Docetaxel is a clinically well-established anti-mitotic chemotherapy medication. Docetaxel binds to microtubules reversibly with high affinity and has a maximum stoichiometry of 1 mole docetaxel per mole tubulin in microtubules. It has also been found to lead to the phosphorylation of oncoprotein bcl-2, which is apoptosis-blocking in its oncoprotein form. Docetaxel exhibits cytotoxic activity on breast, colorectal, lung, ovarian, gastric, renal and prostate cancer cells. Docetaxel does not block disassembly of interphase microtubules and so does not prevent entry into the mitotic cycle, but does block mitosis by inhibiting mitotic spindle assembly. Docetaxel activity is significantly greater in ovarian and breast tumours than for lung tumours. Docetaxel prevents microtubule depolymerization and disassembly in the absence of GTP.
|Cell lines||A549, HCT-116, NCI-H838, KB-3-1, MX-1W, NCI-H1299 and DLD-1 cells|
|Preparation method||Cell Proliferation Assays
Cytotoxicity was assessed by growing cells in the presence of agents for 72 h. Cell survival was measured by the sulforhodamine B (SRB) protein stain method or the ATP-binding assay using the Cell-Titer Glo Luminescent Reporter (GLR) System (Promega, Inc., Madison, WI). The SRB assay was done as previously described (23). For the GLR system, cells were plated robotically at approximately 50% confluency in a 384-well plate and allowed to attach for 12 h at 37°C/5% CO2. After diluting test agents using BioMek 2000 robotic system (Beckman Instruments, Fullerton, CA), agents were added to each well and incubated for 72 h. ATP binding and stabilization of the luminescent signal were performed according to manufacturer's protocol (Promega) following tumor cell lysis. Absorbance was read on a Victor V multilabel plate reader (Perkin-Elmer, Gaithersburg, MD) at a wavelength of A595 and data collected using Wallac 1420 Workstation software.
|Incubation time||72 h|
|Animal models||Athymic nu/nu female mice bearing Lox melanoma cells, KB-3-1 cells and A375SM melanoma cells tumour xenograft model|
|Formulation||1.4% ethanol/3.5% polysorbate 80 in saline|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|Animal A (mg/kg) = Animal B (mg/kg) multiplied by||Animal B Km|
|Animal A Km|
For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.
|Solubility||DMSO 150 mg/mL
Ethanol 150 mg/mL
Suppression of acquired docetaxel resistance in prostate cancer through depletion of notch- and hedgehog-dependent tumor-initiating cells.
Domingo-Domenech J, et al. Cancer Cell. 2012 Sep 11;22(3):373-88. PMID: 22975379.
Docetaxel: a review of its use in metastatic breast cancer.
Lyseng-Williamson KA, et al. Drugs. 2005;65(17):2513-31. PMID: 16296875.
MAC-321, a novel taxane with greater efficacy than paclitaxel and docetaxel in vitro and in vivo.
Sampath D, et al. Mol Cancer Ther. 2003 Sep;2(9):873-84. PMID: 14555706.
|Related Microtubule Products|
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Estramustine phosphate sodium is an antimicrotubule chemotherapy agent; arrests prostate cancer cells in the G2/M phase of the cell cycle.
Docetaxel trihydrate(Taxotere trihydrate), an analog of taxol, is an inhibitor of depolymerisation of microtubules through binding to stabilized microtubules.
Albendazole is a tubulin polymerization or assembly inhibitor, used for the treatment of a variety of parasitic worm infestations.
INH6 is a potent Hec1 inhibitor, which specifically disrupts the Hec1/Nek2 interaction and causes chromosome mis-alignment.
ELR510444 is a novel microtubule disruptor; inhibits MDA-MB-231 cell proliferation with IC50 of 30.9 nM; not a substrate for the P-glycoprotein compound transporter and retains activity in βIII-tubulin-overexpressing cell lines.
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