Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Etoposide drug resistance

Etoposide (XV) is a semisynthetic gylcoside derivative of podophyllotoxin, which is one of the most extensively used anticancer drugs in the treatment of various types of tumors [64,65]. The anticancer activity of this drug is mainly due to its ability to inhibit an ubiquitous and essential enzyme human DNA topo II [66,67]. Despite its extensive use in the treatment of cancers, it has several limitations, such as poor water solubility, drug resistance, metabolic inactivation, myelosuppression, and toxicity [68]. In order to overcome these... [Pg.63]

Etoposide (VePesid) is a semisynthetic derivative of podophyllotoxin that is produced in the roots of the American mandrake, or May apple. Unlike podophyllotoxin and vinca alkaloids, etoposide does not bind to microtubules. It forms a complex with the enzyme topoiso-merase II, which results in a single-strand breakage of DNA. It is most lethal to cells in the S- and Gj-phases of the cell cycle. Drug resistance to etoposide is thought to be caused by decreased cellular drug accumulation. [Pg.648]

In the kidney, MRP3 (ABCC3) is expressed at the basolateral membrane of distal renal tubular cells and carries glucuroconjugated compounds and other molecules from the internal tubular cell into the blood. MRP3 was shown to confer cellular drug resistance to etoposide, tenoposide and vincristine [120f,gj. [Pg.59]

It was observed earlier that over expression of human N-terminal domain in yeast confers resistance to high concentrations of etoposide. The observed phenotype was proposed to be due to the competition of the excess of the N-terminal domain with the frill length enzyme for a limiting pool of inhibitor. So future challenge in the parasite topoisomerase II would be to develop drug resistant parasite strains and to see what causes this resistance and also to check what effect the individual domains of the enzyme have on the drug protein interaction in the context of the full-length enzyme. [Pg.109]

The vinca alkaloids vinblastine and vincristine are capable of producing the MDR phenotype in a wide variety of cell types. Furthermore, cells that are made resistant to antitumor drugs such as doxorubicin, actinomy-cin D, or the epipodophyllotoxins etoposide (VP-16) and teniposide (VM-26) are often resistant to the effects of the bisindole alkaloids. The structural and mechanistic diversity of these compounds is even more striking against the backdrop of collateral resistance. [Pg.196]

Short term treatment with TPA sensitized human 2008 ovarian carcinoma cells to cis-platin. This sensitization disappeared completely by seven hours after treatment, indicating that not inhibition, but activation of PKC sensitizes 2008 cells to the antiproliferative activity of cis-platin (Isonishi et al., 1990). Pretreatment of HeLa cells with TPA or PdBu caused a 9-fold increase in cellular sensitivity to cis-platin and 2.5-fold to melphalan, but had now effect on the antiproliferative activity of bleomycin, adriamycin, vincristine, or mitomycin C. The sensitization of HeLa cells by TPA was associated with a 6-fold stimulation of PKC activation and a concentration- and time-dependent increase in cellular platinum content. (Basu et al. 1990). PKC activity was found to be decreased significantly in cis-platin-resistant human small cell lung H69/CP cancer cells compared to the drug-sensitive variant. A similar reduction in PKC activity was noted in ovarian carcinoma 2008 cells that were resistant to cis-platin. A modest decrease in PKC activity was also observed in etoposide-resistant H69 cells but not in taxol-resistant H69 cells or bleomycin-resistant human head and neck carcinoma A-253 cells (Basu et al., 1996), indicating that reduced PKC activity leads to decreased sensitivity in this system. [Pg.57]

Three classes of plant-derived drugs, the vinca alkaloids (vincristine, vinblastine, and vinorelbine), the epipodo-phyllotoxins (etoposide and teniposide and the tax-anes (paclitaxel and taxotere), are used in cancer chemotherapy. These classes differ in their structures and mechanisms of action but share the multidrug resistance mechanism, since they are all substrates for the multidrug transporter P-glycoprotein. [Pg.648]

Reconstitution of full-length BRCAl into mouse embryonic fibroblast cells with a disrupted BRCAl led to an increase in resistance to several DNA damaging agents, including the platinum compounds carboplatin and oxaliplatin, the topoisomerase 1 drugs irinotecan and topotecan, and the topoisomerase 11 drugs doxorubicin and etoposide (61). [Pg.238]


See other pages where Etoposide drug resistance is mentioned: [Pg.348]    [Pg.174]    [Pg.45]    [Pg.57]    [Pg.58]    [Pg.83]    [Pg.84]    [Pg.88]    [Pg.407]    [Pg.27]    [Pg.243]    [Pg.105]    [Pg.289]    [Pg.702]    [Pg.2378]    [Pg.2500]    [Pg.121]    [Pg.740]    [Pg.79]    [Pg.5]    [Pg.126]    [Pg.127]    [Pg.568]    [Pg.702]    [Pg.74]    [Pg.75]    [Pg.79]    [Pg.89]    [Pg.21]    [Pg.22]    [Pg.273]    [Pg.337]    [Pg.11]    [Pg.349]    [Pg.381]    [Pg.632]    [Pg.232]    [Pg.242]    [Pg.84]    [Pg.11]    [Pg.386]    [Pg.174]    [Pg.250]   
See also in sourсe #XX -- [ Pg.243 ]




SEARCH



Drug resistance

Drug-resistant

Etoposide

Etoposide resistance

© 2024 chempedia.info