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苦叶花椒胶乳蛋白对肉瘤 180 的体内生长抑制作用。

In vivo growth inhibition of sarcoma 180 by latex proteins from Calotropis procera.

机构信息

Departamento de Bioquímica e Biologia Molecular, Universidade Federal do Ceará, Campus do Pici, Caixa Postal 6033, 60.451-970, Fortaleza, Ceará, Brazil.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2010 Aug;382(2):139-49. doi: 10.1007/s00210-010-0525-6. Epub 2010 Jun 3.

Abstract

Latex of Calotropis procera has been described as a relevant source of pharmacologically active proteins, including proteins with anticancer activity. A previous in vitro study of laticifer proteins (LP) from C. procera reported that they had selective cytotoxic effects on human cancer cell lines. The aim of this study was to determine the effects of LP in vivo using mice transplanted with sarcoma 180. Biochemical, hematological, histopathological, and morphological analyses were performed in animals given LP by oral or intraperitoneal routes. LP significantly reduced tumor growth (51.83%) and augmented the survival time of animals for up to 4 days. Tumor growth inhibitory activity was lost when LP fraction was submitted to proteolysis, acidic treatment, or pretreated with iodoacetamide. However, LP retained its inhibitory activities on sarcoma 180 growth after heat treatment. Thus, it seems that heat-stable proteins are involved in tumor suppression. Biochemical parameters, such as the enzymatic activity of aspartate aminotransferase and alanine aminotransferase and urea content in serum were not affected in treated mice. It is worth noting that LP completely eliminated the 5-FU-induced depletion of leukocytes in mice even when given orally. The active proteins were recovered in a single fraction by ion exchange chromatography and still exhibited anticancer activity. This study confirms the pharmacological potential of proteins from the latex of C. procera to control sarcoma cell proliferation.

摘要

麻疯树乳胶被描述为具有药理活性的蛋白质的相关来源,包括具有抗癌活性的蛋白质。先前对麻疯树乳汁蛋白(LP)的体外研究表明,它们对人癌细胞系具有选择性细胞毒性作用。本研究旨在使用移植肉瘤 180 的小鼠体内测定 LP 的作用。通过口服或腹腔内途径给予 LP 的动物进行了生化、血液学、组织病理学和形态学分析。LP 显著抑制肿瘤生长(51.83%),并将动物的存活时间延长至 4 天。当 LP 被蛋白酶解、酸性处理或用碘乙酰胺预处理时,肿瘤生长抑制活性丧失。然而,LP 在热处理后仍保留对肉瘤 180 生长的抑制活性。因此,似乎热稳定蛋白参与肿瘤抑制。处理小鼠的血清中天冬氨酸氨基转移酶和丙氨酸氨基转移酶的酶活性以及尿素含量等生化参数不受影响。值得注意的是,LP 即使口服给药也能完全消除 5-FU 诱导的小鼠白细胞减少。活性蛋白通过离子交换色谱在单个馏分中回收,仍然表现出抗癌活性。这项研究证实了麻疯树乳胶中蛋白质控制肉瘤细胞增殖的药理学潜力。

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