Maackiain suppresses the development of cervical cancer via AMPK priming autophagy
Juan He1,2, Lan Xiang2, Tingting Zhu2
1Department of Obstetrics and Gynecology, First Affiliated Hospital, Anhui Medical University, Hefei, China.
Background:
Maackiain (Mac), a flavonoid analog isolated from Sophora flavescens, exhibits neuroprotective, anti-allergic, anti-inflammatory, and pro-apoptotic effects. It is not clear whether Mac has a therapeutic effect on cervical cancer.
Method:
In this work, we used RT-qPCR, western blot, immunofluorescence, and related methods to detect the therapeutic mechanism of Mac for cervical cancer.
Results:
We demonstrated that Mac significantly inhibited the proliferation, migration, and invasion of human cervical cancer cell lines HeLa and SiHa. And, Mac enhanced the pro-apoptotic effects of cisplatin in treating cervical cancer cells. Mac has shown good efficacy in treating cervical cancer. Furthermore, Mac inhibited the mammalian target of the rapamycin (mTOR) pathway, thereby inducing autophagy in cervical cancer cells. The regulation of mTOR/autophagy pathway by Mac relied on the activation of AMP-activated protein kinase (AMPK), and the inhibition of the AMPK reversed the Mac's anti-cervical cancer activity. In addition, experimental study of Mac in mouse xenograft tumor model further confirmed its good anti-cervical cancer activity.
Conclusion:
Mac inhibits human cervical cancer by activating the AMPK/mTOR/autophagy pathway, indicating that it is a potential natural compound for the treatment of cervical cancer. This study also provides a feasible molecular mechanism for the treatment of cervical cancer.
Insights
Maackiain (Mac) effectively treats cervical cancer by inhibiting cell growth and invasion. It activates the AMPK/mTOR/autophagy pathway, offering a potential natural therapeutic strategy.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Maackiain (Mac), a flavonoid from Sophora flavescens, has known neuroprotective and anti-inflammatory properties.
- Its therapeutic potential in cervical cancer remained unexplored.
Purpose of the Study:
- To investigate the therapeutic effects and molecular mechanisms of Maackiain (Mac) in cervical cancer.
- To evaluate Mac's efficacy alone and in combination with cisplatin.
Main Methods:
- Utilized RT-qPCR, western blot, and immunofluorescence assays.
- Assessed Mac's impact on cervical cancer cell proliferation, migration, and invasion.
- Investigated the role of the AMPK/mTOR/autophagy pathway and conducted in vivo studies using mouse xenograft models.
Main Results:
- Mac significantly inhibited proliferation, migration, and invasion in HeLa and SiHa cervical cancer cell lines.
- Mac enhanced cisplatin's pro-apoptotic effects and demonstrated efficacy in a mouse xenograft model.
- Mac induced autophagy by inhibiting the mammalian target of the rapamycin (mTOR) pathway, mediated by AMP-activated protein kinase (AMPK) activation.
Conclusions:
- Maackiain (Mac) exhibits significant anti-cervical cancer activity by activating the AMPK/mTOR/autophagy pathway.
- Mac represents a promising natural compound for cervical cancer treatment.
- This study elucidates a feasible molecular mechanism for Mac's anti-cancer effects.
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