Abstract
Abstract NexrutineR (Nx) isolated from the bark of Phellodendron amurense is being sold as an anti-inflammatory herbal supplement over the counter in the US. Recent studies from our laboratory demonstrated its potential as an anti-prostatic agent by targeting multiple signaling pathways including Akt/CREB/NFkB/Cyclin D1/Cox-2 both in vitro and in vivo. Given the importance of some of these signaling pathways in multiple cancers, we explored its role in pancreatic cancer (PanCA) using variety of cell lines. Human pancreatic cancer cells that differ in the status of K-Ras (BxPC-3 with wild type K-Ras and Capan-2 with mutant K-Ras), non- tumorigenic HPNE-Ras, MIAPC and ASPC-1 were tested for growth inhibition, apoptosis, necrosis, Cox-2 expression and activity following treatment with Nx. Our data indicate that Nx can significantly inhibit proliferation of these cell lines differentially through induction of apoptosis and necrosis without any significant effect on cell cycle profile. Investigation of molecular mechanism of action identified a role for Jak1 and transcription factors NFkB and Stat3. Western blotting data show that Nx can inhibit the protein levels of pStat3 and Jak1 effectively without influencing the protein levels of total Stat3. Similarly Nx treatment decreased the DNA binding activities of both NFkB and Stat3. Chromatin immunoprecipitation assays revealed the binding of Stat3 to Cox-2 promoter. In addition combining Nx with Gemcitabine (standard of care treatment for PanCA) demonstrated strong synergistic growth inhibitory activity through modulation of Stat3. Overall, the present study unveils a novel interplay between Jak1/Stat3 and NFkB signaling in pancreatic cancer cells. These data further suggest that the targeted disruption of Jak1/Stat3 and NFkB may represent a valid therapeutic approach in this cancer. Supported by NCCAM (APK). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3544. doi:10.1158/1538-7445.AM2011-3544
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
