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.
Subject(s)
Antineoplastic Agents/therapeutic use , Furans/therapeutic use , Naphthoquinones/therapeutic use , Neoplasms/drug therapy , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Epithelial-Mesenchymal Transition/drug effects , Furans/chemical synthesis , Furans/pharmacology , Humans , Mice , Naphthoquinones/chemical synthesis , Naphthoquinones/pharmacology , Neoplastic Stem Cells/drug effectsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrata Matsum. & Koidz. is an endangered species of the Asteraceae family, growing in the high mountains of central Asia. It has been, and is, widely used in traditional Uyghur, Mongolian and Kazakhstan medicine as well as in Traditional Chinese Medicine as Tianshan Snow Lotus (Chinese: ). In traditional medical theory, S. involucrata can promote blood circulation, thereby alleviating all symptoms associated with poor circulation. It also reputedly eliminates cold and dampness from the body, diminishes inflammation, invigorates, and strengthens Yin and Yang. It has long been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in Uyghur and Chinese medicine. AIM OF THE REVIEW: To comprehensively summarize the miscellaneous research that has been done regarding the botany, ethnopharmacology, phytochemistry, biological activity, and toxicology of S. involucrata. METHOD: An extensive review of the literature was carried out. Apart from different electronic databases including SciFinder, Chinese National Knowledge Infrastructure (CNKI), ScienceDirect that were sourced for information, abstracts, full-text articles and books written in English and Chinese, including those traditional records tracing back to the Qing Dynasty. Pharmacopoeia of China and other local herbal records in Uighur, Mongolian and Kazakhstan ethnomedicines were investigated and compared for pertinent information. RESULTS: The phytochemistry of S. involucrata has been comprehensively investigated. More than 70 compounds have been isolated and identified; they include phenylpropanoids, flavonoids, coumarins, lignans, sesquiterpenes, steroids, ceramides, polysaccharides. Scientific studies on the biological activity of S. involucrata are equally numerous. The herb has been shown to have anti-neoplastic, anti-inflammatory, analgesic, anti-oxidative, anti-fatigue, anti-aging, anti-hypoxic, neuroprotective and immunomodulating effects. Many have shown correlations to the traditional clinical applications in Traditional Chinese Medicine and medicines. The possible mechanisms of S. involucrata in treating various cancers are revealed in the article, these include inhibition of cancer cells by affecting their growth, adhesion, migration, aggregation and invasion, inhibition of epidermal growth factor receptor signaling in cancer cells, hindrance of cancer cell proliferation, causing cytotoxicity to cancer cells and promoting expression of tumor suppressor genes. Dosage efficacy is found to be generally concentration- and time-dependent. However, studies on the correlation between particular chemical constituents and specific bioactivities are limited. CONCLUSION: In this review, we have documented the existing traditional uses of S. involucrata and summarized recent research into the phytochemistry and pharmacology of S. involucrata. Many of the traditional uses have been validated by phytochemical and modern pharmacological studies but there are still some areas where the current knowledge could be improved. Although studies have confirmed that S. involucrata has a broad range of bioactivities, further in-depth studies on the exact bioactive molecules and the mechanism of action are expected. Whether we should use this herb independently or in combination deserves to be clarified. The exact quality control as well as the toxicology studies is necessary to guarantee the stability and safety of the clinic use. The sustainable use of this endangered resource was also addressed. In conclusion, this review was anticipated to highlight the importance of S. involucrata and provides some directions for the future development of this plant.