Gossypol, a component in cottonseed, induced increases in cytosolic Ca 2+ levels in Chang liver cells

Cheng, Jin; Liu, C.-P.; Lo, Yuk-Keung; Chou, Kang Ju; Lin, Muh Chiou; Su, Warren; Law, Yee-Ping; Wang, J.-L.; Chen, W.-C.; Jan, C.-R.

doi:10.1016/s0041-0101(01)00194-5

Cited by 12 publications

(18 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This value is similar to the 10 lM observed in breast cancer cells, bladder cancer cells and renal tubular cells (Chang et al 2001(Chang et al , 2002Jan et al 2000). Tamoxifen increased [Ca 2+ ] i by releasing store-Ca 2+ and causing Ca 2+ influx because removing extracellular Ca 2+ partly reduced the tamoxifen-induced [Ca 2+ ] i increase.…”

Section: Discussionsupporting

confidence: 85%

“…Our results suggest that tamoxifen released Ca 2+ solely from thapsigargin-sensitive endoplasmic reticulum store, similar to the case in breast cancer cells, bladder cancer cells and renal tubular cells (Chang et al 2001(Chang et al , 2002Jan et al 2000). Our data also suggest that ryanodine-sensitive Ca 2+ stores did not contribute to tamoxifen-induced Ca 2+ release.…”

Section: Discussionsupporting

confidence: 81%

“…However, evidence accumulates that tamoxifen expresses additional effects such as inducing an immediate increase in [Ca 2+ ] i in several cell types in a manner unrelated to estrogen receptors. These cell types include renal tubular cells, bladder cancer cells, neutrophils, prostate cancer cells and glioma cells (Chang et al 2001(Chang et al , 2002Jan et al 2000). Because an unregulated [Ca 2+ ] i increase can alter many cell functions, the [Ca 2+ ] i -elevating effect of tamoxifen in cells from different tissues may be associated with the diverse in vivo effects of tamoxifen in different tissues.…”

Section: Discussionmentioning

confidence: 99%

“…In breast cancer cells, bladder cancer cells and renal tubular cells, it has been shown that tamoxifen (>5 lM) increases basal [Ca 2+ ] i and triggers cell death (Chang et al 2001(Chang et al , 2002Jan et al 2000). However, tamoxifen has been shown to inhibit Ca 2+ currents in neurosecretory cells (Greenberg et al 1987;Sartor et al 1988).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

The anti-breast cancer drug tamoxifen alters Ca2+ movement in Chinese hamster ovary (CHO-K1) cells

et al. 2002

View full text Add to dashboard Cite

The anti-breast cancer drug tamoxifen has recently been shown to cause an increase in intracellular free-Ca(2+) concentrations ([Ca(2+)](i)) in renal tubular cells, breast cells and bladder cells. Because tamoxifen is known to alter ovary function in human patients and in rats, the present study was aimed at exploring whether tamoxifen could alter Ca(2+) movement in Chinese hamster ovary (CHO-K1) cells. Cytosolic free-Ca(2+) levels in populations of cells have been explored by using fura-2 as a fluorescent Ca(2+) indicator. Tamoxifen at concentrations above 1 micro M increased [Ca(2+)](i) in a concentration-dependent manner with an EC(50) value of 8 micro M. The Ca(2+) signal was reduced by removing extracellular Ca(2+), but was not affected by nifedipine, verapamil, diltiazem or ICI 182,780 (an estrogen receptor antagonist). Pretreatment with 1 micro M thapsigargin (an endoplasmic reticulum Ca(2+) pump inhibitor) to deplete the endoplasmic reticulum Ca(2+) abolished 10 micro M tamoxifen-induced Ca(2+) release. Neither inhibition of phospholipase C with 2 micro M U73122 nor depletion of ryanodine-sensitive Ca(2+) stores with 50 micro M ryanodine affected tamoxifen-induced Ca(2+) release. Cell proliferation assays using ELISA revealed that overnight incubation with 5-10 micro M tamoxifen inhibited cell proliferation by 20%, and 20 micro M tamoxifen killed all cells. Together, the results suggest that, in CHO-K1 cells, tamoxifen induced a [Ca(2+)](i) increase by causing store-Ca(2+) release from the endoplasmic reticulum in an phospholipase C-independent manner, and by inducing Ca(2+) influx. The action of tamoxifen appears to be dissociated from estrogen receptor activation. Longer incubation with tamoxifen (>5 micro M) was cytotoxic.

show abstract

Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The anti-breast cancer drug tamoxifen alters Ca2+ movement in Chinese hamster ovary (CHO-K1) cells

et al. 2002

View full text Add to dashboard Cite

show abstract

“…To further test the suitability of our strategy for enhancing drug accumulation, we tested the sensitivity of a panel of 80 approved or experimental anticancer agents obtained from Discovery Microsource. This set of compounds includes DNA damaging agents, topoisomerase inhibitors, and compounds acting by unknown mechanisms such as garlicin and agents that do not damage DNA such as gossypol (Cheng et al, 2002;Qiu et al, 2002). The set of compounds also includes agents that would not act in yeast (such as nucleoside analogs) because of the absence of appropriate activating enzymes.…”

Section: Suppressing Drug Resistance Genes In Yeast 427mentioning

confidence: 99%

Enhancing Drug Accumulation inSaccharomyces cerevisiaeby Repression of Pleiotropic Drug Resistance Genes with Chimeric Transcription Repressors

Stepanov¹,

Nitiss²,

Neale³

et al. 2008

Mol Pharmacol

View full text Add to dashboard Cite

Yeast is a powerful model system for studying the action of small-molecule therapeutics. An important limitation has been low efficacy of many small molecules in yeast due to limited intracellular accumulation. We used the DNA binding domain of the pleiotropic drug resistance regulator pleiotropic drug resistance 1 (Pdr1) fused in-frame to transcription repressors to repress Pdr1-regulated genes. Expression of these chimeric regulators conferred dominant enhancement of sensitivity to a different class of compounds and led to greatly diminished levels of Pdr1p-regulated transcripts, including the yeast p-glycoprotein homolog Pdr5. Enhanced sensitivity was seen for a wide range of small molecules. Biochemical measurements demonstrated enhanced accumulation of rhodamine in yeast cells expressing the chimeric repressors. These repressors of Pdr1p-regulated transcripts can be introduced into large collections of strains such as the Saccharomyces cerevisiae deletion set and enhance the utility of yeast for studying drug action and for mechanism-based drug discovery.

show abstract

Gossypol affects ion transport in the isolated intestine of the seawater adapted eel, Anguilla anguilla

Trischitta

Faggio

2008

Comparative Biochemistry and Physiology Part A: Molecular &

View full text Add to dashboard Cite

Gossypol, a component in cottonseed, induced increases in cytosolic Ca 2+ levels in Chang liver cells

Cited by 12 publications

References 21 publications

The anti-breast cancer drug tamoxifen alters Ca2+ movement in Chinese hamster ovary (CHO-K1) cells

The anti-breast cancer drug tamoxifen alters Ca2+ movement in Chinese hamster ovary (CHO-K1) cells

Enhancing Drug Accumulation inSaccharomyces cerevisiaeby Repression of Pleiotropic Drug Resistance Genes with Chimeric Transcription Repressors

Gossypol affects ion transport in the isolated intestine of the seawater adapted eel, Anguilla anguilla

Contact Info

Product

Resources

About