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波多黎各金合欢通过改变 Bax/Bcl-2 比值和前列腺 LNCaP 细胞生长停滞表现出抗癌作用。

Calliandra portoricensis Benth exhibits anticancer effects via alteration of Bax/Bcl-2 ratio and growth arrest in prostate LNCaP cells.

机构信息

Laboratories for Biomembrane Research and Biotechnology, Department of Biochemistry, College of Medicine, University of Ibadan, Ibadan, Nigeria; School of Chemistry and Biochemistry, Parker H. Petit for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.

Cancer Research and Molecular Biology Laboratory, Department of Biochemistry, University of Ibadan, Nigeria.

出版信息

J Ethnopharmacol. 2019 Apr 6;233:64-72. doi: 10.1016/j.jep.2018.12.020. Epub 2018 Dec 21.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Apoptosis is downregulated in all forms of cancers. The mitochondrion has been implicated in the apoptotic process and, recently has been targeted in cancer therapy because of its role in cancer progression. Medicinal plants are used in the treatment of cancer, in particular, Calliandra portoricensis (CP) in the management of prostate cancer in Nigeria ethnomedicine.

AIM OF THE STUDY

This study was designed to investigate the effects of CP on mitochondrial-mediated apoptosis and cell proliferation using prostate cancer cells.

MATERIALS AND METHODS

Prostatic LNCaP, DU-145, lung adenocarcinoma and healthy VERO cells were used to assess cell proliferation. Cell cycle analysis was evaluated by flow cytometry. Levels of pro-apoptotic Bax, anti-apoptotic Bcl-2, Cytochrome C Release (CCR) and activation of caspases 3(C3) and 9 (C9) were determined by ELISA, while mitochondrial integrity was evaluated by Fluorescent Intensity Ratio (FIR).

RESULTS

Methanol Fraction of C. portoricensis (MFCP) inhibited proliferation of prostatic LNCaP, DU-145, lung adenocarcinoma and healthy VERO cells with IC values of 2.4 ± 0.2, 3.3 ± 0.2, 3.6 ± 0.2 and 17.9 ± 1.6 µg/mL, respectively. The growth inhibition by MFCP correlated with a 3-fold decreased expression of Bcl-2 and a 4-fold increase in Bax levels at 10 µg/mL in LNCaP cells. Furthermore, MFCP caused a 3.5-fold reduction in FIR at 10 µg/mL and induced CCR by 4.2 folds at the same concentration relative to control. The MFCP-induced CCR is associated with activation of C3 and C9 at 10 µg/mL by 4.2 and 5.1 folds, respectively which prompted cancer cells to arrest at S phase. The LC-MS analysis revealed the presence of polyphenols including gallic acid and afzelechin in MFCP.

CONCLUSION

Taken together, MFCP- induced cell death is mediated by alteration of mitochondrial integrity and cell cycle arrest. Hence, methanol fraction of C. portoricensis may be effective for cancer pharmacotherapy.

摘要

民族药理学相关性

细胞凋亡在所有形式的癌症中都受到抑制。线粒体已被牵连到凋亡过程中,并且由于其在癌症进展中的作用,最近已成为癌症治疗的靶点。药用植物被用于治疗癌症,特别是在尼日利亚民族医学中用于治疗前列腺癌的 Calliandra portoricensis (CP)。

研究目的

本研究旨在使用前列腺癌细胞研究 CP 对线粒体介导的细胞凋亡和细胞增殖的影响。

材料和方法

使用前列腺 LNCaP、DU-145、肺腺癌和健康 VERO 细胞来评估细胞增殖。通过流式细胞术评估细胞周期分析。通过 ELISA 测定促凋亡 Bax、抗凋亡 Bcl-2、细胞色素 C 释放 (CCR) 和 caspase 3(C3) 和 9 (C9) 的激活水平,而通过荧光强度比 (FIR) 评估线粒体完整性。

结果

C. portoricensis 的甲醇部分 (MFCP) 抑制前列腺 LNCaP、DU-145、肺腺癌和健康 VERO 细胞的增殖,IC 值分别为 2.4 ± 0.2、3.3 ± 0.2、3.6 ± 0.2 和 17.9 ± 1.6 µg/mL。MFCP 的生长抑制与 LNCaP 细胞中 Bcl-2 的表达降低 3 倍和 Bax 水平增加 4 倍相关。此外,MFCP 在 10 µg/mL 时使 FIR 降低 3.5 倍,并在相同浓度下引起 CCR 增加 4.2 倍。MFCP 诱导的 CCR 与 C3 和 C9 的激活相关,在 10 µg/mL 时分别增加 4.2 倍和 5.1 倍,这促使癌细胞在 S 期停滞。LC-MS 分析表明 MFCP 中存在多酚,包括没食子酸和阿夫泽林。

结论

综上所述,MFCP 诱导的细胞死亡是通过改变线粒体完整性和细胞周期停滞介导的。因此,C. portoricensis 的甲醇部分可能对癌症化疗有效。

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