Sulindac suppresses β-catenin expression in human cancer cells

Abstract

Sulindac has been reported to be effective in suppressing tumor growth through the induction of p21WAF1/cip1 in human, animal models of colon cancer and colon cancer cells. In this study, we treated human breast cancer cell line MCF-7 and lung cancer cell line A549 as well as colon cancer cell line SW620 with sulindac to observe the effects of sulindac in other tissue sites. In all cell lines, proliferation was significantly inhibited by sulindac after 24 and 72 h of treatment. Apoptosis was induced by sulindac in both lung cancer cells and colon cancer cells but was not induced in breast cancer cells. Western blots showed that p21 protein level were induced by sulindac in lung cancer cells and colon cancer cells, but not in breast cancer cells. Most importantly, the suppression of β-catenin, a key mediator of Wnt signaling pathway, was seen in all three cell lines with sulindac administration. Further studies revealed that transcriptional activities of β-catenin were significantly inhibited by sulindac and that the inhibition was sulindac dosage-dependent. The transcriptional targets of β-catenin, c-myc, cyclin D1 and cdk 4 were also dramatically downregulated. In conclusion, our data demonstrated that the efficacy of sulindac in the inhibition of cell proliferation (rather than the induction of apoptosis) might be through the suppression of β-catenin pathway in human cancer cells.

Suppression of Wnt/β-catenin signaling inhibits prostate cancer cell proliferation

“…Thus, we treated PC-3 cells with the non-selective COX inhibitor, sulindac sulfide (Goluboff et al, 1999 & 2001; Narayanan et al, 2004; Han et al, 2008), the COX-2 selective inhibitor, celecoxib (Steinbach et al, 2000; Gupta et al, 2004; Narayanan et al, 2004; Pruthi et al, 2004), and a nitric oxide donating derivative of aspirin, NO-ASA (Kashfi et al, 2002; Rigas, 2007). Fig.…”

“…In the present study, we characterized Wnt/β-catenin signaling in prostate cancer cells, and tested the effects of the nonsteroidal anti-inflammatory drug (NSAID), sulindac sulfide (Goluboff et al, 1999 & 2001; Narayanan et al, 2004; Han et al, 2008), the COX-2 selective inhibitor, celecoxib (Steinbach et al, 2000; Gupta et al, 2004; Narayanan et al, 2004; Pruthi et al, 2004), the nitric oxide-donating aspirin derivative, NO-ASA (Kashfi et al, 2002; Rigas, 2007), and a novel small molecule inhibitor of Wnt/β-catenin signaling, PKF118–310 (Lepourcelet et al, 2004), on prostate cancer cell Wnt/β-catenin signaling and proliferation. Our results suggest that suppression of the Wnt/β-catenin signaling pathway is a potential target for prostate cancer chemoprevention or chemotherapy.…”

MYC and Breast Cancer

“…Sulindac is the most extensively studied nonsteroidal anti-inflammatory drug in the context of chemoprevention. The efficacy of sulindac as an anticancer agent can be attributed to its inhibition of cancer cell proliferation and induction of apoptosis 168. Another β-catenin inhibitor, ICG-001, efficiently inhibits growth of colon carcinoma cells in vitro , in the Min mouse and nude mouse xenograft models of colon cancer,169 which makes it an attractive lead compound for the development of new cancer chemotherapeutics.…”

Combined treatment with vitamin C and sulindac synergistically induces p53- and ROS-dependent apoptosis in human colon cancer cells

“…In addition, celecoxib and curcumin in combination with sulindac have been found to have enhancing anti-cancer effects (Cheng et al, 2013;Vaish et al, 2014). Sulindac and its metabolites have strong antineoplastic activities in colon cancer, which has been reported in several studies (Han et al, 2008;Meyskens et al, 2008;Li et al, 2015;Tinsley et al, 2010). However, the long-term use of sulindac is not recommended as a cancer chemopreventive agent due to its potential severe side effects associated with the inhibition of cyclooxygenases.…”