PMID- 27769712
OWN - NLM
STAT- MEDLINE
DCOM- 20170131
LR  - 20211203
IS  - 1872-7786 (Electronic)
IS  - 0009-2797 (Linking)
VI  - 260
DP  - 2016 Dec 25
TI  - CWF-145, a novel synthetic quinolone derivative exerts potent antimitotic 
      activity against human prostate cancer: Rapamycin enhances antimitotic 
      drug-induced apoptosis through the inhibition of Akt/mTOR pathway.
PG  - 1-12
LID - S0009-2797(16)30470-7 [pii]
LID - 10.1016/j.cbi.2016.10.014 [doi]
AB  - CWF-145, a synthetic 2-phenyl-4-quinolone derivative exerted potent cytotoxicity 
      against prostate cancer. CWF-145 inhibited prostate cancer cell lines PC-3, 
      DU-145 and LNCap. It had a very low IC(50) about 200 nM against 
      castrate-resistant prostate cancer (CRPC) PC-3. We found that CWF-145 had a 
      similar effect to clinical trial antimitotic agents in cancer cells and normal 
      cells. CWF-145 arrested cell cycle at G2/M phase by binding to the beta-tubulin at 
      the colchicine-binding site then disrupted microtubule polymerization. 
      Furthermore, the damaged microtubule affected the Akt/mammalian target of 
      rapamycin (mTOR) signaling pathway. Our data showed that CWF-145 activated Akt 
      and mTOR expression to increase emi1 accumulation and inhibit APC. The increased 
      cyclin B1 and securin arrested cell cycle at G2/M phase. Moreover, we showed that 
      Akt activation markedly increased resistance to microtubule-directed agents, 
      including CWF-145, colchicine, and paclitaxel. Interestingly, rapamycin inhibited 
      Akt-mediated therapeutic resistance, indicating that these effects were dependent 
      on mTOR. Taken together, these observations suggest that activation of the 
      Akt/mTOR signaling pathway can promote resistance to chemotherapeutic agents that 
      do not directly target metabolic regulation. These data may provide insight into 
      potentially synergistic combinations of anticancer therapies.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Hung, Chao-Ming
AU  - Hung CM
AD  - Department of General Surgery, E-Da Hospital, I-Shou University, Kaohsiung, 
      Taiwan; School of Medicine, I-Shou University, Kaohsiung, Taiwan.
FAU - Lin, Ying-Chao
AU  - Lin YC
AD  - Division of Neurosurgery, Buddhist Tzu Chi General Hospital, Taichung Branch, 
      Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan; Department of 
      Medical Imaging and Radiological Science, Central Taiwan University of Science 
      and Technology, Taichung, Taiwan.
FAU - Liu, Liang-Chih
AU  - Liu LC
AD  - Department of Surgery, China Medical University Hospital, Taichung, Taiwan; 
      School of Medicine, College of Medicine, China Medical University, Taichung, 
      Taiwan.
FAU - Kuo, Sheng-Chu
AU  - Kuo SC
AD  - School of Pharmacy, College of Pharmacy, China Medical University, Taichung, 
      Taiwan.
FAU - Ho, Chi-Tang
AU  - Ho CT
AD  - Department of Food Science, Rutgers University, New Brunswick, NJ, USA.
FAU - Way, Tzong-Der
AU  - Way TD
AD  - Department of Biological Science and Technology, College of Biopharmaceutical and 
      Food Sciences, China Medical University, Taichung, Taiwan; Department of Health 
      and Nutrition Biotechnology, Asia University, Taichung, Taiwan. Electronic 
      address: tdway@mail.cmu.edu.tw.
LA  - eng
PT  - Journal Article
DEP - 20161018
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 (Antimitotic Agents)
RN  - 0 (CWF-145)
RN  - 0 (Quinolones)
RN  - 0 (Tubulin)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antimitotic Agents/chemistry/pharmacology/*therapeutic use
MH  - Apoptosis/*drug effects
MH  - Cell Cycle Checkpoints/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Humans
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Microtubules/drug effects/metabolism
MH  - Polymerization
MH  - Prostatic Neoplasms/*drug therapy/*pathology
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Quinolones/chemistry/pharmacology/*therapeutic use
MH  - Signal Transduction/drug effects
MH  - Sirolimus/*pharmacology
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tubulin/metabolism
MH  - Up-Regulation/drug effects
OTO - NOTNLM
OT  - Akt/mTOR
OT  - CWF-145
OT  - G2/M arrest
OT  - Prostate cancer
OT  - Rapamycin
EDAT- 2016/10/30 06:00
MHDA- 2017/02/01 06:00
CRDT- 2016/11/07 06:00
PHST- 2016/04/23 00:00 [received]
PHST- 2016/09/27 00:00 [revised]
PHST- 2016/10/17 00:00 [accepted]
PHST- 2016/10/30 06:00 [pubmed]
PHST- 2017/02/01 06:00 [medline]
PHST- 2016/11/07 06:00 [entrez]
AID - S0009-2797(16)30470-7 [pii]
AID - 10.1016/j.cbi.2016.10.014 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2016 Dec 25;260:1-12. doi: 10.1016/j.cbi.2016.10.014. Epub 
      2016 Oct 18.