Colcemid is a cytoskeletal inhibitor that induces mitotic arrest in the G2/M phase or meiotic arrest in the vesicle rupture (GVBD) phase in mammalian cells or oocytes, respectively[1][2].Colchicine interferes with microtubule polymerization by tightly binding to tubulin dimers and prevents spindle microtubule formation by depolymerization [7].
Cell transformation was observed with doses which were non-cytotoxic and did not cause mitotic inhibition of the cells. Higher dose of colcemid (greater than 0.1 µg/ml) resulted in mitotic inhibition of the cells and a significant loss of colony forming ability, but no increase in the frequency of morphological transformation.A 14-fold increase in the number of aneuploid cells with a near diploid chromosome complement was found in cultures treated with 0.1 µg/ml colcemid and both chromosome loss and gain were induced[4]. Colcemid was more cytotoxic to cells in G2 + M than to G1 + S phase cells, and it slowed the progression of G1 cells to S. These effects of colcemid were much greater in aneuploid B16 melanoma cells than in pseudodiploid Chinese hamster ovary (CHO) cells[5]. Colcemid promotes UVC-induced apoptosis in Chinese hamster ovary cells (CHO.K1).Although colcemid did not affect the excision of UV-induced DNA damages such as photoproducts or cyclobutane pyrimidine dimers, colcemid accumulated the DNA breaks when it was added to cells following UV-irradiation[3].
A mitotic linear accumulation was obtained by continuous colcemid infusion at 5.82 µg/hr. Low dose colcemid infusion (0.582 and 1.455 µg/hr) for 14 hours did not accumulated mitotic cells, but doses more than 5.82 µg/hr of colcemid blocked it completely, accumulating 25.5% of cells after a 20 hours infusion[6].
References:
[1]. Tsuchida T, Yoshimura K, et,al. Colcemid-induced apoptosis of cultured human glioma: electron microscopic and confocal laser microscopic observation of cells sorted in different phases of cell cycle. Cytometry. 1998 Apr 1;31(4):295-9. doi: 10.1002/(sici)1097-0320(19980401)31:43.0.co;2-i. PMID: 9551605.
[2]. Ashley M Rozario, Sam DuwÉ, et,al.Ultra-Low Colcemid Doses Induce Microtubule Dysfunction as Revealed by Super-Resolution Microscopy bioRxiv 2020.08.13.249664; doi:https://doi.org/10.1101/2020.08.13.249664
[3]. Li H, Chang TW, et,al. Colcemid inhibits the rejoining of the nucleotide excision repair of UVC-induced DNA damages in Chinese hamster ovary cells. Mutat Res. 2005 Dec 30;588(2):118-28. doi: 10.1016/j.mrgentox.2005.09.005. Epub 2005 Nov 11. PMID: 16290038.
[4]. Tsutsui T, Maizumi H, et,al. Colcemid-induced neoplastic transformation and aneuploidy in Syrian hamster embryo cells. Carcinogenesis. 1984 Jan;5(1):89-93. doi: 10.1093/carcin/5.1.89. PMID: 6690091.
[5]. Bhuyan BK, Adams EG, et,al. Colcemid effects on B16 melanoma cell progression and aberrant mitotic division. J Cell Physiol. 1987 Aug;132(2):237-45. doi: 10.1002/jcp.1041320207. PMID: 3624316.
[6]. Nomura T. [In vivo cell cycle synchronization of the murine sarcoma 180 by continuous colcemid infusion (author's transl)]. Nihon Seikeigeka Gakkai Zasshi. 1980 Dec;54(12):1719-32. Japanese. PMID: 7288228.
[7]. Rieder CL, Palazzo RE. Colcemid and the mitotic cycle. J Cell Sci. 1992 Jul;102 ( Pt 3):387-92. doi: 10.1242/jcs.102.3.387. PMID: 1506421.
Colcemid是一种细胞骨架抑制剂，可以在哺乳动物细胞或卵母细胞中诱导G2/M期的有丝分裂停滞或囊泡破裂（GVBD）期的减数分裂停滞[1][2]。而秋水仙碱则通过紧密结合到微管蛋白二聚体上干扰微管聚合，并通过去聚合作用阻止纺锤体微管形成[7]。
在非细胞毒性剂量下观察到了细胞转化，这些剂量不会引起细胞有丝分裂抑制。高剂量的科尔塞米德（大于0.1微克/毫升）导致细胞有丝分裂抑制和显著的菌落形成能力损失，但没有增加形态转化频率。用0.1微克/毫升科尔塞米德处理培养物中发现近二倍体染色体组合的非整倍体细胞数量增加了14倍，并诱导染色体缺失和增益。科尔塞米德对G2 + M期的细胞比对G1 + S期的更具有细胞性毒性，并减缓G1期向S期进展。这种影响在非整倍体B16黑色素瘤细胞中比伪二倍体中国仓鼠卵巢（CHO） 细胞更为明显。科尔塞米德促进UVC诱导的中国仓鼠卵巢（CHO.K1） 细胞凋亡。虽然科尔塞米德不影响紫外线诱导DNA损伤如光产物或环戊基嘧啶二聚物的切除，但当它在紫外线照射后加入细胞时，会积累DNA断裂。
通过持续注射5.82微克/小时的科尔赛米德，获得了有丝分裂线性积累。低剂量（0.582和1.455微克/小时）的科尔赛米德注射14个小时并没有积累有丝分裂细胞，但是超过5.82微克/小时的剂量完全阻止了它，并在20个小时的注射后积累了25.5% 的细胞。