Berberine and Curcumin Target Survivin and STAT3 in Gastric Cancer Cells and Synergize Actions of Standard Chemotherapeutic 5-Fluorouracil

Abstract

Aberrantly expressed survivin and STAT3 signaling have emerged as major determinants of chemoresistance in gastric cancer. We evaluated effects of potent herbal derivatives curcumin, berberine, and quercetin on STAT3 signaling, survivin expression, and response to 5-fluorouracil (5-FU) treatment in gastric cancer cells (AGS). Cytotoxic and inhibitory effects of berberine, curcumin, and quercetin alone or in combination with 5-FU were examined by MTT assay, and their effect on survivin, STAT3, and the phosphorylated active STAT3 (pSTAT3) expression was examined by western blotting. Effect of these herbal derivatives on STAT3 DNA binding activity was measured by electrophoretic mobility shift assay. Curcumin, berberine, and quercetin effectively downregulated pSTAT3 levels, survivin expression, and gastric cancer cells viability in a dose-dependent manner (with corresponding IC50 values of 40.3μM, 29.2μM and 37.5μM, respectively). Berberine was more effective in inhibiting survivin expression as compared to other herbal agents. 5-FU in combination with berberine or curcumin showed a synergistic inhibition of survivin and STAT3 level resulting in enhanced cell death in gastric cancer cells. Overall, our data suggest use of berberine and curcumin as adjunct therapeutics to overcome chemoresistance during treatment of gastric malignancies.

Chromatin-Bound Oxidized α-Synuclein Causes Strand Breaks in Neuronal Genomes in in vitro Models of Parkinson’s Disease

“…Flow-cytometric analysis of apoptotic cell death was performed as indicated earlier [44]. Briefly, cells were harvested, washed with PBS, and incubated with fluorescein isothiocynate (FITC) conjugated Annexin V and propidium iodide (PI) according to the instruction of Annexin V apoptosis detection kit.…”

Curcumin sensitizes human gastric cancer cells to 5-fluorouracil through inhibition of the NFκB survival-signaling pathway

“…It has been found to have antitumor, anti-inflammatory, and apoptotic properties both in vitro and in vivo 14–16. Studies have demonstrated that curcumin has the potential to be combined with chemotherapeutics for GC 17,18. These reports focused mainly on the role of curcumin in resistant GC cells through the activation of survivin and STAT3 signaling.…”

Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction

“…Taken together, these data indicate that Curcumin reduces the expression of MTA1 gene through upregulation of miR-30c-5p in Paclitaxel-resistant NSCLC cells. Since Curcumin has been reported to regulate signaling molecules and transcriptional factors, [15][16][17] further studies can be done to explore which signaling molecule and/or transcriptional factor is required for Curcumin-increased miR-30c-5p expression in Paclitaxel-resistant NSCLC cells.…”

“…[11][12][13][14] As an anticancer agent, Curcumin has been demonstrated to regulate transcriptional factors, signaling molecules, and microRNAs (miRNAs), such as signal transducer and activator of transcription 3 (STAT3), activation protein 1 (AP-1), Forkhead box O1 (FOXO1), nuclear factor kappa B (NF-κB), Akt, reactive oxygen species (ROS), miR-208, and miR-21. [14][15][16][17][18] Our current study revealed that Curcumin could increase the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel in vitro. Further studies need to be done to explore the potential mechanism by which Curcumin enhances the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel.…”