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Anticancer activity of calyx of Diospyros kaki Thunb. through downregulation of cyclin D1 via inducing proteasomal degradation and transcriptional inhibition in human colorectal cancer cells.

Abstract Although it has been reported to contain high polyphenols, the pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been elucidated in detail. In this study, we elucidated anti-cancer activity and potential molecular mechanism of DKC against human colorectal cancer cells.
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Authors

Mayor MeshTerms
Keywords

Anticancer

Calyx of persimmon

Cyclin D1

Diospyros kaki Thunb.

Human colorectal cancer

Journal Title bmc complementary and alternative medicine
Publication Year Start




PMID- 28870200
OWN - NLM
STAT- MEDLINE
DA  - 20170905
DCOM- 20170908
LR  - 20170908
IS  - 1472-6882 (Electronic)
IS  - 1472-6882 (Linking)
VI  - 17
IP  - 1
DP  - 2017 Sep 05
TI  - Anticancer activity of calyx of Diospyros kaki Thunb. through downregulation of
      cyclin D1 via inducing proteasomal degradation and transcriptional inhibition in 
      human colorectal cancer cells.
PG  - 445
LID - 10.1186/s12906-017-1954-2 [doi]
AB  - BACKGROUND: Although it has been reported to contain high polyphenols, the
      pharmacological studies of the calyx of Diospyros kaki Thunb (DKC) have not been 
      elucidated in detail. In this study, we elucidated anti-cancer activity and
      potential molecular mechanism of DKC against human colorectal cancer cells.
      METHODS: Anti-cell proliferative effect of 70% ethanol extracts from the calyx of
      Diospyros kaki (DKC-E70) was evaluated by MTT assay. The effect of DKC-E70 on the
      expression of cyclin D1 in the protein and mRNA level was evaluated by Western
      blot and RT-PCR, respectively. RESULTS: DKC-E70 suppressed the proliferation of
      human colorectal cancer cell lines such as HCT116, SW480, LoVo and HT-29.
      Although DKC-E70 decreased cyclin D1 expression in protein and mRNA level,
      decreased level of cyclin D1 protein by DKC-E70 occurred at the earlier time than
      that of cyclin D1 mRNA, which indicates that DKC-E70-mediated downregulation of
      cyclin D1 protein may be a consequence of the induction of degradation and
      transcriptional inhibition of cyclin D1. In cyclin D1 degradation, we found that 
      cyclin D1 downregulation by DKC-E70 was attenuated in presence of MG132. In
      addition, DKC-E70 phosphorylated threonine-286 (T286) of cyclin D1 and T286A
      abolished cyclin D1 downregulation by DKC-E70. We also observed that
      DKC-E70-mediated T286 phosphorylation and subsequent cyclin D1 degradation was
      blocked in presence of the inhibitors of ERK1/2, p38 or GSK3beta. In cyclin D1
      transcriptional inhibition, DKC-E70 inhibited the expression of beta-catenin and 
      TCF4, and beta-catenin/TCF-dependent luciferase activity. CONCLUSIONS: Our
      results suggest that DKC-E70 may downregulate cyclin D1 as one of the potential
      anti-cancer targets through cyclin D1 degradation by T286 phosphorylation
      dependent on ERK1/2, p38 or GSK3beta, and cyclin D1 transcriptional inhibition
      through Wnt signaling. From these findings, DKC-E70 has potential to be a
      candidate for the development of chemoprevention or therapeutic agents for human 
      colorectal cancer.
FAU - Park, Su Bin
AU  - Park SB
AD  - Department of Medicinal Plant Resources, Andong National University, Andong,
      36729, Republic of Korea.
FAU - Park, Gwang Hun
AU  - Park GH
AD  - Department of Medicinal Plant Resources, Andong National University, Andong,
      36729, Republic of Korea.
AD  - Forest Medicinal Resources Research Center, National Institute of Forest Science,
      Yeongju, 36040, Republic of Korea.
FAU - Song, Hun Min
AU  - Song HM
AD  - Department of Medicinal Plant Resources, Andong National University, Andong,
      36729, Republic of Korea.
FAU - Son, Ho-Jun
AU  - Son HJ
AD  - Forest Medicinal Resources Research Center, National Institute of Forest Science,
      Yeongju, 36040, Republic of Korea.
FAU - Um, Yurry
AU  - Um Y
AD  - Forest Medicinal Resources Research Center, National Institute of Forest Science,
      Yeongju, 36040, Republic of Korea.
FAU - Kim, Hyun-Seok
AU  - Kim HS
AD  - Department of Food Science & Biotechnology, Kyonggi University, Suwon, 16227,
      Republic of Korea.
FAU - Jeong, Jin Boo
AU  - Jeong JB
AD  - Department of Medicinal Plant Resources, Andong National University, Andong,
      36729, Republic of Korea. [email protected]
AD  - Insititute of Agricultural Science and Technology, Andong National University,
      Andong, 36729, Republic of Korea. [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170905
PL  - England
TA  - BMC Complement Altern Med
JT  - BMC complementary and alternative medicine
JID - 101088661
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Plant Extracts)
RN  - 0 (beta Catenin)
RN  - 136601-57-5 (Cyclin D1)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Antineoplastic Agents/*administration & dosage
MH  - Cell Proliferation/drug effects
MH  - Colorectal Neoplasms/drug therapy/*genetics/metabolism/physiopathology
MH  - Cyclin D1/*genetics/*metabolism
MH  - Diospyros/*chemistry
MH  - HCT116 Cells
MH  - HT29 Cells
MH  - Humans
MH  - Phosphorylation
MH  - Plant Extracts/*administration & dosage
MH  - Proteasome Endopeptidase Complex/genetics/*metabolism
MH  - Proteolysis
MH  - beta Catenin/genetics/metabolism
PMC - PMC5584323
OTO - NOTNLM
OT  - Anticancer
OT  - Calyx of persimmon
OT  - Cyclin D1
OT  - Diospyros kaki Thunb.
OT  - Human colorectal cancer
EDAT- 2017/09/06 06:00
MHDA- 2017/09/09 06:00
CRDT- 2017/09/06 06:00
PHST- 2017/03/09 [received]
PHST- 2017/08/30 [accepted]
AID - 10.1186/s12906-017-1954-2 [doi]
AID - 10.1186/s12906-017-1954-2 [pii]
PST - epublish
SO  - BMC Complement Altern Med. 2017 Sep 5;17(1):445. doi: 10.1186/s12906-017-1954-2.