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MT81 及其结构类似物在艾氏腹水癌荷瘤瑞士白化小鼠体内的抗肿瘤活性。

Antineoplastic activities of MT81 and its structural analogue in Ehrlich ascites carcinoma-bearing Swiss Albino mice.

机构信息

Department of Human Physiology with Community Health, Vidyasagar University, Midnapore, West Bengal India.

出版信息

Oxid Med Cell Longev. 2010 Jan-Feb;3(1):61-70. doi: 10.4161/oxim.3.1.10495.

DOI:10.4161/oxim.3.1.10495
PMID:20716929
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2835890/
Abstract

Many fungal toxins exhibit in vitro and in vivo antineoplastic effects on various cancer cell types. Luteoskyrin,a hydroxyanthraquinone has been proved to be a potent inhibitor against Ehrlich ascites tumor cells. The comparative antitumor activity and antioxidant status of MT81 and its structural analogue [Acetic acid-MT81 (Aa-MT81)] having polyhydroxyanthraquinone structure were assessed against Ehrlich ascites carcinoma (EAC) tumor in mice. The in vitro cytotoxicity was measured by the viability of EAC cells after direct treatment of the said compounds. In in vivo study, MT81 and its structural analogue were administered (i.p.) at the two different doses (5, 7 mg MT81; 8.93, 11.48 mg Aa-MT81/kg body weight) for 7 days after 24 hrs. of tumor inoculation. The activities were assessed using mean survival time (MST), increased life span (ILS), tumor volume, viable tumor cell count, peritoneal cell count, protein percentage and hematological parameters. Antioxidant status was determined by malondialdehyde (MDA) and reduced glutathione (GSH) content, and by the activity of superoxide dismutase (SOD) and catalase (CAT). MT81 and its structural analogues increased the mean survival time, normal peritoneal cell count. They decreased the tumor volume, viable tumor cell count, hemoglobin percentage and packed cell volume. Differential counts of WBC, total counts of RBC & WBC that altered by EAC inoculation, were restored in a dose-dependent manner. Increased MDA and decreased GSH content and reduced activity of SOD, and catalase in EAC bearing mice were returned towards normal after the treatment of MT81 and its structural analogue. Being less toxic than parent toxin MT81, the structural analogue showed more prominent antineoplastic activities against EAC cells compared to MT81. At the same time, both compounds exhibit to some extent antioxidant potential for the EAC-bearing mice.

摘要

许多真菌毒素在体外和体内对各种癌细胞类型表现出抗肿瘤作用。羟基蒽醌 luteoskyrin 已被证明是一种有效的 Ehrlich 腹水肿瘤细胞抑制剂。本研究评估了具有多羟基蒽醌结构的 MT81 及其结构类似物 [乙酸-MT81 (Aa-MT81)] 对艾氏腹水癌 (EAC) 荷瘤小鼠的抗肿瘤活性和抗氧化状态。通过直接处理上述化合物后 EAC 细胞的活力来测量体外细胞毒性。在体内研究中,在接种肿瘤后 24 小时内,以两种不同剂量 (5、7mg MT81;8.93、11.48mg Aa-MT81/kg 体重) 腹腔注射 MT81 和其结构类似物 7 天。使用平均存活时间 (MST)、延长寿命 (ILS)、肿瘤体积、活肿瘤细胞计数、腹腔细胞计数、蛋白百分比和血液学参数评估活性。通过丙二醛 (MDA) 和还原型谷胱甘肽 (GSH) 含量以及超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 的活性来确定抗氧化状态。MT81 和其结构类似物增加了平均存活时间,正常腹腔细胞计数。它们降低了肿瘤体积、活肿瘤细胞计数、血红蛋白百分比和红细胞压积。EAC 接种改变的白细胞分类计数、总红细胞计数和白细胞计数,以剂量依赖的方式得到恢复。MDA 增加、GSH 含量降低、SOD 和 CAT 活性降低在 MT81 和其结构类似物处理后,EAC 荷瘤小鼠的这些指标均恢复正常。与母体毒素 MT81 相比,结构类似物的毒性较小,对 EAC 细胞的抗肿瘤活性比 MT81 更显著。同时,这两种化合物对 EAC 荷瘤小鼠都有一定的抗氧化潜力。

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