Proanthocyanidins inhibited colorectal cancer stem cell characteristics through Wnt/ß-catenin signaling.
Environ Toxicol
; 38(12): 2894-2903, 2023 Dec.
Article
in En
| MEDLINE
| ID: mdl-37551626
ABSTRACT
BACKGROUND:
Cancer stem cells (CSCs) play a key role in tumor cell growth, drug resistance, recurrence, and metastasis. Proanthocyanidins (PC) is widely existed in plants and endowed with powerful antioxidant and anti-aging effects. Interestingly, recent studies have found that PC exhibits the inhibitory effect on tumor growth. However, the role of PC in CSCs of colorectal cancer (CRC) and molecular mechanism remain unclear.METHODS:
CCK-8, colony, and tumorsphere formation assay were used to evaluate cancer cell viability and stemness, respectively. Western blotting was used to detect the protein expression. Tumor xenograft experiments were employed to examine the tumorigenicity of CRC cells in nude mice.RESULTS:
PC decreased the proliferation of CRC cells (HT29 and HCT-116), and improved the sensitivity of CRC cells to oxaliplatin (L-OHP), as well as inhibited tumor growth in nude mice. Further studies showed that PC also down-regulated CSCs surface molecular and stemness transcriptional factors, while suppressed the formations of tumorspheres and cell colony in CRC. In addition, PC-impaired proteins expressions of p-GSK3ß, ß-catenin and DVL1-3. LiCl, an activator of the Wnt/ß-catenin signaling, rescued PC-induced downregulation of CSCs markers, and reduction of tumorspheres and cell colony formation abilities in CRC cells. Furthermore, the effects of PC on inhibiting cell proliferation and enhancing L-OHP sensitivity were impaired by LiCl.CONCLUSIONS:
PC exerted an inhibitory effect on CSCs via Wnt/ß-catenin in CRC, and may be a potential new class of natural drug for CRC treatment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Proanthocyanidins
Limits:
Animals
/
Humans
Language:
En
Journal:
Environ Toxicol
Journal subject:
SAUDE AMBIENTAL
/
TOXICOLOGIA
Year:
2023
Type:
Article
Affiliation country:
China