Britannin, a sesquiterpene lactone, inhibits proliferation and induces apoptosis through the mitochondrial signaling pathway in human breast cancer cells

被引:49
作者
Hamzeloo-Moghadam, Maryam [1 ,5 ]
Aghaei, Mahmoud [2 ]
Fallahian, Faranak [3 ]
Jafari, Seyyed Mehdi [4 ,6 ]
Dolati, Masoumeh [3 ]
Abdolmohammadi, Mohammad Hossein [3 ]
Hajiahmadi, Sima [2 ]
Esmaeili, Somayeh [5 ]
机构
[1] Shahid Beheshti Univ Med Sci, Tradit Med & Mat Med Res Ctr, Tehran, Iran
[2] Isfahan Univ Med Sci, Dept Clin Biochem, Sch Pharm & Pharmaceut Sci, Esfahan, Iran
[3] Qom Univ Med Sci, Cellular & Mol Res Ctr, Qom, Iran
[4] Zahedan Univ Med Sci, Sch Med, Dept Clin Biochem, Zahedan, Iran
[5] Shahid Beheshti Univ Med Sci, Sch Tradit Med, Dept Tradit Pharm, Tehran, Iran
[6] Zahedan Univ Med Sci, Cellular & Mol Res Ctr, Zahedan, Iran
关键词
Sesquiterpene lactone; Britannin; Apoptosis; Breast cancer; MCF-7; MDA-MB-468; PROTEIN-KINASE G; NATURAL-PRODUCTS; DRUG DISCOVERY; DEATH; LINES; P53; INDUCTION; THERAPY; TARGETS; STRESS;
D O I
10.1007/s13277-014-2744-9
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Induction of apoptosis in cancer cells can be a promising treatment method in cancer therapy. Naturally derived products had drawn growing attention as agent in cancer therapy. The main target of anticancer drugs may be distinct, but eventually, they lead to identical cell death pathway, which is apoptosis. Here, we indicated that britannin, a sesquiterpene lactone isolated from Asteraceae family, has antiproliferative activity on the MCF-7 and MDA-MB-468 human breast cancer cells. Annexin V/propidium iodide (PI) staining, Hoechst 33258 staining, and caspase-3/9 activity assay confirmed that britannin is able to induce apoptosis in MCF-7 and MDA-MB-468 cells. The Western blot analysis showed that the expression of Bcl-2 was noticeably decreased in response to britannin treatment, while the expression of Bax protein was increased, which were positively correlated with elevated expression of p53. Moreover, britannin also increased reactive oxygen species (ROS) generation which in turn triggered the loss of mitochondrial transmembrane potential (Delta Im) and the subsequent release of cytochrome c from mitochondria into cytosol. Taken together, these results suggest that britannin inhibits growth of MCF-7 and MDA-MB-468 breast cancer cells through the activation of the mitochondrial apoptotic pathway and may potentially serve as an agent for breast cancer therapy.
引用
收藏
页码:1191 / 1198
页数:8
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