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乳酸菌源后生元作为辅助剂在乳腺癌治疗中的应用,以增强包含他莫昔芬和一种新候选药物的常规治疗的抗肿瘤效果:一种氮丙啶-酰肼腙衍生物。

Lactic Acid Bacteria-Derived Postbiotics as Adjunctive Agents in Breast Cancer Treatment to Boost the Antineoplastic Effect of a Conventional Therapeutic Comprising Tamoxifen and a New Drug Candidate: An Aziridine-Hydrazide Hydrazone Derivative.

机构信息

Department of Medical Biochemistry, Medical University of Lodz, 6/8 Mazowiecka Str., 92-215 Lodz, Poland.

Department of Organic and Applied Chemistry, Faculty of Chemistry, University of Lodz, Tamka 12 Str., 91-403 Lodz, Poland.

出版信息

Molecules. 2024 May 13;29(10):2292. doi: 10.3390/molecules29102292.

Abstract

Breast cancer is associated with high mortality and morbidity rates. As about 20-30% of patients exhibiting ER-positive phenotype are resistant to hormonal treatment with the standard drug tamoxifen, finding new therapies is a necessity. Postbiotics, metabolites, and macromolecules isolated from probiotic bacteria cultures have been proven to have sufficient bioactivity to exert prohealth and anticancer effects, making them viable adjunctive agents for the treatment of various neoplasms, including breast cancer. In the current study, postbiotics derived from and cultures were assessed on an in vitro breast cancer model as potential adjunctive agents to therapy utilizing tamoxifen and a candidate aziridine-hydrazide hydrazone derivative drug. Cell viability and cell death processes, including apoptosis, were analyzed for neoplastic MCF-7 cells treated with postbiotics and synthetic compounds. Cell cycle progression and proliferation were analyzed by PI-based flow cytometry and Ki-67 immunostaining. Postbiotics decreased viability and triggered apoptosis in MCF-7, modestly affecting the cell cycle and showing a lack of negative impact on normal cell viability. Moreover, they enhanced the cytotoxic effect of tamoxifen and the new candidate drug toward MCF-7, accelerating apoptosis and the inhibition of proliferation. This illustrates postbiotics' potential as natural adjunctive agents supporting anticancer therapy based on synthetic drugs.

摘要

乳腺癌具有较高的死亡率和发病率。由于约 20-30%表现出 ER 阳性表型的患者对标准药物他莫昔芬的激素治疗具有抗性,因此寻找新的治疗方法是必要的。从益生菌培养物中分离出的后生元、代谢物和大分子已被证明具有足够的生物活性,可发挥促进健康和抗癌作用,使它们成为治疗各种肿瘤(包括乳腺癌)的可行辅助治疗剂。在当前的研究中,评估了 和 培养物的后生元作为辅助治疗剂,与他莫昔芬和候选氮丙啶-酰肼腙衍生物药物联合使用,用于体外乳腺癌模型。用后生元和合成化合物处理的肿瘤 MCF-7 细胞的细胞活力和细胞死亡过程(包括细胞凋亡)进行了分析。通过基于 PI 的流式细胞术和 Ki-67 免疫染色分析细胞周期进程和增殖。后生元降低了 MCF-7 的活力并引发了细胞凋亡,适度影响了细胞周期,并且对正常细胞活力没有负面影响。此外,它们增强了他莫昔芬和新候选药物对 MCF-7 的细胞毒性作用,加速了细胞凋亡和增殖抑制。这说明了后生元作为支持基于合成药物的抗癌治疗的天然辅助治疗剂的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/909e/11124249/f184e0cfe2e7/molecules-29-02292-g001.jpg

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