Targeting breast stem cells with the cancer preventive compounds curcumin and piperine.
Targeting breast stem cells with the cancer preventive compounds curcumin and piperine.
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DOI：
10.1007/s10549-009-0612-x
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发表时间：
2010-08
影响因子：
3.8
通讯作者：
Wicha, Max S.
中科院分区：
文献类型：
--
作者：
Kakarala, Madhuri;Brenner, Dean E.;Korkaya, Hasan;Cheng, Connie;Tazi, Karim;Ginestier, Christophe;Liu, Suling;Dontu, Gabriela;Wicha, Max S.
癌症干细胞假说认为，恶性肿瘤发生在组织干细胞和/或祖细胞通过失调或获得自我更新。为了确定膳食多酚、姜黄素和胡椒碱是否能够调节正常和恶性乳腺干细胞的自我更新，我们研究了这些化合物对乳腺球形成、乳腺干细胞标志物醛脱氢酶（ALDH）表达和Wnt信号传导的影响。在姜黄素、胡椒碱和对照处理后，在通过ALDH阳性选择的未分选的正常乳腺上皮细胞和正常干细胞和早期祖细胞中进行乳腺球形成测定。使用Topflash测定法检查Wnt信号传导。在正常和恶性乳腺细胞中，姜黄素和胡椒碱在5 μ M浓度下抑制乳腺球形成、连续传代和ALDH+细胞百分比达50%，在10 μ M浓度下完全抑制。对细胞分化无影响。姜黄素和胡椒碱在5 μ M时抑制Wnt信号传导50%，在10 μ M时完全抑制。姜黄素和胡椒碱单独和组合抑制乳腺干细胞自我更新，但不会对分化细胞造成毒性。这些化合物可能是潜在的癌症预防剂。乳腺球形成测定可以是评估癌症预防剂功效的可定量生物标志物，Wnt信号传导评估是用于人类临床试验的机制生物标志物。
The cancer stem cell hypothesis asserts that malignancies arise in tissue stem and/or progenitor cells through the dysregulation or acquisition of self-renewal. In order to determine whether the dietary polyphenols, curcumin and piperine, are able to modulate the self-renewal of normal and malignant breast stem cells, we examined the effects of these compounds on mammosphere formation, on expression of the breast stem cell marker aldehyde dehydrogenase (ALDH), and on Wnt signaling. Mammosphere formation assays were performed after curcumin, piperine and control treatment in unsorted normal breast epithelial cells and normal stem and early progenitor cells, selected by ALDH positivity. Wnt signaling was examined using a Topflash assay. Both curcumin and piperine inhibited mammosphere formation, serial passaging and percent of ALDH+ cells, by 50% at 5 μM and completely at 10 μM concentration in normal and malignant breast cells. There was no effect on cellular differentiation. Wnt signaling was inhibited by both curcumin and piperine by 50% at 5 μM and completely at 10μM. Curcumin and piperine separately, and in combination, inhibit breast stem cell self renewal but do not cause toxicity to differentiated cells. These compounds could be potential cancer preventive agents. Mammosphere formation assays may be a quantifiable biomarker to assess cancer preventive agent efficacy and Wnt signaling assessment a mechanistic biomarker for use in human clinical trials.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
通讯作者：
Wicha, MS
影响因子：
4.3
作者：
Limtrakul, Pornngarm;Chearwae, Wanida;Ambudkar, Suresh V.
通讯作者：
Ambudkar, Suresh V.
影响因子：
--
作者：
Lao, Christopher D;Ruffin, Mack T 4th;Brenner, Dean E
通讯作者：
Brenner, Dean E
影响因子：
5.8
作者：
Anuchapreeda, S;Leechanachai, P;Limtrakul, P
通讯作者：
Limtrakul, P
影响因子：
5.8
作者：
Aggarwal, Bharat B.;Banerjee, Sanjeev;Sethi, Gautam
通讯作者：
Sethi, Gautam