The effectiveness of cucurbitacin B in BRCA1 defective breast cancer cells.
The effectiveness of cucurbitacin B in BRCA1 defective breast cancer cells.
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DOI：
10.1371/journal.pone.0055732
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Patmasiriwat P
中科院分区：
文献类型：
--
作者：
Promkan M;Dakeng S;Chakrabarty S;Bögler O;Patmasiriwat P
葫芦素 B (CuB) 是长期抗癌化学预防的潜在药物之一。累积证据表明葫芦素 B 具有强大的细胞生物学活性，例如保肝、抗炎和抗菌作用，但该药物的确切机制尚不清楚。我们研究了从泰国草药 Trichosanthes cucumerina L 中提取的葫芦素 B 对癌细胞的生物学效应。用葫芦素 B 处理野生型 (wt) BRCA1、突变型 BRCA1、BRCA1 敲低和 BRCA1 过表达乳腺癌细胞，并测定对细胞增殖、迁移、侵袭、贴壁依赖性生长的抑制作用。分析处理细胞中 p21/Waf1、p27Kip1 和生存素的基因表达。我们之前的研究表明，BRCA1 表达缺失会导致生存素表达增加，从而导致对紫杉醇敏感性降低。在这项工作中，我们发现葫芦素 B 在细胞增殖、迁移、侵袭和非贴壁依赖性生长方面明显抑制敲低和突变的 BRCA1 乳腺癌细胞，而不是野生型 BRCA1 乳腺癌细胞。此外，强迫细胞过度表达野生型 BRCA1 会显着降低葫芦素 B 对内源突变 BRCA1 细胞生长抑制的效果。有趣的是，葫芦素 B 促进 p21/Waf1 和 p27Kip1 的表达，但抑制 survivin 的表达。我们认为，survivin 可能是 BRCA1 缺陷乳腺癌细胞中葫芦素 B 的重要靶标。
Cucurbitacin B (CuB) is one of the potential agents for long term anticancer chemoprevention. Cumulative evidences has shown that cucurbitacin B provides potent cellular biological activities such as hepatoprotective, anti-inflammatory and antimicrobial effects, but the precise mechanism of this agent is not clearly understood. We examine the biological effects on cancer cells of cucurbitacin B extracted from a Thai herb, Trichosanthes cucumerina L. The wild type (wt) BRCA1, mutant BRCA1, BRCA1 knocked-down and BRCA1 overexpressed breast cancer cells were treated with the cucurbitacin B and determined for the inhibitory effects on the cell proliferation, migration, invasion, anchorage-independent growth. The gene expressions in the treated cells were analyzed for p21/Waf1, p27Kip1 and survivin. Our previous study revealed that loss of BRCA1 expression leads to an increase in survivin expression, which is responsible for a reduction in sensitivity to paclitaxel. In this work, we showed that cucurbitacin B obviously inhibited knocked-down and mutant BRCA1 breast cancer cells rather than the wild type BRCA1 breast cancer cells in regards to the cellular proliferation, migration, invasion and anchorage-independent growth. Furthermore, forcing the cells to overexpress wild type BRCA1 significantly reduced effectiveness of cucurbitacin B on growth inhibition of the endogenous mutant BRCA1 cells. Interestingly, cucurbitacin B promotes the expression of p21/Waf1 and p27Kip1 but inhibit the expression of survivin. We suggest that survivin could be an important target of cucurbitacin B in BRCA1 defective breast cancer cells.
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影响因子：
9.7
作者：
Chan, Kin Tak;Li, Kwan;Xie, Wei Dong
通讯作者：
Xie, Wei Dong
影响因子：
11.5
作者：
Foulkes, WD;Metcalfe, K;Narod, SA
通讯作者：
Narod, SA
影响因子：
5.8
作者：
James, Colin R.;Quinn, Jennifer E.;Harkin, D. Paul
通讯作者：
Harkin, D. Paul
影响因子：
2.7
作者：
FARIAS, MR;SCHENKEL, EP;RUCKER, G
通讯作者：
RUCKER, G
DOI：
10.4137/bcbcr.s8184
发表时间：
2011
期刊：
Breast cancer : basic and clinical research
影响因子：
--
作者：
Atipairin A;Ratanaphan A
通讯作者：
Ratanaphan A