Umbelliprenin induces autophagy and apoptosis while inhibits cancer cell stemness in pancreatic cancer cells

Abstract

BackgroundUmbelliprenin is a sesquiterpene coumarin isolated from Artemisia absinthium L. and shows antitumor effects in various cancers by inducing apoptosis. However, the antitumor effect of umbelliprenin in human pancreatic cancer has not been clarified.MethodsThe antitumor effects were determined by MTT and AnnexinV/PI double staining assay in vitro and xenograft mice in vivo. Autophagy was determined via immunofluorescence analysis. Apoptotic or autophagic related proteins were measured by immunoblotting. The pancreatic cancer cell stemness were determined by mammosphere formation and ALDEFLUOR assay.ResultsIt revealed that umbelliprenin inhibited pancreatic cancer cell proliferation in vitro and pancreatic cancer tumor growth in vivo. Moreover, umbelliprenin induced pancreatic cancer cell BxPC3 apoptosis and autophagy as evidenced by upregulated apoptosis and autophagy‐ related protein expression (p < 0.01). Blocking autophagy by 3‐MA or Atg7 knockout enhanced umbelliprenin‐induced apoptosis (p < 0.05). Umbelliprenin also reduced pancreatic cancer cell stemness by reducing Oct4, Nanog, and Sox2 mRNA levels (p < 0.01). Mechanistically, umbelliprenin greatly inhibited Akt/mTOR and Notch1 signal pathway.ConclusionUmbelliprenin may be a novel therapeutic approach for pancreatic cancer treatment.

Degradable Polymer-Based Nanoassemblies for Precise Targeting and Drug Delivery to Breast Cancer Cells without Affecting Normal Healthy Cells

“…In a typical experiment, MDAMB-231 cells treated with 4 μg/mL DOX and PU-SS@DOX, wound healing was inhibited by approximately 18 and 23%, respectively, whereas the control wound recovered about 75% in 48 h, indicating the efficacy of PU-SS@DOX in impairing cellular migration. Further, the in vitro sphere inhibition assay was carried out, as TNBC has a high number of breast cancer stem-like cells (BCSCs), which contribute considerably to the disease’s poor prognosis, metastasis, and relapse . Thus, targeting BCSCs may be a promising strategy for combating TNBC.…”

Sesquiterpenes and Sesquiterpene Derivatives from Ferula: Their Chemical Structures, Biosynthetic Pathways, and Biological Properties

“…Apart from this, umbelliprenin (150) could attenuate cell migration through the Wnt signaling pathway by decreasing the expression levels of Wnt-2, β-catenin, GSK-3β, p-GSK-3β, survivin, and c-myc [193]. In another study, umbelliprenin was found to induce cytoprotective autophagy by reducing the phosphorylation levels of AKT and mTOR and blocking the Akt signaling pathway [230]. In brief, umbelliprenin (150) could exert its antitumor property by inducing apoptosis and autophagy, inhibiting the cell cycle, and attenuating the migration and invasion of cancer cells.…”

“…Researchers discovered that umbelliprenin (150) could promote apoptosis in tumor cells by annexin V-FITC/PI staining. In the meanwhile, umbelliprenin (150) activated caspase-3, -8, and -9 and the proapoptotic protein Bax and reduced the expression of the antiapoptotic protein Bcl-2, caspase-3, -8, and -9, and the proapoptotic protein Bax and reduced the expression of the antiapoptotic protein Bcl2 [230,231], which promoted apoptosis in the Jurkat T-CLL and Raji B-CLL cell lines in a time-and dosedependent manner [232]. In addition, it could activate the mitochondrial apoptotic pathway and lead to apoptosis of the cancer cells by decreasing the mitochondrial membrane potential, enhancing the P53, P27, P16, and Rb protein expression and diminishing the expression of the proteins of cyclin E, cyclin D, Cdk4, and Cdk6 as well as cell cycle arrest in the G0/G1 phase [233].…”