Modification of the expression of adenosine 3′,5′-cyclic monophosphate-induced differentiated functions in neuroblastoma cells by beta-carotene and D-alpha-tocopheryl succinate.

Prasad, Kedar N.; Kentroti, Susan; Edwards‐Prasad, Judith; Vernadakis, Antonia; Imam, Mohammed; Carvalho, Eduardo Freese de; Kumar, Sanjay

doi:10.1080/07315724.1994.10718412

Cited by 30 publications

(24 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…48 Although it is far from understanding which cellular mechanisms caused the increase in intracellular cAMP in response to bcarotene in our experiments, a similar effect of this provitamin has been reported in neuroblastoma cells. 28 Our finding that exposure of the cells to retinol had similar effects as b-carotene suggest that the observed responses were mediated by retinol and/or its metabolites formed in the cells. This interpretation is in accord with a recent publication that has shown in BEAS-2B cells the formation of retinol, and its metabolites from b-carotene dissolved in DMSO after incubation for 48 and 72 hr.…”

Section: Discussionmentioning

confidence: 55%

“…An extensive literature search revealed that b-carotene has been shown to increase intracellular cAMP in neuroblastoma cells. 28 Our current experiments were therefore focused on the effects of b-carotene on cAMP and its associated downstream effectors as potential mediators of a stimulating effect on the proliferation of a human Clara cell-derived PAC cell line and its putative cell of origin (immortalized human small airway epithelial cells). Our data provide strong evidence in support of the hypothesis that b-carotene stimulates the growth of these cells via an increase in intracellular cAMP, activation of protein kinase A, activation of the cAMP response element (CREB) and activation of the extra cellular signal-regulated kinases (ERK1/2).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by β-carotene via activation of cAMP, PKA, CREB and ERK1/2

2005

View full text Add to dashboard Cite

An a-tocopherol, b-carotene supplementation trial (ATBC) and a chemoprevention trial with b-carotene and retinoids (CARET trial) were conducted in the 1990s in populations at risk for the development of lung cancer. Both trials had to be discontinued due to significant increases in lung cancer and cardiovascular mortality. Clinical trials to test the cancer preventive effects of b-carotene are still ongoing, and high concentrations of this provitamin are contained in numerous dietary supplements. Using a cell line derived from a human pulmonary adenocarcinoma (PAC) of Clara cell lineage and immortalized human small airway epithelial cells, our data show that low concentrations of b-carotene that can be realistically expected in human tissues after oral administration caused a significant increase in intracellular cAMP and activated PKA, as well as in phosphorylation of ERK1/2 and CREB. Furthermore, the proliferation of cells was significantly stimulated by identical concentrations of b-carotene as monitored by MTT assays. Control experiments with retinol also showed stimulation of cell proliferation and activation of PKA in both cell lines. In light of the fact that PAC is the leading type of lung cancer, these findings suggest that the growth promoting effects of b-carotene on this cancer type observed in our experiments may have contributed to the unfortunate outcome of the ATBC and CARET trials. This interpretation is supported by the fact that elevated levels of cAMP in the cardiovascular system play a major role in the genesis of cardiovascular disease, which was also greatly promoted in the CARET trial. Our data challenge the widely accepted view that b-carotene may be useful as a cancer preventive agent. ' 2005 Wiley-Liss, Inc.Key words: b-carotene; human lung adenocarcinoma; signal transduction; growth stimulation Lung cancer is the leading cause of cancer deaths in industrialized countries.1-3 Among the 4 major types of lung cancer recognized by the WHO classification (adenocarcinoma, small cell carcinoma, squamous cell carcinoma, large cell carcinoma) pulmonary adenocarcinoma (PAC) predominates today, accounting for about 60% of all lung cancer cases. 2,4,5 Smoking is a welldocumented risk factor for all types of lung cancers 6,7 while a high fat diet constitutes an additional risk factor for PAC.8-10 Human PAC may be derived from bronchiolar Clara cells or from alveolar type II cells. Immunohistochemistry is primarily used to identify cell lineage of this cancer type by using antibodies to the Clara cell-specific CC10 protein and the alveolar type II cell-specific surfactant. Using this technique, PAC of Clara cell lineage has been reported to account for about 50% of the PAC cases.11 By contrast, electron microscopic investigations have identified 90% of PAC as being derived from Clara cells.12 Recent reports have shown that exposure to cigarette smoke or the tobaccospecific carcinogen nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) downregulate the expression of the Clara cell-speci...

show abstract

Section: Discussionmentioning

confidence: 55%

mentioning

confidence: 99%

Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by β-carotene via activation of cAMP, PKA, CREB and ERK1/2

2005

View full text Add to dashboard Cite

show abstract

“…cAMP is known to induce terminal differentiation in neuroblastoma cells in culture [51]. ␣-TS and polar carotenoids [33], originally referred to as ␤-carotene [52], enhance the level of cAMP-induced differentiation in these cells [53] (Fig. 5).…”

Section: Antioxidant Vitamins In Combination With Certain Biological mentioning

confidence: 99%

High Doses of Multiple Antioxidant Vitamins: Essential Ingredients in Improving the Efficacy of Standard Cancer Therapy

Prasad

Kumar

Kochupillai

et al. 1999

Journal of the American College of Nutrition

129

View full text Add to dashboard Cite

Numerous articles and several reviews have been published on the role of antioxidants, and diet and lifestyle modifications in cancer prevention. However, the potential role of these factors in the management of human cancer have been largely ignored. Extensive in vitro studies and limited in vivo studies have revealed that individual antioxidants such as vitamin A (retinoids), vitamin E (primarily alpha-tocopheryl succinate), vitamin C (primarily sodium ascorbate) and carotenoids (primarily polar carotenoids) induce cell differentiation and growth inhibition to various degrees in rodent and human cancer cells by complex mechanisms. The proposed mechanisms for these effects include inhibition of protein kinase C activity, prostaglandin E1-stimulated adenylate cyclase activity, expression of c-myc, H-ras, and a transcription factor (E2F), and induction of transforming growth factor-beta and p21 genes. Furthermore, antioxidant vitamins individually or in combination enhance the growth-inhibitory effects of x-irradiation, chemotherapeutic agents, hyperthermia, and biological response modifiers on tumor cells, primarily in vitro. These vitamins, individually, also reduce the toxicity of several standard tumor therapeutic agents on normal cells. Low fat and high fiber diets can further enhance the efficacy of standard cancer therapeutic agents; the proposed mechanisms for these effects include the production of increased levels of butyric acid and binding of potential mutagens in the gastrointestinal tract by high fiber and reduced levels of growth promoting agents such as prostaglandins, certain fatty acids and estrogen by low fat. We propose, therefore, a working hypothesis that multiple antioxidant vitamin supplements together with diet and lifestyle modifications may improve the efficacy of standard and experimental cancer therapies.

show abstract

“…In light of the fact that 30% of the lung cancer cases in this trial were adenocarcinomas [54], a cancer family in which ␤-adrenergic, cAMP-dependent regulatory pathways predominate, in conjunction with the well documented role of ␤-adrenergic signaling in the modulation of cardiovascular disease [55], the ''chemopreventive'' agents used, may have promoted both diseases by stimulation of this pathway. In support of this hypothesis, in vitro studies have demonstrated that ␤-carotene enhances downstream effects mediated by cAMP and causes a transient increase in intracellular cAMP [56]. It has also been shown that natural and synthetic members of the retinoid family up-regulate the expression of ␤-adrenergic receptors and enhance cAMP-mediated signaling downstream of these receptors [57,58].…”

Section: Discussionmentioning

confidence: 93%

Neuroendocrine lung carcinogenesis in hamsters is inhibited by green tea or theophylline while the development of adenocarcinomas is promoted: implications for chemoprevention in smokers

et al. 2004

View full text Add to dashboard Cite

Modification of the expression of adenosine 3′,5′-cyclic monophosphate-induced differentiated functions in neuroblastoma cells by beta-carotene and D-alpha-tocopheryl succinate.

Abstract: These results suggest that beta-carotene and alpha-TS modify the effects of cAMP stimulating agents on differentiation of NB cells in culture.

Cited by 30 publications

References 15 publications

Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by β-carotene via activation of cAMP, PKA, CREB and ERK1/2

Growth stimulation of human pulmonary adenocarcinoma cells and small airway epithelial cells by β-carotene via activation of cAMP, PKA, CREB and ERK1/2

High Doses of Multiple Antioxidant Vitamins: Essential Ingredients in Improving the Efficacy of Standard Cancer Therapy

Neuroendocrine lung carcinogenesis in hamsters is inhibited by green tea or theophylline while the development of adenocarcinomas is promoted: implications for chemoprevention in smokers

Contact Info

Product

Resources

About