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

Jan, Chung‐Ren; Chiang, An-Jen; Chang, Hong‐Tai; Roan, Cherng-Jau; Lu, Yih-Chau; Jiann, Bang‐Ping; Ho, Chin-Man; Huang, Jong‐Khing

doi:10.1007/s00204-002-0420-0

Cited by 9 publications

(9 citation statements)

References 28 publications

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“…This infers that SERMs interact with the TG1 binding site. Indeed, it has been reported that pre‐treatment with a SERM (Tamoxifen ‐ TAM) inhibits the effect of TG1, increasing the intracellular Ca2 + concentration . We then performed further analysis by superimposing the AIT binding site (ERα) and the TG1 binding site (SERCA).…”

Section: Resultsmentioning

confidence: 75%

BioGPS: Navigating biological space to predict polypharmacology, off-targeting, and selectivity

et al. 2015

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The structural comparison of protein binding sites is increasingly important in drug design; identifying structurally similar sites can be useful for techniques such as drug repurposing, and also in a polypharmacological approach to deliberately affect multiple targets in a disease pathway, or to explain unwanted off-target effects. Once similar sites are identified, identifying local differences can aid in the design of selectivity. Such an approach moves away from the classical "one target one drug" approach and toward a wider systems biology paradigm. Here, we report a semiautomated approach, called BioGPS, that is based on the software FLAP which combines GRID Molecular Interactions Fields (MIFs) and pharmacophoric fingerprints. BioGPS comprises the automatic preparation of protein structure data, identification of binding sites, and subsequent comparison by aligning the sites and directly comparing the MIFs. Chemometric approaches are included to reduce the complexity of the resulting data on large datasets, enabling focus on the most relevant information. Individual site similarities can be analyzed in terms of their Pharmacophoric Interaction Field (PIF) similarity, and importantly the differences in their PIFs can be extracted. Here we describe the BioGPS approach, and demonstrate its applicability to rationalize off-target effects (ERα and SERCA), to classify protein families and explain polypharmacology (ABL1 kinase and NQO2), and to rationalize selectivity between subfamilies (MAP kinases p38α/ERK2 and PPARδ/PPARγ). The examples shown demonstrate a significant validation of the method and illustrate the effectiveness of the approach.

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Section: Resultsmentioning

confidence: 75%

BioGPS: Navigating biological space to predict polypharmacology, off-targeting, and selectivity

et al. 2015

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“…Because, in nondepolarizing cells, the majority of the basal calcium influx occurs through SOCC, the possible effect of tamoxifen on native TRPV6 activity was masked. Tamoxifen also exerts the same effect on SOCC activity in several cell types such as human oral cancer cells, CHO-K1 cells, human osteosarcoma cells, and ZR-75-1 human breast cancer cells (34)(35)(36)(37). This effect was shown not to be mediated by ERs.…”

Section: Discussionmentioning

confidence: 82%

Tamoxifen Inhibits TRPV6 Activity via Estrogen Receptor–Independent Pathways in TRPV6-Expressing MCF-7 Breast Cancer Cells

Bolanz

Kovács

Landowski

et al. 2009

Molecular Cancer Research

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The epithelial calcium channel TRPV6 is upregulated in breast carcinoma compared with normal mammary gland tissue. The selective estrogen receptor modulator tamoxifen is widely used in breast cancer therapy. Previously, we showed that tamoxifen inhibits calcium uptake in TRPV6-transfected Xenopus oocytes. In this study, we examined the effect of tamoxifen on TRPV6 function and intracellular calcium homeostasis in MCF-7 breast cancer cells transiently transfected with EYFP-C1-TRPV6. TRPV6 activity was measured with fluorescence microscopy using Fura-2. The basal calcium level was higher in transfected cells compared with nontransfected cells in calcium-containing solution but not in nominally calcium-free buffer. Basal influxes of calcium and barium were also increased. In transfected cells, 10 μmol/L tamoxifen reduced the basal intracellular calcium concentration to the basal calcium level of nontransfected cells. Tamoxifen decreased the transport rates of calcium and barium in transfected cells by 50%. This inhibitory effect was not blocked by the estrogen receptor antagonist, ICI 182,720. Similarly, a tamoxifen-induced inhibitory effect was also observed in MDA-MB-231 estrogen receptor-negative cells. The effect of tamoxifen was completely blocked by activation of protein kinase C. Inhibiting protein kinase C with calphostin C decreased TRPV6 activity but did not alter the effect of tamoxifen. These findings illustrate how tamoxifen might be effective in estrogen receptor-negative breast carcinomas and suggest that the therapeutic effect of tamoxifen and protein kinase C inhibitors used in breast cancer therapy might involve TRPV6-mediated calcium entry. This study highlights a possible role of TRPV6 as therapeutic target in breast cancer therapy.

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“…SERMs, including 4-OHT, regulate microRNA expression in other cell lines but no one has evaluated their effects in CHO-K1 cells (Jan et al, 2003). Here, we report that 4-OHT increases miR-29b-1 and miR-29a expression in CHO-K1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…TAM concentrations greater than 5 μM were reported to decrease viability of CHO-K1 cells (Jan et al, 2003). Here we showed that 100 nM and 1 μM 4-OHT treatment did not have any significant effect on the viability, migration, invasion, or colony forming ability of CHO-K1 cells-even when miR-29b-1 or miR-29a were overexpressed or their activity repressed by anti-miR transfection.…”

Section: Discussionmentioning

confidence: 99%

Regulation of miR-29b-1/a transcription and identification of target mRNAs in CHO-K1 cells

Muluhngwi

Richardson

Napier

et al. 2017

Molecular and Cellular Endocrinology

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miR-29b and miR-29a transcript levels were reported to increase in exponentially growing CHO-K1 cells. Here, we examine the regulation of miR-29b-1/a in CHO-K1 cells. We observed that 4-hydroxytamoxifen (4-OHT) increased pri-miR-29b-1 and pri-miR-29a transcription in CHO-K1 cells by activating endogenous estrogen receptor α (ERα). DICER, an established, bona fide target of miR-29b-1/a, was shown to be regulated by 4-OHT in CHO-K1 cells. We showed that miR-29b-1 and miR-29a serve a repressive role in cell proliferation, migration, invasion, and colony formation in CHO-K1 cells. To identify other targets of miR-29b-1 and miR-29a, RNA sequencing was performed by transfecting cells with anti-miR-29a, which inhibits both miR-29a and miR-29b-1, pre-miR-29b-1, and/or pre-miR-29a. In silico network analysis in MetaCore™ identified common and unique putative gene targets of miR-29b-1 and miR-29a. Pathway analysis of identified putative miR-29 targets were related to cell adhesion, cytoskeletal remodeling, and development. Further inquiry revealed regulation of pathways mediating responses to growth factor stimulus and cell cycle regulation.

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

Cited by 9 publications

References 28 publications

BioGPS: Navigating biological space to predict polypharmacology, off-targeting, and selectivity

BioGPS: Navigating biological space to predict polypharmacology, off-targeting, and selectivity

Tamoxifen Inhibits TRPV6 Activity via Estrogen Receptor–Independent Pathways in TRPV6-Expressing MCF-7 Breast Cancer Cells

Regulation of miR-29b-1/a transcription and identification of target mRNAs in CHO-K1 cells

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