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H. Lév. 叶提取物通过抑制 MAPK 通路抑制 MDA-MB-231 乳腺癌细胞增殖并诱导细胞凋亡。

H. Lév. Leaf Extract Inhibits the Proliferation of MDA-MB-231 Breast Cancer Cells and Induces Apoptosis the MAPK Pathway and .

机构信息

Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, Republic of Korea.

DPBioPharm, Namyangju, Republic of Korea.

出版信息

Anticancer Res. 2023 Jul;43(7):3047-3056. doi: 10.21873/anticanres.16476.

Abstract

BACKGROUND/AIM: The toxic side effects of therapies against breast cancer can affect the quality of life of patients, necessitating the use of naturally-derived therapeutics. Here, we investigated the effects of Dendropanax morbiferus H. Lév. leaf (DPL) extract on breast cancer cells in vitro and in vivo to assess its anticancer potential.

MATERIALS AND METHODS

MDA-MB-231 breast cancer cells were treated with DPL, and the in vitro effect of DPL on the cells was evaluated through an MTT assay, DAPI staining, annexin V/propidium iodide double staining, and western blotting. The in vivo effects of DPL were measured through the MDA-MB-231 tumor xenograft mouse model. A TUNEL assay and immunohistochemistry were used to determine the extent of apoptosis and p-p38 expression in tumor tissues, respectively.

RESULTS

DPL treatment significantly suppressed cell viability in a concentration-dependent manner. Furthermore, DPL treatment resulted in increased apoptotic body formation, apoptosis rate, cleaved poly (ADP-ribose) polymerase and B-cell lymphoma 2 (Bcl-2)-associated X protein levels, phosphorylation of mitogen-activated protein kinase (MAPK) pathway proteins, and decreased Bcl-2 levels. In addition, the antitumor effect in vivo was confirmed through the xenograft model, where decreased tumor volume and weight following DPL administration were observed. Further, apoptosis and increased p-p38 levels in tumor tissues were observed, and no pathological abnormalities were found in the liver or kidney.

CONCLUSION

DPL inhibits proliferation through MAPK-mediated apoptosis in breast cancer cells and tumors, suggesting the potential of DPL as a natural therapeutic agent for breast cancer.

摘要

背景/目的:乳腺癌治疗的毒副作用会影响患者的生活质量,因此需要使用天然来源的治疗药物。本研究旨在探讨五加科鹅掌柴(Dendropanax morbiferus H. Lév.)叶提取物(DPL)对体外和体内乳腺癌细胞的作用,评估其抗癌潜力。

材料和方法

用 DPL 处理 MDA-MB-231 乳腺癌细胞,通过 MTT 测定、DAPI 染色、膜联蛋白 V/碘化丙啶(PI)双染和 Western blot 评估 DPL 对细胞的体外作用。通过 MDA-MB-231 肿瘤异种移植小鼠模型测量 DPL 的体内作用。TUNEL 检测和免疫组织化学分别用于确定肿瘤组织中细胞凋亡和磷酸化 p38 表达的程度。

结果

DPL 处理以浓度依赖性方式显著抑制细胞活力。此外,DPL 处理导致凋亡小体形成增加、凋亡率增加、多聚(ADP-核糖)聚合酶和 B 细胞淋巴瘤 2(Bcl-2)相关 X 蛋白水平降低、丝裂原活化蛋白激酶(MAPK)途径蛋白磷酸化增加以及 Bcl-2 水平降低。此外,通过异种移植模型证实了 DPL 的体内抗肿瘤作用,其中 DPL 给药后肿瘤体积和重量均减少。此外,在肿瘤组织中观察到细胞凋亡增加和 p-p38 水平升高,且肝脏或肾脏未发现病理异常。

结论

DPL 通过 MAPK 介导的凋亡抑制乳腺癌细胞和肿瘤的增殖,表明 DPL 作为乳腺癌天然治疗药物具有潜力。

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