Title:Diallyl Disulfide Inhibits Breast Cancer Stem Cell Progression and Glucose Metabolism by Targeting CD44/PKM2/AMPK Signaling
Volume: 18
Issue: 6
Author(s): Xinhua Xie, Xiaojia Huang, Hailin Tang, Feng Ye, Lu Yang, Xiaofang Guo, Zhi Tian, Xiaofang Xie, Cheng Peng* Xiaoming Xie*
Affiliation:
- School of Pharmacy, Chengdu University of Traditional Chinese Medicine, State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, Sichuan Province and Ministry of Science and Technology, Chengdu,China
- Department 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
Keywords:
Diallyl disulfide, breast cancer stem cell, CD44, PKM2, AMPK, xenograft.
Abstract: 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.
