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阿萨伊提取物与抗癌药物联合使用可增强乳腺癌模型MCF-10A细胞的协同毒性并诱导其凋亡。

Açaí extract and anticancer drug combination promotes synergistic toxicity and apoptosis in MCF-10A cells of breast cancer model.

作者信息

Thornton Destini, Heck Kabre, Patrick Madison, Kromtit Rinbam, Benedict Chloe, Pondugula Satyanarayana R, Shen Jianzhong, Calderón Angela I

机构信息

Department of Drug Discovery and Development, Harrison College of Pharmacy, Auburn University, Auburn AL, 36849, USA.

Department of Clinical Sciences, Florida State University College of Medicine, Tallahassee, FL, 32304, USA.

出版信息

J Ethnopharmacol. 2025 Sep 25;353(Pt A):120361. doi: 10.1016/j.jep.2025.120361. Epub 2025 Aug 6.

Abstract

AIM OF THE STUDY

To evaluate the toxicological potential between açaí extracts and two widely used anticancer drugs - methotrexate and tamoxifen.

MATERIALS AND METHODS

Euterpe oleracea Mart. fruit powder extracts obtained from a name brand company in Brazil and two açaí dietary supplement brands were tested on two cancer cell lines, MCF-7 and MDA-MB-231, and one normal epithelial breast cell line, MCF-10A. Cell viability was measured using MTT assay. The data was analyzed using SynergyFinder Plus and Compusyn to determine the potential synergism, antagonism, or additive effect of the açaí extract when combined with the selected anticancer drugs, tamoxifen and methotrexate.

RESULTS

When combined with methotrexate, the methanol extract of the açaí powder and the acidic methanol extract of the açaí dietary supplements caused significant synergy (potentiation), thus increasing toxicity, of the combination to the normal cell line, MCF-10A. The combination of the acidic methanol extract of the açaí dietary supplements also induced apoptosis with the MCF-10A cells. Methotrexate was potentiated by the aqueous extract of the açaí powder when tested with the MCF-7 cells. Tamoxifen toxicity was increased only with the MCF-7 cells. Pre-exposure of the MCF-10A cells to the methanol extract of the açaí powder caused increased tamoxifen toxicity for the normal cell line but decreased toxicity for methotrexate combination. There were no significant indications of the açaí extracts causing an antagonistic relationship with either anticancer drug.

CONCLUSION

The açaí extracts evaluated here potentiated both anticancer drugs, increasing their toxicity for all cell lines with the most significant increase in toxicity occurring with normal cell line, MCF-10A. The toxicity was further confirmed to be through induction of apoptosis. This calls for further investigation of the chemical constituents of açaí that are the cause of the toxicity of the combination of anticancer drug and açaí extract.

摘要

研究目的

评估阿萨伊提取物与两种广泛使用的抗癌药物——甲氨蝶呤和他莫昔芬之间的毒理学潜力。

材料与方法

从巴西一家知名公司获得的巴西莓果实粉末提取物以及两个阿萨伊膳食补充剂品牌,在两种癌细胞系MCF - 7和MDA - MB - 231以及一种正常乳腺上皮细胞系MCF - 10A上进行测试。使用MTT法测量细胞活力。使用SynergyFinder Plus和Compusyn分析数据,以确定阿萨伊提取物与所选抗癌药物他莫昔芬和甲氨蝶呤联合使用时的潜在协同、拮抗或相加作用。

结果

当与甲氨蝶呤联合使用时,阿萨伊粉末的甲醇提取物和阿萨伊膳食补充剂的酸性甲醇提取物对正常细胞系MCF - 10A产生显著的协同作用(增强作用),从而增加了联合用药的毒性。阿萨伊膳食补充剂的酸性甲醇提取物与MCF - 10A细胞联合使用时也诱导了细胞凋亡。用MCF - 7细胞测试时,阿萨伊粉末的水提取物增强了甲氨蝶呤的作用。仅在MCF - 7细胞中,他莫昔芬的毒性增加。MCF - 10A细胞预先暴露于阿萨伊粉末的甲醇提取物会导致正常细胞系对他莫昔芬的毒性增加,但对甲氨蝶呤联合用药的毒性降低。没有明显迹象表明阿萨伊提取物与任何一种抗癌药物存在拮抗关系。

结论

此处评估的阿萨伊提取物增强了两种抗癌药物的作用,增加了它们对所有细胞系的毒性,其中对正常细胞系MCF - 10A的毒性增加最为显著。毒性进一步证实是通过诱导细胞凋亡。这需要进一步研究阿萨伊中导致抗癌药物与阿萨伊提取物联合用药毒性的化学成分。

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