title: AKR1B10-inhibitory Selaginella tamariscina extract and amentoflavone decrease the growth of A549 human lung cancer cells in vitro and in vivo.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Jung
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea.
authors.forename: Eun Ha
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Republic of Korea.
authors.forename: Chang Gun
authors.initials: CG
authors.lastname: Lee
authors.affiliation: Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University, Wonju 26493, Republic of Korea.
authors.forename: Ki-Jong
authors.initials: KJ
authors.lastname: Rhee
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea.
authors.forename: Woo-Suk
authors.initials: WS
authors.lastname: Jung
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea; Department of Biological Chemistry, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.
authors.forename: Yongsoo
authors.initials: Y
authors.lastname: Choi
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea; Department of Biological Chemistry, University of Science and Technology (UST), Daejeon 34113, Republic of Korea. Electronic address: panc@kist.re.kr.
authors.forename: Cheol-Ho
authors.initials: CH
authors.lastname: Pan
authors.affiliation: Systems Biotechnology Research Center, Korea Institute of Science and Technology, Gangneung 25451, Republic of Korea; Department of Biological Chemistry, University of Science and Technology (UST), Daejeon 34113, Republic of Korea. Electronic address: kskang@kist.re.kr.
authors.forename: Kyungsu
authors.initials: K
authors.lastname: Kang
mesh_terms: D000072283:A549 Cells; D000277:Adjuvants, Pharmaceutic; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000074408:Aldo-Keto Reductases; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D044946:Biflavonoids / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D051379:Mice; D010936:Plant Extracts / Q000494:pharmacology*; D032503:Selaginellaceae / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000277:Adjuvants, Pharmaceutic; D000903:Antibiotics, Antineoplastic; D044946:Biflavonoids; D010936:Plant Extracts; D004317:Doxorubicin; C011164:amentoflavone; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase
keywords: AKR1B10; Amentoflavone; Amentoflavone (PubChem CID: 5281600); Anti-cancer; Combinatorial treatment; Doxorubicin; Doxorubicin hydrochloride (PubChem CID: 443939); Epalrestat (PubChem CID: 1549120); Selanginella tamariscina