Actein induces calcium release in human breast cancer cells
Linda Saxe Einbond1, Jason Mighty2, Stephen Redenti2
1Columbia 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.
Background:
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.
Purpose:
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.
Materials And Methods:
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.
Results:
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.
Conclusions:
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.
Insights
Actein, a compound from black cohosh, inhibits breast cancer cell growth by affecting calcium release and cellular pathways. Nanoparticles enhance its anti-cancer activity, suggesting potential for cancer prevention and treatment.
Area of Science:
- Pharmacology
- Cancer Biology
- Cell Signaling
Background:
- Actein, a triterpene glycoside from black cohosh, exhibits preferential inhibition of breast cancer cell growth and activates the endoplasmic reticulum (ER) stress response.
- The ER IP3 receptor and Na,K-ATPase form a critical signaling microdomain.
- The lipophilic nature of actein may limit its bioavailability and therapeutic efficacy.
Purpose of the Study:
- To develop actein as a potential cancer preventative and therapeutic agent.
- To identify primary molecular targets and effective combinations with chemotherapy.
- To investigate the use of nanoparticles for enhancing actein's anti-cancer activity.
Main Methods:
- Human breast and colon cancer cells, along with 293T and 293T (NF-κB) cells, were treated with actein.
- Cell viability was assessed using MTT assays; signaling pathways were analyzed via luciferase promoter assays and Western blots.
- Calcium release was measured using Fura-2 dye, and actein was conjugated to nanoparticle liposomes to improve bioavailability.
Main Results:
- Actein significantly inhibited human breast cancer cell growth and induced dose-dependent cytoplasmic calcium release, mediated by the ER IP3 receptor.
- The ER IP3 receptor antagonist heparin partially blocked growth inhibition, while the MEK inhibitor U0126 enhanced it.
- Actein demonstrated preferential inhibition of 293T (NF-κB) cells and synergized with thapsigargin; nanoparticle liposomes augmented its growth-inhibitory effects.
Conclusions:
- Actein modulates ER IP3 receptor and Na,K-ATPase activity, leading to calcium release and influencing NF-κB and MEK pathways.
- These findings suggest actein's potential as a therapeutic agent for breast cancer.
- Nanoparticle formulation enhances actein's anti-cancer efficacy, warranting further investigation for clinical applications.
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