Dauricine suppresses the growth of pancreatic cancer in�vivo by modulating the Hedgehog signaling pathway

Abstract

Pancreatic cancer is a highly malignant cancer associated with high expression levels of sonic hedgehog signaling molecule (Shh), patched 1 (Ptch1), smoothened frizzled class receptor (Smo) and glioma-associated oncogene family zinc finger 1 (Gli1) in the hedgehog (Hh) signaling pathway. Inhibition of the Hh signaling pathway is a potential therapeutic target for pancreatic cancer. The aim of the present study was to investigate the effects of dauricine in a pancreatic cancer BxPC-3 ×enograft animal model and examine the underlying molecular mechanisms through Hh signaling pathway. High-and low-dose dauricine treatment significantly suppressed tumor growth with no concomitant effect on the spleen index. In addition, dauricine induced apoptosis and cell cycle arrest in pancreatic cancer BxPC-3 cells. The inhibitory effects of dauricine on pancreatic cancer may be mediated by the suppression of the Hh signaling pathway, as indicated by the decreases in the gene and protein expression levels of Shh, Ptch1, Smo and Gli1. The effects of dauricine were similar to those of 5-fluorouracil. Dauricine, a naturally occurring alkaloid, may be a potential anticancer agent for the treatment of pancreatic cancer.

Dauricine Protects from LPS-Induced Bone Loss via the ROS/PP2A/NF-κB Axis in Osteoclasts

“…However, it is plausible that DAC did not confer any protection from bone loss at a higher dose due to reduced bone formation. DAC has been demonstrated to be therapeutically effective in rodents at 5–10 mg/kg for inflammatory processes induced by ischemia/reperfusion [ 18 ], 5–20 mg/kg to protect from cecal ligation and puncture-induced acute lung injury [ 19 ], and 6–12 mg/kg to suppress pancreatic tumor growth [ 34 ]. In vitro inhibition of NF-kB has been reported to be within the ranges of 1–10 μM and 5–40 μM in macrophages [ 19 ] and colon cancer cells [ 20 ], respectively.…”

Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways

“…It has potent antitumor activity, including the induction of apoptosis and overcoming drug resistance of tumor cells. Dauricine was found to reduce the survival of renal cell carcinoma (RCC) cells and induced cell cycle arrest in the G0/G1 phase and induced apoptosis through the intrinsic pathway [ 173 ]. Among these mechanisms, the former was associated with the downregulation of cyclin D1, CDK2, and CDK4 and the upregulation of p21.…”

Isoquinolines alkaloids and cancer metabolism: Pathways and targets to novel chemotherapy

“…Dauricine presents antitumoral activity by inducing apoptosis in pancreatic, renal, and cervical cancer cell lines (Table 1) (Zhang et al, 2018(Zhang et al, , 2019Zhou et al, 2019). In renal cancer, dauricine increased proapoptotic proteins expression, increasing caspase 3 and 9 activities and inhibiting PI3K-AKT signaling pathway (Zhang et al, 2018).…”