PMID- 24960186
OWN - NLM
STAT- MEDLINE
DCOM- 20151102
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 6
DP  - 2014
TI  - Caffeic acid derivatives inhibit the growth of colon cancer: involvement of the 
      PI3-K/Akt and AMPK signaling pathways.
PG  - e99631
LID - 10.1371/journal.pone.0099631 [doi]
LID - e99631
AB  - BACKGROUND: The aberrant regulation of phosphatidylinositide 3-kinases 
      (PI3-K)/Akt, AMP-activated protein kinase (AMPK) and mammalian target of 
      rapamycin (m-TOR) signaling pathways in cancer has prompted significant interest 
      in the suppression of these pathways to treat cancer. Caffeic acid (CA) has been 
      reported to possess important anti-inflammatory actions. However, the molecular 
      mechanisms by which CA derivatives including caffeic acid phenethyl ester (CAPE) 
      and caffeic acid phenylpropyl ester (CAPPE), exert inhibitory effects on the 
      proliferation of human colorectal cancer (CRC) cells have yet to be elucidated. 
      METHODOLOGY/PRINCIPAL FINDINGS: CAPE and CAPPE were evaluated for their ability 
      to modulate these signaling pathways and suppress the proliferation of CRC cells 
      both in vitro and in vivo. Anti-cancer effects of these CA derivatives were 
      measured by using proliferation assays, cell cycle analysis, western blotting 
      assay, reporter gene assay and immunohistochemical (IHC) staining assays both in 
      vitro and in vivo. This study demonstrates that CAPE and CAPPE exhibit a 
      dose-dependent inhibition of proliferation and survival of CRC cells through the 
      induction of G0/G1 cell cycle arrest and augmentation of apoptotic pathways. 
      Consumption of CAPE and CAPPE significantly inhibited the growth of colorectal 
      tumors in a mouse xenograft model. The mechanisms of action included a modulation 
      of PI3-K/Akt, AMPK and m-TOR signaling cascades both in vitro and in vivo. In 
      conclusion, the results demonstrate novel anti-cancer mechanisms of CA 
      derivatives against the growth of human CRC cells. CONCLUSIONS: CA derivatives 
      are potent anti-cancer agents that augment AMPK activation and promote apoptosis 
      in human CRC cells. The structure of CA derivatives can be used for the rational 
      design of novel inhibitors that target human CRC cells.
FAU - Chiang, En-Pei Isabel
AU  - Chiang EP
AD  - Department of Food Science and Biotechnology, National Chung Hsing University, 
      Taichung, Taiwan, Republic of China; NCHU-UCD Plant and Food Biotechnology 
      Program and Agricultural Biotechnology Center, National Chung Hsing University, 
      Taichung, Taiwan, Republic of China.
FAU - Tsai, Shu-Yao
AU  - Tsai SY
AD  - Department of Health and Nutrition Biotechnology, Asia University, Taichung, 
      Taiwan, Republic of China.
FAU - Kuo, Yueh-Hsiung
AU  - Kuo YH
AD  - Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, 
      China Medical University, Taichung, Taiwan, Republic of China; Department of 
      Biotechnology, Asia University, Taichung, Taiwan, Republic of China.
FAU - Pai, Man-Hui
AU  - Pai MH
AD  - Department of Anatomy, Taipei Medical University, Taipei, Taiwan, Republic of 
      China.
FAU - Chiu, Hsi-Lin
AU  - Chiu HL
AD  - Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, 
      China Medical University, Taichung, Taiwan, Republic of China; Department of 
      Biotechnology, Asia University, Taichung, Taiwan, Republic of China.
FAU - Rodriguez, Raymond L
AU  - Rodriguez RL
AD  - Department of Molecular and Cellular Biology, University of California Davis, 
      Davis, California, United States of America.
FAU - Tang, Feng-Yao
AU  - Tang FY
AD  - Biomedical Science Laboratory, Department of Nutrition, China Medical University, 
      Taichung, Taiwan, Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140624
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (3-phenylpropyl caffeate)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Caffeic Acids)
RN  - G960R9S5SK (caffeic acid phenethyl ester)
RN  - ML9LGA7468 (Phenylethyl Alcohol)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Caffeic Acids/*pharmacology
MH  - Cell Cycle Checkpoints
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Colonic Neoplasms/*enzymology/pathology
MH  - HCT116 Cells
MH  - Humans
MH  - MAP Kinase Signaling System/*drug effects
MH  - Phenylethyl Alcohol/analogs & derivatives/pharmacology
PMC - PMC4069067
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/06/25 06:00
MHDA- 2015/11/03 06:00
PMCR- 2014/06/24
CRDT- 2014/06/25 06:00
PHST- 2013/07/03 00:00 [received]
PHST- 2014/05/16 00:00 [accepted]
PHST- 2014/06/25 06:00 [entrez]
PHST- 2014/06/25 06:00 [pubmed]
PHST- 2015/11/03 06:00 [medline]
PHST- 2014/06/24 00:00 [pmc-release]
AID - PONE-D-13-27431 [pii]
AID - 10.1371/journal.pone.0099631 [doi]
PST - epublish
SO  - PLoS One. 2014 Jun 24;9(6):e99631. doi: 10.1371/journal.pone.0099631. eCollection 
      2014.