Title:Berberine Exerts Anti-cancer Activity by Modulating Adenosine Monophosphate- Activated Protein Kinase (AMPK) and the Phosphatidylinositol 3-Kinase/ Protein Kinase B (PI3K/AKT) Signaling Pathways
Volume: 27
Issue: 4
Author(s): Jin Huang, Wei Feng, Shanshan Li, Huiling Tang, Siru Qin, Wei Li, Yinan Gong, Yuxin Fang, Yangyang Liu, Shenjun Wang, Yi Guo, Zhifang Xu*Qian Shen*
Affiliation:
- Research Center of Experimental Acupuncture Science, Tianjin University of Traditional Chinese Medicine, Tianjin 301617,China
- Department of Massage and Physiotherapy, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing 100078,China
Keywords:
Berberine, anti-cancer, AMPK, PI3K/AKT, mechanism, rhizoma coptidis.
Abstract:
Background: The antagonistic relationship between adenosine monophosphate-activated protein kinase
(AMPK) and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signaling play a vital role in cancer
development. The anti-cancer effects of berberine have been reported as a main component of the traditional
Chinese medicine Rhizoma coptidis, although the roles of these signaling pathways in these effects have not
been systematically reviewed.
Methods: We searched the PubMed database for studies with keywords including [“berberine”] and [“tumor”
or “cancer”] and [“AMPK”] or [“AKT”] published between January 2010 and July 2020, to elucidate the roles
of the AMPK and PI3K/AKT pathways and their upstream and downstream targets in the anti-cancer effects of
berberine.
Results: The anti-cancer effects of berberine include inhibition of cancer cell proliferation, promotion of apoptosis
and autophagy in cancer cells, and prevention of metastasis and angiogenesis. The mechanism of these effects
involves multiple cell kinases and signaling pathways, including activation of AMPK and forkhead box
transcription factor O3a (FOXO3a), accumulation of reactive oxygen species (ROS), and inhibition of the activity
of PI3K/AKT, rapamycin (mTOR) and nuclear factor-κB (NF-κB). Most of these mechanisms converge on
regulation of the balance of AMPK and PI3K/AKT signaling by berberine.
Conclusion: This evidence supports the possibility that berberine is a promising anti-cancer natural product,
with pharmaceutical potential in inhibiting cancer growth, metastasis and angiogenesis via multiple pathways,
particularly by regulating the balance of AMPK and PI3K/AKT signaling. However, systematic preclinical
studies are still required to provide scientific evidence for further clinical studies.
