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多苞菊对LA7诱导的大鼠乳腺癌的化学预防作用及一种细胞毒性倍半萜内酯对MCF7细胞的凋亡作用:一种生物测定指导的方法。

The Chemopreventive Effect of Tanacetum Polycephalum Against LA7-Induced Breast Cancer in Rats and the Apoptotic Effect of a Cytotoxic Sesquiterpene Lactone in MCF7 Cells: A Bioassay-Guided Approach.

作者信息

Karimian Hamed, Fadaeinasab Mehran, Moghadamtousi Soheil Zorofchian, Hajrezaei Maryam, Zahedifard Maryam, Razavi Mahboubeh, Safi Sher Zaman, Mohan Syam, Khalifa Shaden A M, El-Seedi Hesham R, Abdulla Mahmood Amin, Ali Hapipah Mohd, Noordin Mohamad Ibrahim

机构信息

Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.

出版信息

Cell Physiol Biochem. 2015;36(3):988-1003. doi: 10.1159/000430273. Epub 2015 Jun 15.

Abstract

BACKGROUND

Tanacetum polycephalum L. Schultz-Bip is a member of the Asteraceae family. This study evaluated the chemopreventive effect of a T. polycephalum hexane extract (TPHE) using in in vivo and in vitro models.

METHODS AND RESULTS

Five groups of rats: normal control, cancer control, TPHE low dose, TPHE high dose and positive control (tamoxifen) were used for the in vivo study. Histopathological examination showed that TPHE significantly suppressed the carcinogenic effect of LA7 tumour cells. The tumour sections from TPHE-treated rats demonstrated significantly reduced expression of Ki67 and PCNA compared to the cancer control group. Using a bioassay-guided approach, the cytotoxic compound of TPHE was identified as a tricyclic sesquiterpene lactone, namely, 8β- hydroxyl- 4β, 15- dihydrozaluzanin C (HDZC). Signs of early and late apoptosis were observed in MCF7 cells treated with HDZC and were attributed to the mitochondrial intrinsic pathway based on the up-regulation of Bax and the down-regulation of Bcl-2. HDZC induced cell cycle arrest in MCF7 cells and increased the expression of p21 and p27 at the mRNA and protein levels.

CONCLUSION

This results of this study substantiate the anticancer effect of TPHE and highlight the involvement of HDZC as one of the contributing compounds that act by initiating mitochondrial-mediated apoptosis.

摘要

背景

多苞菊(Tanacetum polycephalum L. Schultz - Bip)是菊科植物。本研究使用体内和体外模型评估了多苞菊己烷提取物(TPHE)的化学预防作用。

方法与结果

体内研究使用了五组大鼠:正常对照组、癌症对照组、TPHE低剂量组、TPHE高剂量组和阳性对照组(他莫昔芬)。组织病理学检查表明,TPHE显著抑制了LA7肿瘤细胞的致癌作用。与癌症对照组相比,TPHE处理的大鼠肿瘤切片显示Ki67和PCNA的表达显著降低。采用生物测定指导方法,确定TPHE的细胞毒性化合物为三环倍半萜内酯,即8β - 羟基 - 4β, 15 - 二氢扎鲁扎宁C(HDZC)。在用HDZC处理的MCF7细胞中观察到早期和晚期凋亡迹象,基于Bax的上调和Bcl - 2的下调,这些凋亡迹象归因于线粒体内在途径。HDZC诱导MCF7细胞的细胞周期停滞,并在mRNA和蛋白质水平上增加p21和p27的表达。

结论

本研究结果证实了TPHE的抗癌作用,并突出了HDZC作为通过启动线粒体介导的凋亡发挥作用的一种促成化合物的参与。

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