Journal
JOURNAL OF ETHNOPHARMACOLOGY
Volume 202, Issue -, Pages 78-84Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.jep.2017.03.010
Keywords
AKR1B10; Amentoflavone; Anti-cancer; Combinatorial treatment; Doxorubicin; Selanginella tamariscina
Categories
Funding
- KIST intramural research grant [2Z04930, 2Z04610]
- Bio & Medical Technology Development Program of the National Research Foundation - Ministry of Science, ICT & Future Planning [NRF-2016M3A9D3915857]
- National Research Foundation of Korea [2016M3A9D3915857] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Ethnopharmacological relevance: Selaginella tamariscina (P.Beauv.) Spring is a traditional medicinal plant used to treat various human diseases, including cancer, in Asia. The detailed molecular mechanism underlying the anti-cancer effects of this plant and the anti-cancer action of the combinatorial treatment of S. tamariscina and doxorubicin have not yet been investigated. Aim of the study: We evaluated the inhibitory activity of S. tamariscina extract (STE) and its major compound, amentoflavone, on human aldo-keto reductase family 1B10 (AKR1B10), which is a detoxification enzyme involved in drug resistance, to evaluate their anti-cancer effects and their potential as adjuvant agents for doxorubicin cancer chemotherapy. Materials and methods: We tested the AKR1B10 inhibitory activity of STE and amentoflavone via an in vitro biochemical assay using recombinant human AKR1B10. We tested the anti-proliferative activity in A549, NCI-H460, SKOV-3, and MCF-7 human cancer cells, which contain different expression levels of AKR1B10, and determined the combination index to evaluate whether the addition of STE and amentoflavone is synergistic or antagonistic to the anti-cancer action of doxorubicin. We finally evaluated the in vivo anti-tumor effects of STE in a nude mouse xenograft model of A549 cells. Results: STE and amentoflavone potently inhibited human AKR1B10 and synergistically increased the doxorubicin anti-proliferative effect in A549 and NCI-H460 human lung cancer cells that express a high level of AKR1B10 mRNA and protein. STE also significantly inhibited A549 tumor growth in animal experiments. Conclusion: Our results suggest that STE and amentoflavone could be potential anti-cancer agents that target AKR1B10 and might be candidate adjuvant agents to boost the anti-cancer effect of doxorubicin.
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