PMID- 29262645
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 61
DP  - 2017 Nov 28
TI  - Therapeutic effects of the euglenoid ichthyotoxin, euglenophycin, in colon 
      cancer.
PG  - 104347-104358
LID - 10.18632/oncotarget.22238 [doi]
AB  - Colorectal cancer (CRC) remains one of the most commonly diagnosed cancers and 
      the 3(rd) leading cause of cancer-related mortality. The emergence of drug 
      resistance poses a major challenge in CRC care or treatment. This can be 
      addressed by determining cancer mechanisms, discovery of druggable targets, and 
      development of new drugs. In search for novel agents, aquatic microorganisms 
      offer a vastly untapped pharmacological source that can be developed for cancer 
      therapeutics. In this study, we characterized the anti-colorectal cancer 
      potential of euglenophycin, a microalgal toxin from Euglena sanguinea. The toxin 
      (49.1-114.6 muM) demonstrated cytotoxic, anti-proliferative, anti-clonogenic, and 
      anti-migration effects against HCT116, HT29, and SW620 CRC cells. We identified 
      G1 cell cycle arrest and cell type - dependent modulation of autophagy as 
      mechanisms of growth inhibition. We validated euglenophycin's anti-tumorigenic 
      activity in vivo using CRL:Nu(NCr)Foxn1(nu) athymic nude mouse CRC xenograft 
      models. Intraperitoneal toxin administration (100 mg/kg; 5 days) decreased HCT116 
      and HT29 xenograft tumor volumes (n=10 each). Tumor inhibition was associated 
      with reduced expression of autophagy negative regulator mechanistic target of 
      rapamycin (mTOR) and decreased trend of serum pro-inflammatory cytokines. 
      Together, these results provide compelling evidence that euglenophycin can be a 
      promising anti-colorectal cancer agent targeting multiple cancer-promoting 
      processes. Furthermore, this study supports expanding natural products drug 
      discovery to freshwater niches as prospective sources of anti-cancer compounds.
FAU - Cabang, April B
AU  - Cabang AB
AD  - Department of Molecular Medicine, University of Texas Health Science Center at 
      San Antonio, San Antonio, TX 78229, USA.
FAU - De Mukhopadhyay, Keya
AU  - De Mukhopadhyay K
AD  - Department of Molecular Medicine, University of Texas Health Science Center at 
      San Antonio, San Antonio, TX 78229, USA.
FAU - Meyers, Sarah
AU  - Meyers S
AD  - College of Charleston, Charleston, SC 29424, USA.
FAU - Morris, Jay
AU  - Morris J
AD  - Department of Molecular Medicine, University of Texas Health Science Center at 
      San Antonio, San Antonio, TX 78229, USA.
FAU - Zimba, Paul V
AU  - Zimba PV
AD  - Center for Coastal Studies and Department of Life Sciences, Texas A&M - Corpus 
      Christi, Corpus Christi, TX 78412, USA.
FAU - Wargovich, Michael J
AU  - Wargovich MJ
AD  - Department of Molecular Medicine, University of Texas Health Science Center at 
      San Antonio, San Antonio, TX 78229, USA.
LA  - eng
PT  - Journal Article
DEP - 20171101
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5732811
OTO - NOTNLM
OT  - autophagy
OT  - colon cancer
OT  - euglenophycin
OT  - ichthyotoxin
OT  - therapy
COIS- CONFLICTS OF INTEREST The authors have no potential conflicts of interest.
EDAT- 2017/12/22 06:00
MHDA- 2017/12/22 06:01
PMCR- 2017/11/28
CRDT- 2017/12/22 06:00
PHST- 2017/08/16 00:00 [received]
PHST- 2017/10/13 00:00 [accepted]
PHST- 2017/12/22 06:00 [entrez]
PHST- 2017/12/22 06:00 [pubmed]
PHST- 2017/12/22 06:01 [medline]
PHST- 2017/11/28 00:00 [pmc-release]
AID - 22238 [pii]
AID - 10.18632/oncotarget.22238 [doi]
PST - epublish
SO  - Oncotarget. 2017 Nov 1;8(61):104347-104358. doi: 10.18632/oncotarget.22238. 
      eCollection 2017 Nov 28.