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Published on: January 26, 2019
Ampelopsins A and C Induce Apoptosis and Metastasis through Downregulating AxL, TYRO3, and FYN Expressions in
Cheng Huang1,2, Yu-Ling Huang3,4, Chia-Chi Wang5
1Department of Biotechnology and Laboratory Science in Medicine , National Yang-Ming University , Taipei 112 , Taiwan.
Abstract:
Ampelopsins A and C are resveratrol oligostilbenes whose role in cancer development remains unknown. This study evaluated the antimetastatic and apoptosis-inducing properties of ampelopsins A and C in MDA-MB-231 cells. The IC50 values of ampelopsins A and C against MDA-MB-231 cells at 72 h were 38.75 ± 4.61 and 2.71 ± 0.21 μM, respectively. However, at 24 h, ampelopsins A and C decreased cell metastasis significantly. Among the 71 proteins present on the human phosphoreceptor tyrosin kinase array, ampelopsin C decreased the phosphorylated protein level of AXL, Dtk (TYRO3), EphA2, EphA6, Fyn, Hck, and SRMS. Additionally, antiproliferation effects of ampelopsin C were enhanced when combined with luteolin and chrysin compared to either two or a single agent in MDA-MB-231 cells. Overall, ampelopsins A and C extracted from Vitis thunbergii are both novel antimetastatic agents and potential therapeutic targets in patients with breast cancer.
Insights
Ampelopsins A and C from Vitis thunbergii show potential as novel antimetastatic agents. These resveratrol oligostilbenes significantly reduced breast cancer cell metastasis and induced apoptosis, suggesting therapeutic value.
Area of Science:
- Phytochemistry
- Cancer Biology
- Pharmacology
Background:
- Resveratrol oligostilbenes, such as ampelopsins A and C, are natural compounds with largely unknown roles in cancer development.
- Breast cancer metastasis remains a significant challenge in oncology, necessitating the identification of novel therapeutic strategies.
Purpose of the Study:
- To evaluate the antimetastatic and apoptosis-inducing properties of ampelopsins A and C in MDA-MB-231 breast cancer cells.
- To investigate the molecular mechanisms underlying the effects of ampelopsins A and C on cancer cell signaling pathways.
Main Methods:
- Cell viability assays (IC50 determination) were performed on MDA-MB-231 cells treated with ampelopsins A and C.
- Cell metastasis assays were conducted at 24 hours post-treatment.
- A human phosphoreceptor tyrosine kinase array was used to analyze protein phosphorylation changes.
- Combination studies with luteolin and chrysin were performed to assess synergistic antiproliferation effects.
Main Results:
- Ampelopsins A and C exhibited varying IC50 values against MDA-MB-231 cells at 72 hours (38.75 ± 4.61 μM and 2.71 ± 0.21 μM, respectively).
- Both compounds significantly decreased MDA-MB-231 cell metastasis at 24 hours.
- Ampelopsin C notably reduced the phosphorylation of key proteins including AXL, TYRO3 (Dtk), EphA2, EphA6, Fyn, Hck, and SRMS.
- The antiproliferation effects of ampelopsin C were potentiated when combined with luteolin and chrysin.
Conclusions:
- Ampelopsins A and C, isolated from Vitis thunbergii, demonstrate significant antimetastatic properties against breast cancer cells.
- These compounds induce apoptosis and modulate critical signaling pathways involved in cancer progression.
- Ampelopsins A and C represent promising novel therapeutic agents and potential targets for breast cancer treatment.
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