产品描述

Vincristine binds irreversibly to microtubules (Ki: 85 nM) and spindle proteins in S phase of the cell cycle and interferes with the formation of the mitotic spindle.

靶点活性

microtubule

体外活性

Vincristine inhibited tubulin addition (Ki, 0.085 microM). In L-cells, vincristine caused about 25% growth inhibition at 40 nM [1]. Vincristine inhibited SH-SY5Y cell proliferation in a time- and dose-dependent manner (IC50: 0.1 μM). VCR at 0.1 μM induced mitotic arrest and apoptosis, promoted the expression of caspase-3 and -9 and cyclin B while decreasing the expression of cyclin D at 6, 12, 18 and 24 h [2]. Axonal ultrastructural changes induced by vinblastine were studied in vitro at concentrations of 0.05 mM in the cat vagus nerve. Disruption of microtubules, the appearance of paracrystalline structures, and increase in neurofilaments were induced by vinblastine at 0.1 mM [3].

体内活性

Two multidrug-resistant P388 leukemia sublines, refractory to vincristine when grown as intraperitoneal ascites, were sensitive to necrosis induction when grown as subcutaneous tumours [4]. Following a single bolus injection of vincristine, the chimeras transplanted with wild-type or Mdr1ab KO marrow cells showed no reductions in WBC. In wild-type and KO mice, the absence of P-gp reduced the body clearance of vincristine, but that no further reduction occurred when Mrp1 was also absent [5].

细胞实验

SH-SY5Y cells at a logarithmic phase were seeded in 96-well plates (at 2x10^6/l) and incubated for 12 h until cells formed a monolayer. Wells were randomly chosen for treatment groups and a control group. For the treatment groups, cells were incubated with 200 μl of cell culture medium containing 0.001, 0.01, 0.1, 1 or 10 μM of VCR. In the control group, cells were grown in 200 μl cell culture medium only. Cells were incubated for another 24, 48 and 72 h and then 20 μl of 5 g/l MTT (0.1 mg/l final concentration) was added to each well. After 4 h of incubation, the cell culture supernatant was removed, 150 μl of DMSO was added to each well and the plate was shaken for 10 min. The absorbance of each well was detected at 490 nm (A value) on an ELISA plate reader. The growth inhibition rate of VCR-treated cells was calculated as: Growth inhibition rate % = [(average A value of control group - average A value of VCR-treated group)/average A value of control group] x 10^0%. This experiment was performed in triplicates [2]. Cell lines: B16 melanoma cell

动物实验

Vincristine (1 mg/ml) was diluted in saline and administered i.v. to wild-type and Mdr1ab/Mrp1 TKO mice, aged 10–14 weeks, at dose levels ranging between 0.125 and 4 mg/kg. Animals were monitored daily and killed when they lost more than 20% of their initial body weight. The MTD was defined as one dose step below the dose where more than one animal in that group had to be killed. Necropsies were performed in wild-type and Mdr1ab/Mrp1 TKO mice receiving vincristine at or near the MTD and killed 2 days later [5].

别名

硫酸长春新碱 , 22-Oxovincaleukoblastine sulfate , Leurocristine sulfate , Leurocristine

纯度

98%

分子量

923.04

分子式

C46H58N4O14S

CAS No.

2068-78-2

存储

Powder: -20°C for 3 years

In solvent: -80°C for 2 years

溶解度

DMSO: 93 mg/mL (100.8 mM)

Water: 92.3 mg/mL (100 mM)

Ethanol: <1 mg/mL

( < 1 mg/ml refers to the product slightly soluble or insoluble )

溶液 1

Saline: 30 mg/mL

参考文献

1. Jordan, M.A., et al. Comparison of the effects of vinblastine, vincristine, vindesine, and vinepidine on microtubule dynamics and cell proliferation in vitro. Cancer Res, 1985. 45(6): p. 2741-7.

2. Tu Y, et al. Vincristine induces cell cycle arrest and apoptosis in SH-SY5Y human neuroblastoma cells. Int J Mol Med. 2013 Jan;31(1):113-9.

3. Donoso, J.A., et al, Action of the vinca alkaloids vincristine, vinblastine, and desacetyl vinblastine amide on axonal fibrillar organelles in vitro. Cancer Res, 1977. 37(5): p. 1401-7.

4. Baguley, B.C., et al, Inhibition of growth of colon 38 adenocarcinoma by vinblastine and colchicine: evidence for a vascular mechanism. Eur J Cancer, 1991. 27(4): p. 482-7.

5. van Tellingen O, et al. P-glycoprotein and Mrp1 collectively protect the bone marrow from vincristine-induced toxicity in vivo. Br J Cancer. 2003 Nov 3;89(9):1776-82.

Note

For research use only.