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桔霉素抗乳腺癌:细胞遗传毒性研究。

Citrinin against breast cancer: A cytogenotoxicological study.

机构信息

Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí - UFPI, Teresina, Piauí, Brazil.

Laboratory of Research in Toxicological Genetics - LAPGENIC, Federal University of Piauí, Teresina, Piauí, Brazil.

出版信息

Phytother Res. 2021 Jan;35(1):504-516. doi: 10.1002/ptr.6830. Epub 2020 Aug 31.

Abstract

Breast cancer is one of the most lethal types of cancer and a leading cause of mortality among Women worldwide. Citrinin (CIT), a polyketide extracted from the fungus Penicillium citrinum, exhibits a wide range of biological activities such as antibacterial, antifungal, and cytotoxic effects. The aim of the current study was to evaluate the antitumoral effects of CIT against 7,12-dimethylbenzanthracene (DMBA)-induced mammary carcinoma in Swiss mice For this, CIT, DMBA and the standard cyclophosphamide (CPA) induced behavioral changes in experimental animals, and these changes were screened by using the rota rod and open field tests. Additionally, hematological, biochemical, immuno-histochemical, and histopathological analyses were carried out. Results suggest that CIT did not alter behavioral, hematological, and biochemical parameters in mice. DMBA induced invasive mammary carcinoma and showed genotoxic effects in the breasts, bone marrow, lymphocytes, and hepatic cells. It also caused mutagenic effects in the formation of micronuclei, bridges, shoots, and binucleate cells in bone marrow and liver. CIT and CPA genotoxic effects were observed after 3 weeks of therapy, where CIT exhibited a repair capacity and induced significant apoptotic damage in mouse lymphocytes. In conclusion, CIT showed antitumoral effects in Swiss mice, possibly through induction of apoptosis.

摘要

乳腺癌是最致命的癌症类型之一,也是全球女性死亡的主要原因之一。桔青霉素(CIT)是从青霉属桔青霉中提取的一种聚酮化合物,具有广泛的生物学活性,如抗菌、抗真菌和细胞毒性作用。本研究旨在评估 CIT 对二甲基苯并蒽(DMBA)诱导的瑞士小鼠乳腺肿瘤的抗肿瘤作用。为此,CIT、DMBA 和标准环磷酰胺(CPA)诱导实验动物的行为改变,并通过转棒和旷场试验筛选这些变化。此外,还进行了血液学、生化、免疫组织化学和组织病理学分析。结果表明,CIT 未改变小鼠的行为、血液学和生化参数。DMBA 诱导侵袭性乳腺肿瘤,并在乳房、骨髓、淋巴细胞和肝细胞中表现出遗传毒性作用。它还在骨髓和肝脏中形成微核、桥、芽和双核细胞中引起诱变作用。CIT 和 CPA 在治疗 3 周后观察到遗传毒性作用,其中 CIT 表现出修复能力,并诱导小鼠淋巴细胞发生显著的凋亡损伤。总之,CIT 对瑞士小鼠表现出抗肿瘤作用,可能是通过诱导细胞凋亡。

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