Saffron Crudes and Compounds Restrict MACC1-Dependent Cell Proliferation and Migration of Colorectal Cancer Cells.
Antineoplastic Agents
/ chemistry
Carotenoids
/ analysis
Cell Cycle Checkpoints
/ drug effects
Cell Line, Tumor
Cell Movement
/ drug effects
Cell Proliferation
/ drug effects
Cell Survival
/ drug effects
Colorectal Neoplasms
/ genetics
Crocus
/ chemistry
Doublecortin-Like Kinases
Gene Expression Regulation, Neoplastic
/ drug effects
Humans
Intracellular Signaling Peptides and Proteins
/ genetics
Plant Extracts
/ chemistry
Protein Serine-Threonine Kinases
/ genetics
Trans-Activators
/ genetics
DCLK1
MACC1
colorectal cancer
metastasis
natural compounds
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
03 08 2020
03 08 2020
Historique:
received:
29
06
2020
revised:
29
07
2020
accepted:
01
08
2020
entrez:
7
8
2020
pubmed:
7
8
2020
medline:
11
3
2021
Statut:
epublish
Résumé
The high mortality rate of colorectal cancer (CRC) patients is directly associated with metastatic dissemination. However, therapeutic options specifically for metastasis are still limited. We previously identified Metastasis-Associated in Colon Cancer 1 (MACC1) as a major causal metastasis-inducing gene. Numerous studies confirmed its value as a biomarker for metastasis risk. We investigated the inhibitory impact of saffron on MACC1-induced cancer cell growth and motility. Saffron crudes restricted the proliferation and migration of MACC1-expressing CRC cells in a concentration- and MACC1-dependent manner. Saffron delays cell cycle progression at G2/M-phase and does not induce apoptosis. Rescue experiments showed that these effects are reversible. Analysis of active saffron compounds elucidated that crocin was the main compound that reproduced total saffron crudes effects. We showed the interaction of MACC1 with the cancer stem cell (CSC) marker DCLK1, which contributes to metastasis formation in different tumor entities. Saffron extracts reduced DCLK1 with crocin being responsible for this reduction. Saffron's anti-proliferative and anti-migratory effects in MACC1-expressing cells are mediated by crocin through DCLK1 down-regulation. This research is the first identification of saffron-based compounds restricting cancer cell proliferation and motility progression via the novel target MACC1.
Identifiants
pubmed: 32756469
pii: cells9081829
doi: 10.3390/cells9081829
pmc: PMC7463853
pii:
doi:
Substances chimiques
Antineoplastic Agents
0
Intracellular Signaling Peptides and Proteins
0
MACC1 protein, human
0
Plant Extracts
0
Trans-Activators
0
Carotenoids
36-88-4
crocin
877GWI46C2
DCLK1 protein, human
EC 2.7.1.11
Doublecortin-Like Kinases
EC 2.7.1.11
Protein Serine-Threonine Kinases
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
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