Vincristine

Vincristine is an inhibitor of polymerization of microtubules by binding to tubulin with IC₅₀ of 32μM in a cell-free assay. Vincristine can induces apoptosis^[1].

Vincristine (100nM; 48h) induces distinct death programs in primary ALL cells depending on cell cycle phase, and cells in G1 are susceptible to perturbation of interphase microtubules^[2].Vincristine (5nM; 4, 8, 24h) triggers a cascade of axon pathology, causing mitochondrial dysfunction that leads to elevated axonal ROS levels and SARM1-dependent axon degeneration^[3].Vincristine (0.3-10nM; 48h) and SAHA on T cell leukemic cells resulted in a change in microtubule dynamics contributing to M phase arrest followed by induction of the apoptotic pathway^[4].

Vincristine (Pre: <10μg or 0.5mg/kg; Post: 10μg; ip; 25d) causes swelling and redness of the injected paw as well as a strong dose-dependent infiltration of immune cells to the site of injection. Consistent with the neuro-inflammatory signature, mechanical allodynia was decreased in mice lacking Tlr4, as well as in mice treated with minocycline^[5].Vincristine (3mg/kg; iv; 1 time) administrated by a single i.p. injection to mice bearing bilateral subcutaneous xenografts Rh12 or Rh18, induces mean growth delay of >120 and >52day, and repopulating fractions of 0.06% and 5%, respectively^[6].

References:
[1].Jordan MA, Himes RH, Wilson L. Comparison of the effects of vinblastine, Vincristine, vindesine, and vinepidine on microtubule dynamics and cell proliferation in vitro. Cancer Res. 1985 Jun;45(6):2741-7.
[2].Kothari A, Hittelman W N, Chambers T C. Cell cycle–dependent mechanisms underlie Vincristine-induced death of primary acute lymphoblastic leukemia cells[J]. Cancer research, 2016, 76(12): 3553-3561.
[3].Gomez-Deza J, Slavutsky A L, Nebiyou M, et al. Local production of reactive oxygen species drives Vincristine-induced axon degeneration[J]. Cell Death & Disease, 2023, 14(12): 807.
[4].Chao MW, Lai MJ, Liou JP, Chang YL, Wang JC, Pan SL, Teng CM. The synergic effect of Vincristine and vorinostat in leukemia in vitro and in vivo. J Hematol Oncol. 2015 Jul 10;8:82.
[5].Starobova H, Mueller A, Allavena R, et al. Minocycline prevents the development of mechanical allodynia in mouse models of Vincristine-induced peripheral neuropathy[J]. Frontiers in Neuroscience, 2019, 13: 653.
[6].Baguley BC, Holdaway KM, Thomsen LL, Zhuang L, Zwi LJ. Inhibition of growth of colon 38 adenocarcinoma by vinblastine and colchicine: evidence for a vascular mechanism. Eur J Cancer. 1991;27(4):482-7.

Vincristine是一种通过与微管蛋白结合来抑制微管聚合的抑制剂，在无细胞试验中，其IC₅₀值为 32μM。Vincristine还可诱导细胞凋亡^[1]。

Vincristine（100nM；48h）在原代ALL细胞中诱导不同的死亡程序，这取决于细胞周期阶段，G1期细胞容易受到间期微管的干扰^[2]。Vincristine（5nM； 4，8 ，24h）会引发一连串的轴突病变，导致线粒体功能障碍，从而导致轴突ROS水平升高和SARM1依赖性轴突变性^[3]。Vincristine（0.3-10nM；48h）和SAHA对T细胞白血病细胞的作用导致微管动力学发生变化，导致M期停滞，继而诱导细胞凋亡途径^[4]。

Vincristine（1-12 days：<10μg or 0.5mg/kg；12-25 days：10μg； ip； 25d）会导致注射部位的爪子红肿以及免疫细胞的强剂量依赖性浸润。与神经炎症特征相一致的是，缺乏Tlr4的小鼠以及接受米诺环素治疗的小鼠的机械异感减轻^[5]。对携带双侧皮下异种移植Rh12或Rh18的小鼠进行一次静脉注射Vincristine（3mg/kg；iv；一次），可诱导平均生长延迟大于120天和大于52天，再植率分别为0.06%和5%^[6]。