Cinnamaldehyde inhibits pancreatic cancer cell proliferation and sternness via modulation of CD44s/STAT3 signaling pathway
- Author:
Su-Li ZHU
1
;
Xing-Wang ZHOU
1
;
Yun-Hao CHEN
2
;
Jian-Ping YAO
3
Author Information
- Publication Type:Journal Article
- Keywords: cancer cell stemness; CD44s/STAT3 signaling pathway; cinnamaldehyde; PANC-1 cells; pancreatic cancer; proliferation
- From: Chinese Pharmacological Bulletin 2022;38(5):676-683
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the effects of cinnamaldehyde on the proliferation and stemness of pancreatic cancer PANC-1 cells, and its possible mechanism of action.Methods CCK8 assay was used to detect the effect of cinnamaldehyde treatment on cell viability at different concentrations(0, 5, 15, 20, 30, 50, 70, 100, 150 μmol·L-1)and different intervention time(24, 48, 72 h).CFSE proliferation assay was used to detect the inhibitory effects of cinnamaldehyde on PANC-1 cells.Colony formation assay was employed to determine the colony-forming ability of PANC-1 cells after cinnamaldehyde treatment.The sphere formation assay was employed to detect the effects of cinnamaldehyde on sphere-forming ability in PANC-1 cells.Western blot analysis and qRT-PCR analysis were applied to determine the expression levels of Nanog, Sox-2 and Oct-4.Flow cytometry was used to detect the percentage of CD44+CD24+ cells and ALDH+ cells in cinnamaldehyde treated and untreated PANC-1 cells.Western blot analysis was used to detect the effects of cinnamaldehyde on the expression of CD44s, p-STAT3 and STAT3 in PANC-1 cells.Results Cinnamaldehyde suppressed cell viability in a dose- and time-dependent manner, and inhibited tumor-cell proliferation and colony forming ability significantly in a dose-dependent manner in PANC-1 cells.Sphere-forming assay showed that cinnamaldehyde could significantly inhibit sphere-forming ability in suspension culture of PANC-1 cells.The mRNA and protein expression levels of three stemness-related genes were down-regulated after cinnamaldehyde treatment.In addition, cinnamaldehyde treatment significantly decreased the proportion of CD44+CD24+ cells and ALDH+ cells.Western blotting showed that cinnamaldehyde inhibited the expression of CD44s and p-STAT3, while it had no effect on the expression of STAT3.With the addition of STAT3 activator(Colivelin TFA), the inhibition of cinnamaldehyde on proliferation and tumor-cell stemness in PANC-1 cells was partially rescued.Conclusions Cinnamaldehyde significantly inhibits the proliferation and tumor-cell stemness of pancreatic cancer PANC-1 cells, and the mechanism could be related to the modulation of CD44s/STAT3 signaling pathway.
