What question did this study set out to answer?

To examine the upstream triggers and functional role of cell membrane fluidification and the sodium-hydrogen exchanger NHE1 during cisplatin-mediated apoptosis in colon cancer cells.

August 15, 2007Cancer Research

Cisplatin-Induced Apoptosis Involves Membrane Fluidification via Inhibition of NHE1 in Human Colon Cancer Cells

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Authors

ARAmélie RébillardInstitut Universitaire de France XTXavier TekpliOslo University Hospital OMOlivier MeuretteUniversité Claude Bernard Lyon 1

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Implication

In vitro study reveals cisplatin triggers apoptosis via NHE1 inhibition and membrane fluidification in colon cancer cells, indicating an alternative target to enhance chemotherapy sensitivity.

Key Points

To examine the upstream triggers and functional role of cell membrane fluidification and the sodium-hydrogen exchanger NHE1 during cisplatin-mediated apoptosis in colon cancer cells.
Exposed HT29 human colon cancer cells and PS120 fibroblasts (NHE1-expressing vs. NHE1-deficient) to cisplatin.
Modulated membrane dynamics and signaling using stabilizing agents (cholesterol, monosialoganglioside-1) and the selective NHE1 inhibitor cariporide.
Measured intracellular acidification, acid sphingomyelinase activation, ceramide production, lipid raft clustering, Fas receptor aggregation, and DNA adduct formation.
Membrane-stabilizing agents blocked Fas death receptor clustering and significantly inhibited apoptosis without changing cisplatin uptake or DNA adduct formation.
Cisplatin rapidly inhibited NHE1 to induce intracellular acidification, which stimulated acid sphingomyelinase activation, membrane ceramide production, and membrane fluidity; these effects were prevented by cariporide.
PS120 cells expressing functional NHE1 exhibited substantially greater apoptotic sensitivity to cisplatin compared to NHE1-deficient counter-cells.

Cite This Study

Rébillard et al. (2007) studied this question.

synapsesocial.com/papers/6a710d5835aa2c282ce25e2d https://doi.org/10.1158/0008-5472.can-07-0353

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Implication

In vitro study reveals cisplatin triggers apoptosis via NHE1 inhibition and membrane fluidification in colon cancer cells, indicating an alternative target to enhance chemotherapy sensitivity.

Cisplatin-Induced Apoptosis Involves Membrane Fluidification via Inhibition of NHE1 in Human Colon Cancer Cells

Discussion

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Implication

Key Points

Cite This Study

Cisplatin-Induced Apoptosis Involves Membrane Fluidification via Inhibition of NHE1 in Human Colon Cancer Cells

Discussion

Member takes

Implication

Key Points

Cite This Study

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