Tunicamycin Mixture is a mixture of homologous nucleoside antibiotics that inhibits N-glycosylation and blocks GlcNAc phosphotransferase (GPT)[1]. Tunicamycin Mixture can induce cellular endoplasmic reticulum (ER) stress and lead to blockage of DNA synthesis and G1 phase arrest [2]. Tunicamycin Mixture inhibits Gram-positive bacteria, yeast, fungi and viruses and has anti-cancer activity [3].
In vitro, pretreatment of RAW264.7 cells with Tunicamycin Mixture (0.5μg/ml) for 2h significantly reduced LPS-induced nitrite production and weakened the expression of iNOS and COX-2 mRNA and protein[4]. Tunicamycin Mixture (1-20μg/ml) treated prostate cancer PC-3 cells for 24-96h, dose-dependently reduced cell viability, blocked the formation of N-glycosylation in proteins and induced endoplasmic reticulum stress [5] .
In vivo, Tunicamycin Mixture (1mg/kg) treated mice via intraperitoneal injection, significantly increased hepatic triglyceride accumulation, inhibited hepatic lipoprotein secretion, and reduced blood glucose levels and liver glycogen content [6]. The administration of a Tunicamycin mixture (2μg) via intratracheal delivery in a neutrophilic asthma model (OVALPS-OVA mice) increased the protein expression levels of endoplasmic reticulum stress markers and inflammatory cytokines, leading to a more severe asthma phenotype in the mice [7].
References:
[1] Hsu J L, Chiang P C, Guh J H. Tunicamycin induces resistance to camptothecin and etoposide in human hepatocellular carcinoma cells: role of cell-cycle arrest and GRP78[J]. Naunyn-Schmiedeberg's archives of pharmacology, 2009, 380: 373-382.
[2] Han C, Jin L, Mei Y, et al. Endoplasmic reticulum stress inhibits cell cycle progression via induction of p27 in melanoma cells[J]. Cellular signalling, 2013, 25(1): 144-149.
[3] Pałasz A, Cież D. In search of uracil derivatives as bioactive agents. Uracils and fused uracils: Synthesis, biological activity and applications[J]. European journal of medicinal chemistry, 2015, 97: 582-611.
[4] Kim S Y, Hwang J S, Han I O. Tunicamycin inhibits Toll-like receptor-activated inflammation in RAW264. 7 cells by suppression of NF-κB and c-Jun activity via a mechanism that is independent of ER-stress and N-glycosylation[J]. European journal of pharmacology, 2013, 721(1-3): 294-300.
[5] Guha P, Kaptan E, Gade P, et al. Tunicamycin induced endoplasmic reticulum stress promotes apoptosis of prostate cancer cells by activating mTORC1[J]. Oncotarget, 2017, 8(40): 68191.
[6] Feng B, Huang X, Jiang D, et al. Endoplasmic reticulum stress inducer tunicamycin alters hepatic energy homeostasis in mice[J]. International journal of molecular sciences, 2017, 18(8): 1710.
[7]Guo Q, Li H, Liu J, et al. Tunicamycin aggravates endoplasmic reticulum stress and airway inflammation via PERK-ATF4-CHOP signaling in a murine model of neutrophilic asthma[J]. Journal of Asthma, 2017, 54(2): 125-133.
Tunicamycin Mixture是一种同源核苷抗生素的混合物, 可抑制N-糖基化并阻断GlcNAc 磷酸转移酶（GPT）[1]。Tunicamycin Mixture可诱导细胞内质网（ER）应激，并导致DNA合成受阻和G1期停滞[2]。Tunicamycin Mixture可抑制革兰氏阳性细菌，酵母，真菌和病毒，并具有抗癌活性[3]。
在体外，Tunicamycin Mixture（0.5μg/ml）预处理RAW264.7细胞2h，显著降低了LPS诱导的亚硝酸盐的产生，并减弱了iNOS和COX-2 mRNA和蛋白质的表达[4]。Tunicamycin Mixture（1-20μg/ml）处理前列腺癌PC-3细胞24-96h，剂量依赖性地降低了细胞活力，阻断蛋白质中N-糖基化的形成并诱导内质网应激[5]。
在体内，Tunicamycin Mixture（1mg/kg）通过腹腔注射处理小鼠，显著增加了肝脏甘油三酯积累，抑制肝脏脂蛋白分泌，降低血糖水平和肝糖原含量[6]。Tunicamycin Mixture（2μg）通过气管内递送治疗中性粒细胞性哮喘模型（OVALPS-OVA小鼠），增加了内质网应激指标和炎症细胞因子的蛋白表达水平，并导致小鼠出现更严重的哮喘表型[7]。