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BMC Complement Altern Med. 2018 Jun 20;18(1):189. doi: 10.1186/s12906-018-2258-x.

Ethanol extracts from the branch of Taxillus yadoriki parasitic to Neolitsea sericea induces cyclin D1 proteasomal degradation through cyclin D1 nuclear export.

Author information

1
Department of Medicinal Plant Resources, Andong National University, Andong, 36729, Republic of Korea.
2
Forest Medicinal Resources Research Center, National Institute of Forest Science, Yongju, 36040, Republic of Korea.
3
Baekdudaegan National Arboretum, Bonghwa, 36209, Republic of Korea.
4
Department of Food Science & Biotechnology, Kyonggi University, Suwon, 16227, Republic of Korea.
5
Department of Medicinal Plant Resources, Andong National University, Andong, 36729, Republic of Korea. jjb0403@anu.ac.kr.
6
Agricultural Science and Technology Research Institute, Andong National University, Andong, 36729, Republic of Korea. jjb0403@anu.ac.kr.

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 Taxillus yadoriki (TY) parasitic to Neolitsea sericea (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 Cryptomeria japonica (CJ), Neolitsea sericea (NS), Prunus serrulata (PS), Cinnamomum camphora (CC) and Quercus acutissima (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 Taxillus yadoriki parasitic to Neolitsea sericea (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.

KEYWORDS:

Anticancer; Cell growth arrest; Cyclin D1; Mistletoe; Taxillus yadoriki

PMID:
29925351
PMCID:
PMC6011405
DOI:
10.1186/s12906-018-2258-x
[Indexed for MEDLINE]
Free PMC Article

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