Luteolin decreases invasiveness, deactivates STAT3 signaling, and reverses interleukin-6 induced epithelial–mesenchymal transition and matrix metalloproteinase secretion of pancreatic cancer cells

Abstract

Luteolin, a flavone, has been shown to exhibit anticancer properties. Here, we investigated whether luteolin affects epithelial–mesenchymal transition (EMT) and invasiveness of pancreatic cancer cell lines and their underlying mechanism. Pancreatic cancer cell lines PANC-1 and SW1990 were used in our study, and their EMT characters, matrix metalloproteinase (MMP) expression level, invasiveness, and signal transducer and activator of transcription 3 (STAT3) activity were determined after luteolin treatment. We also treated pancreatic cancer cells with interleukin-6 (IL-6) to see whether IL-6-induced activation of STAT3, EMT, and MMP secretion was affected by luteolin. We found that luteolin inhibits EMT and MMP2, MMP7, and MMP9 expression in a dose-dependent manner, similar to STAT3 signaling. Through Transwell assay, we found that invasiveness of pancreatic cancer cells was inhibited by luteolin. EMT characters and MMP secretion increase with STAT3 activity after IL-6 treatment and these effects, caused by IL-6, were inhibited by luteolin. We concluded that luteolin inhibits invasiveness of pancreatic cancer cells, and we speculated that luteolin inhibits EMT and MMP secretion likely through deactivation of STAT3 signaling. Luteolin has potential antitumor effects and merits further investigation.

Dermokine contributes to epithelial–mesenchymal transition through increased activation of signal transducer and activator of transcription 3 in pancreatic cancer

“…Signal transducer and activator of transcription 3 is activated by numerous cytokine receptor‐associated tyrosine kinases, growth factor receptors with intrinsic tyrosine kinase activity, and oncogenic proteins; making STAT3 signaling central to the regulation of cancer invasion and metastasis. Moreover, our previous study showed that several genes downstream of the activated STAT3 pathway were closely related to EMT . In the present study, DMKN‐shRNA‐transfected PDAC cells showed lower expression of N‐cadherin, vimentin, and Snail, but higher expression of E‐cadherin.…”

“…Moreover, our previous study showed that several genes downstream of the activated STAT3 pathway were closely related to EMT. (31) In the present study, DMKN-shRNA-transfected PDAC cells showed lower expression of N-cadherin, vimentin, and Snail, but higher expression of E-cadherin. At the same time, STAT3 activity also modulated the level of DMKN.…”

Isoorientin induces apoptosis, decreases invasiveness, and downregulates VEGF secretion by activating AMPK signaling in pancreatic cancer cells

“…Bioassay-directed fractionation techniques led to the isolation of isoorientin as the main hypoglycemic component in Gentiana olivieri 8. Our team confirmed that luteolin has a strong anticancer effect in PC 9. The effects of isoorientin, as a 6-C-glucoside of luteolin, on cancer need to be identified.…”

Luteolin Promotes Cell Apoptosis by Inducing Autophagy in Hepatocellular Carcinoma

“…Plants rich in luteolin have been used in Chinese traditional medicine to treat various diseases, such as hypertension, inflammatory disorders, and cancer [3, 4]. The anti-cancer activities of luteolin have been demonstrated in many cancer cells, such as pancreatic cancer, prostate cancer, breast cancer, colorectal cancer, and ovarian cancer [5-8]. In addition, luteolin could upregulate the mRNA expression level of intercellular adhesion molecule-1, a tumor suppressor gene [9], in mouse H22 hepatoma cells [10].…”