PMID- 33050597
OWN - NLM
STAT- MEDLINE
DCOM- 20210517
LR  - 20210517
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 25
IP  - 20
DP  - 2020 Oct 11
TI  - Imipramine Inhibits Migration and Invasion in Metastatic Castration-Resistant 
      Prostate Cancer PC-3 Cells via AKT-Mediated NF-kappaB Signaling Pathway.
LID - 10.3390/molecules25204619 [doi]
LID - 4619
AB  - Imipramine (IMI) is a tricyclic synthetic antidepressant that is used to treat 
      chronic psychiatric disorders, including depression and neuropathic pain. IMI 
      also has inhibitory effects against various cancer types, including prostate 
      cancer; however, the mechanism of its anticancer activity is not well understood. 
      In the present study, we investigated the antimetastatic and anti-invasive 
      effects of IMI in metastatic castration-resistant prostate cancer PC-3 cells, 
      with an emphasis on the serine/threonine protein kinase AKT-mediated nuclear 
      factor kappa B (NF-kappaB) signaling pathway. While IMI did not induce cell death, it 
      attenuated PC-3 cell proliferation. According to the wound healing assay and 
      invasion assay, migration and invasion in PC-3 cells were significantly inhibited 
      by IMI in a dose-dependent manner. IMI significantly downregulated p-AKT protein 
      expression but upregulated phospho-extracellular signal-regulated kinase (ERK1)/2 
      protein expression levels. Furthermore, IMI treatment resulted in decreased 
      AKT-mediated downstream signaling, including p-inhibitor of kappaB kinase (IKK)alpha/beta, 
      p-inhibitor of kappaB (IkappaBalpha), and p-p65. Inhibited NF-kappaB signaling reduced the 
      secretion of several proinflammatory cytokines and chemokine by PC-3 cells. 
      Overall, our study explored the negative correlation between the use of 
      antidepressants and prostate cancer progression, showing that IMI attenuated cell 
      viability, migration, and invasion of PC-3 cells by suppressing the expression of 
      AKT and NF-kappaB-related signaling proteins and secretion of tumor necrosis factor-alpha 
      (TNF-alpha), interleukin-1beta (IL-1beta), and monocyte chemoattractant protein-1 (MCP-1).
FAU - Lim, Eun Yeong
AU  - Lim EY
AD  - Research group of Functional Food Materials, Korea Food Research Institute, 245, 
      Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea.
AD  - Department of Food Biotechnology, Korea University of Science & Technology, 217 
      Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea.
FAU - Park, Joon
AU  - Park J
AD  - Research group of Functional Food Materials, Korea Food Research Institute, 245, 
      Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea.
AD  - Department of Food Biotechnology, Korea University of Science & Technology, 217 
      Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea.
FAU - Kim, Yun Tai
AU  - Kim YT
AD  - Research group of Functional Food Materials, Korea Food Research Institute, 245, 
      Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, Korea.
AD  - Department of Food Biotechnology, Korea University of Science & Technology, 217 
      Gajeong-ro, Yuseong-gu, Daejeon 34113, Korea.
FAU - Kim, Min Jung
AU  - Kim MJ
AD  - Research group of Natural Materials and Metabolism, Korea Food Research 
      Institute, 245, Nongsaengmyeong-ro, Iseo-myeon, Wanju-gun, Jeollabuk-do 55365, 
      Korea.
LA  - eng
GR  - E0164500-05/Korea Food Research Institute/
PT  - Journal Article
DEP - 20201011
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (Antidepressive Agents)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - OGG85SX4E4 (Imipramine)
SB  - IM
MH  - Antidepressive Agents/pharmacology
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Imipramine/*pharmacology
MH  - Male
MH  - NF-kappa B/*metabolism
MH  - PC-3 Cells
MH  - Prostatic Neoplasms, Castration-Resistant/metabolism
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Wound Healing/drug effects
PMC - PMC7587212
OTO - NOTNLM
OT  - antidepressants
OT  - imipramine
OT  - invasion
OT  - migration
OT  - prostate cancer
COIS- The authors declare no conflicts of interest.
EDAT- 2020/10/15 06:00
MHDA- 2021/05/18 06:00
PMCR- 2020/10/11
CRDT- 2020/10/14 01:04
PHST- 2020/09/18 00:00 [received]
PHST- 2020/10/09 00:00 [revised]
PHST- 2020/10/10 00:00 [accepted]
PHST- 2020/10/14 01:04 [entrez]
PHST- 2020/10/15 06:00 [pubmed]
PHST- 2021/05/18 06:00 [medline]
PHST- 2020/10/11 00:00 [pmc-release]
AID - molecules25204619 [pii]
AID - molecules-25-04619 [pii]
AID - 10.3390/molecules25204619 [doi]
PST - epublish
SO  - Molecules. 2020 Oct 11;25(20):4619. doi: 10.3390/molecules25204619.