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Marine-Derived Stichloroside C2 Inhibits Epithelial-Mesenchymal Transition and Induces Apoptosis through the
Chuang Cui1,2, Chen-Huan Ding3, Fang-Fang Liu4
1Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Background:
Triterpenoid saponins from sea cucumbers exhibit significant antitumour, antifungal, and antibacterial activities. However, the associated molecular mechanisms have yet to be elucidated. In this study, we screened and explored the antitumour activity and underlying mechanisms of triterpenoid saponins isolated from Thelenota ananas.
Methods:
We isolated and purified sea cucumber saponins, determined their chemical structures, and confirmed their function in vitro. We also screened and explored the antitumour activity and underlying mechanisms of triterpenoid saponins isolated from Thelenota ananas.
Results:
Four saponins were discovered from sea cucumber Thelenota ananas collected from the South China Sea. We found that stichloroside C2 (STC2) inhibited the proliferation and clonogenesis of the human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and mouse TNBC cell line 4 T1 in a dose-dependent manner and induced apoptosis and cycle arrest in these two TNBC cell lines. STC2 induced DNA damage in two TNBC cell lines and significantly increased the protein expression level of the DNA double-strand break marker γ-H2AX. STC2 downregulated the protein expression levels of phosphorylated cyclin-dependent kinase 1 (CDK1), cyclin B1, CDK2, and cyclin A2 in MDA-MB-231 and 4 T1 cells. STC2 upregulated Bax and cleaved PARP protein expression in two types of breast cancer cells. In addition, STC2 promoted E-cadherin expression; inhibited vimentin expression; upregulated the phosphorylation levels of the mitogen-activated protein kinase (MAPK) signalling pathway-related proteins p38, JNK, and ERK1/2; and downregulated Akt phosphorylation.
Conclusions:
STC2 exerts anti-TNBC activity, inhibits epithelial-mesenchymal transition (EMT), and induces apoptosis by regulating the cell cycle, EMT-related proteins, and MAPK signalling pathway.
Insights
Sea cucumber saponin stichloroside C2 (STC2) shows potent anti-cancer effects against triple-negative breast cancer (TNBC) by inducing cell death and halting cell division. This study elucidates STC2
Area of Science:
- Marine Natural Products Chemistry
- Cancer Biology
- Pharmacology
Background:
- Triterpenoid saponins from sea cucumbers possess known antitumour properties.
- The specific molecular mechanisms of these compounds remain largely uncharacterized.
- This study focuses on saponins from *Thelenota ananas*.
Purpose of the Study:
- To investigate the antitumour activity of triterpenoid saponins isolated from *Thelenota ananas*.
- To elucidate the underlying molecular mechanisms of action.
- To evaluate the potential of these compounds as therapeutic agents for triple-negative breast cancer (TNBC).
Main Methods:
- Isolation and purification of saponins from *Thelenota ananas*.
- Determination of chemical structures.
- In vitro functional assays using human (MDA-MB-231) and mouse (4T1) TNBC cell lines.
- Analysis of apoptosis, cell cycle, DNA damage, and key protein expression levels (e.g., γ-H2AX, cell cycle regulators, EMT markers, MAPK/Akt pathways).
Main Results:
- Four saponins were identified; stichloroside C2 (STC2) demonstrated significant inhibition of TNBC cell proliferation and clonogenesis.
- STC2 induced apoptosis and cell cycle arrest in MDA-MB-231 and 4T1 cells.
- STC2 caused DNA damage, altered expression of cell cycle and apoptosis-related proteins, inhibited epithelial-mesenchymal transition (EMT), and modulated MAPK and Akt signaling pathways.
Conclusions:
- Stichloroside C2 (STC2) exhibits significant anti-TNBC activity.
- STC2 functions by inducing apoptosis, regulating the cell cycle, and inhibiting EMT.
- The compound modulates key signaling pathways including MAPK and Akt, offering a potential therapeutic strategy.
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