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没食子酸衍生物对氟尿嘧啶和顺铂诱导的血细胞毒性具有细胞保护作用,并能提高乳腺癌动物模型的抗肿瘤活性和生存率。

Anacardic Acids from Confer Cytoprotection against 5-Fluorouracil and Carboplatin Induced Blood Cell Toxicity While Increasing Antitumoral Activity and Survival in an Animal Model of Breast Cancer.

机构信息

Department of Toxicology, Center for Research and Advanced Studies of the National Polytechnic Institute, Ave. IPN 2508, San Pedro Zacatenco, GA Madero, Mexico City 07360, Mexico.

Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala s/n, Santo Tómas, Miguel Hidalgo, Mexico City 11340, Mexico.

出版信息

Molecules. 2021 May 28;26(11):3241. doi: 10.3390/molecules26113241.

Abstract

(cuachalalate) contains anacardic acids (AAs) such as 6-pentadecyl salicylic acid (6SA) that show immunomodulatory and antitumor activity with minimal or no secondary adverse effects. By contrast, most chemotherapeutic agents, such as 5-fluorouracil (5-FU) and carboplatin (CbPt), induce myelosuppression and leukopenia. Here, we investigated the myeloprotective and antineoplastic potential of an AA extract or the 6SA as monotherapy or in combination with commonly used chemotherapeutic agents (5-FU and CbPt) to determine the cytoprotective action of 6SA on immune cells. Treatment of Balb/c breast tumor-bearing female mice with an AA mixture or 6SA did not induce the myelosuppression or leukopenia observed with 5-FU and CbPt. The co-administration of AA mixture or isolated 6SA with 5-FU or CbPt reduced the apoptosis of circulating blood cells and bone marrow cells. Treatment of 4T1 breast tumor-bearing mice with the AA mixture or 6SA reduced tumor growth and lung metastasis and increased the survival rate compared with monotherapies. An increased effect was observed in tumor reduction with the combination of 6SA and CbPt. In conclusion, AAs have important myeloprotective and antineoplastic effects, and they can improve the efficiency of chemotherapeutics, thereby protecting the organism against the toxic effects of drugs such as 5-FU and CbPt.

摘要

(cuachalalate) 含有 6-十五烷基水杨酸(6SA)等庚基安息香酸,具有免疫调节和抗肿瘤活性,且副作用极小或没有。相比之下,大多数化疗药物,如 5-氟尿嘧啶(5-FU)和卡铂(CbPt),会引起骨髓抑制和白细胞减少。在这里,我们研究了 AA 提取物或 6SA 的骨髓保护和抗肿瘤潜力,作为单一疗法或与常用化疗药物(5-FU 和 CbPt)联合使用,以确定 6SA 对免疫细胞的细胞保护作用。用 AA 混合物或 6SA 治疗携带 Balb/c 乳腺癌的雌性小鼠不会引起与 5-FU 和 CbPt 观察到的骨髓抑制或白细胞减少。AA 混合物或分离的 6SA 与 5-FU 或 CbPt 联合给药可减少循环血细胞和骨髓细胞的凋亡。与单一疗法相比,用 AA 混合物或 6SA 治疗 4T1 乳腺癌荷瘤小鼠可减少肿瘤生长和肺转移,并提高存活率。6SA 和 CbPt 的联合使用可观察到肿瘤减少的效果增加。总之,AA 具有重要的骨髓保护和抗肿瘤作用,可提高化疗药物的效率,从而保护机体免受 5-FU 和 CbPt 等药物的毒性作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/718b/8198955/43ee64d1536e/molecules-26-03241-g001.jpg

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