Title:The Use of Naphthoquinones and Furano-naphthoquinones as Antiinvasive Agents
Volume: 25
Issue: 38
Author(s): Nga Yi Tsang, Wai I Chik, Lai Pan Sze, Ming-Zhong Wang, Siu Wai Tsang and Hong-Jie Zhang*
Affiliation:
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR,China
Keywords:
Anti-cancer, anti-invasive, cancer stemness, EMT, CSC, STAT3, naphthoquinone, furanonaphthoquinone,
BBI608, natural products, chemical synthesis.
Abstract: Background: Cancer is a leading cause of mortality in the world and metastasis is to blame.
A number of naphthoquinones (NQs) have shown ability to reduce cancer stemness and metastatic potential.
Furano-naphthoquinones (FNQs), which is a class of NQ characterized by the incorporation of
an additional furan ring, have demonstrated improved anti-cancer potency as compared to the other
classes of NQs.
Objective: In this study, the natural origins, synthetic routes and derivatives of migrastatic NQs were
reviewed. The anti-invasive and anti-metastatic mechanisms of NQs and the more powerful FNQs in
targeting cancer were also discussed.
Methods: The articles related to the anti-invasive mechanisms of NQs were comprehensively reviewed.
The plant origins, synthetic routes and antitumor effects of more than 360 FNQs were also
covered and presented according to their chemical structures.
Results: Anti-cancer NQs inhibit cancer invasion by acting on epithelial-mesenchymal transition
(EMT), cancer stem cells (CSCs) and signal transducer and activator of transcription 3 (STAT3) signaling.
BBI608, a natural FNQ, has entered phases I and II clinical trials. It has been regarded as a potential
candidate for new-generation lead compound acting directly on CSCs to overcome the problem
of chemotherapy resistance. Apart from the plant-derived FNQs, there are a number of synthetic FNQs
that were found to intervene in cancer invasion and metastasis.
Conclusion: The anti-invasive mechanisms of NQs have been thoroughly studied. FNQs generally
show higher anti-cancer activity than that of NQs. The mechanisms of action of FNQs are worth further
investigation.
