Columbia University College of Physicians and Surgeons, New York, NY 10032, USA; Lehman College, CUNY, Bronx, NY 10468, USA; The New York Botanical Garden, New York, NY 10458, USA.
Lehman College, CUNY, Bronx, NY 10468, USA.
Fitoterapia. 2013 Dec;91:28-38. doi: 10.1016/j.fitote.2013.07.025. Epub 2013 Aug 9.
The triterpene glycoside actein from the herb black cohosh preferentially inhibits the growth of breast cancer cells and activates the ER stress response. The ER IP3 receptor and Na,K-ATPase form a signaling microdomain. Since actein is lipophilic, its action may be limited by bioavailability.
To develop actein to prevent and treat cancer, we examined the primary targets and combinations with chemotherapy agents, as well as the ability of nanoparticles to enhance the activity.
To reveal signaling pathways, we treated human breast and colon cancer, as well as 293T and 293T (NF-κB), cells with actein, and measured effects using the MTT, luciferase promoter, Western blot and histology assays. To assess effects on calcium release, we preloaded cells with the calcium sensitive dye Fura-2. To enhance bioavailability, we conjugated actein to nanoparticle liposomes.
Actein strongly inhibited the growth of human breast cancer cells and induced a dose dependent release of calcium into the cytoplasm. The ER IP3 receptor antagonist heparin blocked this release, indicating that the receptor is required for activity. Heparin partially blocked the growth inhibitory effect, while the MEK inhibitor U0126 enhanced it. Consistent with this, actein synergized with the ER mobilizer thapsigargin. Further, actein preferentially inhibited the growth of 293T (NF-κB) cells. Nanoparticle liposomes increased the growth inhibitory activity of actein.
Actein alters the activity of the ER IP3 receptor and Na,K-ATPase, induces calcium release and modulates the NF-κB and MEK pathways and may be worthwhile to explore to prevent and treat breast cancer.
黑升麻中的三萜糖苷 Actein 优先抑制乳腺癌细胞的生长并激活 ER 应激反应。内质网 IP3 受体和 Na，K-ATP 酶形成一个信号微区。由于 Actein 具有亲脂性，其作用可能受到生物利用度的限制。
为了开发 Actein 来预防和治疗癌症，我们研究了其主要靶点和与化疗药物的联合作用，以及纳米颗粒增强其活性的能力。
为了揭示信号通路，我们用 Actein 处理人乳腺癌和结肠癌细胞以及 293T 和 293T（NF-κB）细胞，并通过 MTT、荧光素酶启动子、Western blot 和组织学检测来测量其效果。为了评估对钙释放的影响，我们用钙敏感染料 Fura-2 预加载细胞。为了增强生物利用度，我们将 Actein 与纳米颗粒脂质体偶联。
Actein 强烈抑制人乳腺癌细胞的生长并诱导细胞质中钙的剂量依赖性释放。内质网 IP3 受体拮抗剂肝素阻断了这种释放，表明该受体是活性所必需的。肝素部分阻断了生长抑制作用，而 MEK 抑制剂 U0126 增强了该作用。与此一致的是，Actein 与 ER 动员剂 Thapsigargin 协同作用。此外，Actein 优先抑制 293T（NF-κB）细胞的生长。纳米颗粒脂质体增加了 Actein 的生长抑制活性。
Actein 改变内质网 IP3 受体和 Na，K-ATP 酶的活性，诱导钙释放，并调节 NF-κB 和 MEK 途径，可能值得探索用于预防和治疗乳腺癌。
