A lignan from Alnus japonica inhibits glioblastoma tumorspheres by suppression of FOXM1

Introduction Glioblastoma (GBM) is the most common and aggressive malignant brain tumor. Forkhead Box M1 (FOXM1) has been shown to regulate cell proliferation, apoptosis, angiogenesis, DNA damage repair and tumorigenesis. The lignin, (−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol (DFS), from Alnus japonica (Betulaceae) has shown anti-cancer effects against colon cancer cells by suppressing FOXM1. However, the efficacy of DFS in GBM has not yet been determined. The present study hypothesized that DFS can have anti-cancer effects against GBM tumorspheres (TSs). Methods Immunoprecipitation and luciferase reporter assays were performed to evaluate the ability of DFS to suppress nuclear translocation of β-catenin through β-catenin/FOXM1 binding. GBM TSs were treated with DFS to assess the ability of DFS to inhibit GBM TSs and to evaluate their transcriptional profiles. The in vivo efficacy of DFS was examined in orthotopic xenograft models of GBM. Results Expression of FOXM1 was higher in GBM than in normal tissues. DFS-induced FOXM1 protein degradation blocked β-catenin translocation into the nucleus and consequently suppressed downstream target genes of FOXM1 pathways. DFS considerably inhibited cell viability and ATP levels in GBM TSs, while increasing the proportion of apoptotic cells. Treatment with DFS also reduced neurosphere formation and the invasive properties of GBM TSs. Transcriptome analyses showed that DFS reduced the activities of transcription factors related to tumorigenesis, stemness, and invasiveness. In addition, DFS significantly inhibited tumor growth and prolonged the survival rate of mice in orthotopic xenograft models of GBM. Conclusions DFS inhibits the proliferation of GBM TSs by suppressing FOXM1. These findings suggest that DFS may be a potential therapeutic agent to treat patients with GBM.

Forests of Japanese alder in the Russian Far East: the new association of the class Alnetea japonicae Miyawaki et al. 1977

We describe the new association Lycopo lucidi–Alnetum japonicae Korznikov, Verkholat & Krestov 2021 ass. nov. of the Alnus japonica swampy forests of the coastal plains and river valleys in the south of the Primorye Territory of Russia. The association includes two subassociations: Lycopo lucidi–Alnetum japonicae typicum Korznikov, Verkholat & Krestov 2021 subass. nov. and the preliminary delineated Lycopo lucidi–Alnetum japonicae betuletosum davuricae subass. prov. developing on gently sloping foothills with a lateral inflow of moisture and is transitional to zonal broad-leaved forests of the class Quercetea mongolicae Song ex Krestov et al. 2006. The association is classified to the alliance Fraxino–Alnion japonicae Miyawaki et al. 1977 described from Japan and belonging to the order Alnetalia japonicae Miyawaki et al. 1977 and the class Alnetea japonicae Miyawaki et al. 1977. We also validate the name of the association Stellario longifoliae–Alnetum japonicae Ohno in Miyawaki 1988 nom. inval. (art. 5) from Hokkaido Island, Northern Japan.

Lignan from Alnus japonica Inhibits Adipocyte Differentiation via Cell Cycle and FOXO1 Regulation

In the present study, we isolated a lignan ((−)-(2R,3R)-1,4-O-diferuloylsecoisolariciresinol, DFS) from Alnus japonica and evaluated its antiobesity potential in vitro. We also determined its mechanism of action in a mouse pre-adipocyte 3T3-L1 cell line. DFS dose- and day-dependently inhibited adipogenesis by downregulation of adipogenic factors and lipid metabolism-regulating factors during adipocyte differentiation. In particular, DFS suppressed cell cycle-regulating factors and induced G0/G1 cell cycle arrest, implying that it had an inhibitory effect on mitotic clonal expansion which occurred at an early stage of adipogenesis. DFS also suppressed adipogenesis through decreasing Akt phosphorylation and increasing the level of Forkhead box protein-O1 (FOXO1). These results suggest that DFS may be a pharmacological candidate for the development of antiobesity, therapeutic, and nutraceutical products.