PMID- 30657763
OWN - NLM
STAT- In-Data-Review
LR  - 20190131
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 14
IP  - 1
DP  - 2019
TI  - Bromelain inhibits the ability of colorectal cancer cells to proliferate via
      activation of ROS production and autophagy.
PG  - e0210274
LID - 10.1371/journal.pone.0210274 [doi]
AB  - Advanced colorectal cancer (CRC) survival rates are still low despite advances in
      cytotoxic and targeted therapies. The development of new effective or alternative
      therapies is therefore urgently needed. Bromelain, an extract of pineapple, was
      shown to have anticancer effects, but its mechanisms in CRC have not been fully
      explored. Therefore, the roles of bromelain in CRC progression were investigated 
      using different CRC cell lines, a zebrafish model, and a xenograft mouse model.
      The anticancer mechanisms were explored by assessing the role of bromelain in
      inducing reactive oxygen species (ROS), superoxide, autophagosomes, and
      lysosomes. The role of bromelain in the induction of apoptosis was also assessed.
      It was found that bromelain inhibited CRC cell growth in cell lines and tumor
      growth in the zebrafish and xenograft mouse models. It also induced high levels
      of ROS and superoxide, plus autophagosome and lysosome formation. High levels of 
      apoptosis were also induced, which were associated with elevated amounts of
      apoptotic proteins like apoptotic induction factor, Endo G, and caspases-3, -8,
      and -9 according to a qPCR analysis. In a Western blot analysis, increases in
      levels of ATG5/12, beclin, p62, and LC3 conversion rates were found after
      bromelain treatment. Levels of cleaved caspase-3, caspase-8, caspase-9, and
      poly(ADP ribose) polymerase (PARP)-1 increased after bromelain exposure. This
      study explored the role of bromelain in CRC while giving insights into its
      mechanisms of action. This compound can offer a cheap alternative to current
      therapies.
FAU - Chang, Tung-Cheng
AU  - Chang TC
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical
      University, Taipei, Taiwan.
AD  - Department of Surgery, College of Medicine, Taipei Medical University, Taipei,
      Taiwan.
AD  - Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei
      Medical University, New Taipei City, Taiwan.
FAU - Wei, Po-Li
AU  - Wei PL
AUID- ORCID: http://orcid.org/0000-0002-7275-2661
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical
      University, Taipei, Taiwan.
AD  - Department of Surgery, College of Medicine, Taipei Medical University, Taipei,
      Taiwan.
AD  - Division of Colorectal Surgery, Department of Surgery, Taipei Medical University 
      Hospital, Taipei Medical University, Taipei, Taiwan.
AD  - Cancer Research Center and Translational Laboratory, Department of Medical
      Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, 
      Taiwan.
AD  - Graduate Institute of Cancer Biology and Drug Discovery, Taipei Medical
      University, Taipei, Taiwan.
FAU - Makondi, Precious Takondwa
AU  - Makondi PT
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical
      University, Taipei, Taiwan.
AD  - International PhD Program in Medicine, Taipei Medical University, Taipei, Taiwan.
FAU - Chen, Wei-Ting
AU  - Chen WT
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical
      University, Taipei, Taiwan.
FAU - Huang, Chien-Yu
AU  - Huang CY
AD  - Department of Surgery, College of Medicine, Taipei Medical University, Taipei,
      Taiwan.
AD  - Division of General Surgery, Department of Surgery, Shuang Ho Hospital, Taipei
      Medical University, New Taipei City, Taiwan.
FAU - Chang, Yu-Jia
AU  - Chang YJ
AUID- ORCID: http://orcid.org/0000-0003-3978-3244
AD  - Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical
      University, Taipei, Taiwan.
AD  - Cancer Research Center and Translational Laboratory, Department of Medical
      Research, Taipei Medical University Hospital, Taipei Medical University, Taipei, 
      Taiwan.
AD  - International PhD Program in Medicine, Taipei Medical University, Taipei, Taiwan.
LA  - eng
PT  - Journal Article
DEP - 20190118
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
PMC - PMC6338369
COIS- The authors have declared that no competing interests exist.
EDAT- 2019/01/19 06:00
MHDA- 2019/01/19 06:00
CRDT- 2019/01/19 06:00
PHST- 2018/07/15 00:00 [received]
PHST- 2018/12/19 00:00 [accepted]
PHST- 2019/01/19 06:00 [entrez]
PHST- 2019/01/19 06:00 [pubmed]
PHST- 2019/01/19 06:00 [medline]
AID - 10.1371/journal.pone.0210274 [doi]
AID - PONE-D-18-20941 [pii]
PST - epublish
SO  - PLoS One. 2019 Jan 18;14(1):e0210274. doi: 10.1371/journal.pone.0210274.
      eCollection 2019.