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Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
Diallyl Disulfide Inhibits Breast Cancer Stem Cell Progression and Glucose Metabolism by Targeting CD44/PKM2/AMPK
Xinhua Xie1, Xiaojia Huang1, Hailin Tang1
1Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China.
Background:
It has been reported that diallyl disulfide (DADS) has anti-proliferative activity in many cancers.
Objective:
The purpose of this study was to investigate the functions of DADS and the underlying mechanisms of its effect in breast cancer stem cells (BCSCs).
Method:
Mammosphere formation assay, glucose consumption assay, lactate production assay and mouse xenograft experiments were performed to explore the functions of DADS in BCSCs. ATPase activity assay, western blotting and immunohistochemistry (IHC) assay were conduct to explore the mechanisms underlying the effects of DADS in BCSCs.
Results:
The results showed that DADS suppressed cell stemness and glucose metabolism in BCSCs. In vivo mouse xenograft experiments showed that DADS inhibited the proliferation and metastasis of BCSCs. Then, we continued to explore the mechanisms underlying the effects of DADS in BCSCs and found that DADS acts by targeting CD44, Pyruvate kinase M2 (PKM2) and AMP-activated protein kinase (AMPK) signaling pathways. IHC analysis of 125 breast cancer patients' tissues demonstrated that CD44, PKM2 and AMPK expression levels were positively correlated. In addition, positive CD44, PKM2 and AMPK expression was associated with poor patient overall survival (OS) and disease-free survival (DFS).
Conclusion:
In summary, DADS suppresses cell stemness, proliferation, metastasis and glucose metabolism in BCSCs partly through the inhibition of CD44/PKM2/AMPK. DADS may be used as a potential therapy for breast cancer treatment.
Insights
Diallyl disulfide (DADS) suppresses breast cancer stem cell stemness, proliferation, and metastasis by inhibiting glucose metabolism and targeting CD44, PKM2, and AMPK pathways. DADS shows potential as a breast cancer therapy.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Diallyl disulfide (DADS) exhibits anti-proliferative effects across various cancer types.
- Breast cancer stem cells (BCSCs) are crucial drivers of tumor growth, metastasis, and therapy resistance.
Purpose of the Study:
- To investigate the functional impact of DADS on BCSCs.
- To elucidate the molecular mechanisms underlying DADS's effects in BCSCs.
Main Methods:
- Mammosphere formation, glucose consumption, and lactate production assays were used to assess BCSC function.
- In vivo mouse xenograft models evaluated DADS's anti-proliferative and anti-metastatic effects.
- Western blotting, ATPase activity assays, and immunohistochemistry (IHC) explored DADS's molecular targets and signaling pathways (CD44, PKM2, AMPK).
Main Results:
- DADS significantly suppressed stemness and glucose metabolism in BCSCs.
- In vivo studies demonstrated DADS's inhibition of BCSC proliferation and metastasis.
- DADS targets CD44, Pyruvate Kinase M2 (PKM2), and AMP-activated Protein Kinase (AMPK) signaling pathways.
- High expression of CD44, PKM2, and AMPK correlated with poor patient survival outcomes (OS and DFS).
Conclusions:
- DADS effectively suppresses BCSC stemness, proliferation, metastasis, and glucose metabolism.
- The mechanism involves the inhibition of the CD44/PKM2/AMPK signaling axis.
- DADS presents a promising therapeutic candidate for breast cancer treatment.
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