes have been noted in T cells, and Cip/Kip cdk inhibitors and D-type cyclins appear to be major PKC targets. Future studies are anticipated to take advantage of the similarities between these various systems to enhance understanding of PKC-mediated cell cycle regulation in T cells.

show abstract

“…24 It has been demonstrated that, in intestinal epithelial cells, an anti-proliferative regulation of Cyclin D1 was modulated by PKCα signaling. 25 On the other hand, PKCα growth-stimulatory effects have been shown in glioma cells, osteoblasts, chick embryo hepatocytes, hepatocellular carcinoma cells and myoblasts, among others. 15 Proliferative effects of PKCα included increased levels of Cyclin D1 and cdk4 and increased cyclin/cdk2 complex activity.…”

Section: Human Erythroleukemia Cells K562 Overexpressing Plcβ1mentioning

confidence: 99%