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- Title
Ethanol extracts from the branch of <italic>Taxillus yadoriki</italic> parasitic to <italic>Neolitsea sericea</italic> induces cyclin D1 proteasomal degradation through cyclin D1 nuclear export.
- Authors
Park, Su Bin; Park, Gwang Hun; Kim, Ha Na; Song, Hun Min; Son, Ho-Jun; Park, Ji Ae; Kim, Hyun-Seok; Jeong, Jin Boo
- Abstract
Background: Although the inhibitory effect of mistletoe on cancer cell growth has been reported, the underlying mechanisms to explain its anti-proliferative activity are not fully studied. Thus, we elucidated the potential molecular mechanism of the branch from <italic>Taxillus yadoriki</italic> (TY) parasitic to <italic>Neolitsea sericea</italic> (NS) (TY-NS-B) for the anti-proliferative effect. Methods: Anti-cell proliferative effect was evaluated by MTT assay. The change of cyclin D1 protein or mRNA level was evaluated by Western blot and RT-RCR, respectively. Results: In comparison of anti-proliferative effect of TY from the host trees such as <italic>Cryptomeria japonica</italic> (CJ), <italic>Neolitsea sericea</italic> (NS), <italic>Prunus serrulata</italic> (PS), <italic>Cinnamomum camphora</italic> (CC) <italic>and Quercus acutissima</italic> (QA), TY-NS showed higher anti-cell proliferative effect than TY-CJ, TY-PS, TY-CC or TY-QA. In addition, the anti-proliferative effect of branch from TY from all host trees was better than leaves. Thus, we selected the branch from <italic>Taxillus yadoriki</italic> parasitic to <italic>Neolitsea sericea</italic> (TY-NS-B) for the further study. TY-NS-B inhibited the cell proliferation in the various cancer cells and downregulated cyclin D1 protein level. MG132 treatment attenuated cyclin D1 downregulation of cyclin D1 protein level by TY-NS-B. In addition, TY-NS-B increased threonine-286 (T286) phosphorylation of cyclin D1, and the mutation of T286 to alanine (T286A) blocked cyclin D1 proteasomal degradation by TY-NS-B. But the upstream factors related to cyclin D1 degradation such as ERK1/2, p38, JNK, GSK3β, PI3K, IκK or ROS did not affect cyclin D1 degradation by TY-NS-B. However, LMB treatment was observed to inhibit cyclin D1 degradation by TY-NS-B, and T286A blocked cyclin D1 degradation through suppressing cyclin D1 redistribution from nucleus to cytoplasm by TY-NS-B. In addition, TY-NS-B activated CRM1 expression. Conclusions: Our results suggest that TY-NS-B may suppress cell proliferation by downregulating cyclin D1 protein level through proteasomal degradation via T286 phosphorylation-dependent cyclin D1 nuclear export. These findings will provide the evidence that TY-NS-B has potential to be a candidate for the development of chemoprevention or therapeutic agents for human cancer.
- Subjects
VISCUM; TUMORS; PLANT extracts; TREATMENT effectiveness; PROSTAGLANDINS I; THERAPEUTICS
- Publication
BMC Complementary & Alternative Medicine, 2018, Vol 18, Issue 1, p1
- ISSN
1472-6882
- Publication type
Article
- DOI
10.1186/s12906-018-2258-x