Multiple effects of paclitaxel are modulated by a high c-myc amplification level.

• Paclitaxel affects microtubule stability by binding to beta-tubulin, thus leading to cell accumulation in the G(2)/M phase, polyploidization, and apoptosis. Because both cell proliferation and apoptosis could be somehow regulated by the protooncogene c-myc, in this work we have investigated whether the c-myc amplification level could modulate the multiple effects of paclitaxel. To this aim, paclitaxel was administered to SW613-12A1 and -B3 human colon carcinoma cell lines (which are characterized by a high and low c-myc endogenous amplification level, respectively), and to the B3mycC5 cell line, with an enforced exogenous expression of c-myc copies. In this experimental system, we previously demonstrated that a high endogenous/exogenous level of amplification of c-myc enhances serum deprivation- and DNA damage-induced apoptosis. Accordingly, the present results indicate that a high c-myc amplification level potentiates paclitaxel cytotoxicity, confers a multinucleated phenotype, and promotes apoptosis to a great extent, thus suggesting that c-myc expression level is relevant in modulating the cellular responses to paclitaxel. We have recently shown in HeLa cells that the phosphorylated form of c-Myc accumulates in the nucleus, as distinct nucleolar and extranucleolar spots; here, we demonstrated that, after the treatment with paclitaxel, phosphorylated c-Myc undergoes redistribution, becoming diffused in the nucleoplasm.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Nyckelord

Antineoplastic Agents

Phytogenic

pharmacology

Apoptosis

drug effects

genetics

Carcinoma

drug therapy

genetics

metabolism

Cell Compartmentation

drug effects

physiology

Cell Division

drug effects

genetics

Cell Nucleus

drug effects

genetics

metabolism

Colonic Neoplasms

drug therapy

genetics

metabolism

Eukaryotic Cells

drug effects

metabolism

Gene Amplification

drug effects

genetics

Gene Dosage

Genes

myc

drug effects

physiology

Humans

Neoplasms

drug therapy

genetics

metabolism

Paclitaxel

pharmacology

Phosphorylation

drug effects

Tumor Cells

Cultured

Up-Regulation

drug effects

genetics

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