Hyperoside induces apoptosis and inhibits growth in pancreatic cancer via Bcl-2 family and NF-κB signaling pathway both in vitro and in vivo

Tumour Biol. 2016 Jun;37(6):7345-55. doi: 10.1007/s13277-015-4552-2. Epub 2015 Dec 16.

Abstract

Although advanced surgical operation and chemotherapy have been under taken, pancreatic cancer remains one of the most aggressive and fatal human malignancies with a low 5-year survival rate of less than 5 %. Therefore, novel therapeutic strategies for prevention and remedy are urgently needed in pancreatic cancer. This present research aimed to investigate the anti-cancer effects of hyperoside in human pancreatic cancer cells. Our in vitro results showed that hyperoside suppressed the proliferation and promoted apoptosis of two different human pancreatic cancer cell lines, which correlated with up-regulation of the ratios of Bax/Bcl-2 and Bcl-xL and down-regulation of levels of nuclear factor-κB (NF-κB) and NF-κB's downstream gene products. What's more, using an orthotopic model of human pancreatic cancer, we found that hyperoside also inhibited the tumor growth significantly. Mechanically, these outcomes could also be associated with the up-regulation of the ratios of Bax/Bcl-2 and Bcl-xL and down-regulation of levels of NF-κB and NF-κB's downstream gene products. Collectively, our experiments indicate that hyperoside may be a promising candidate agent for the treatment of pancreatic cancer.

Keywords: Bcl-2 family; Hyperoside; NF-κB; Pancreatic cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Apoptosis / drug effects*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Hypericum / chemistry
  • Mice, Inbred BALB C
  • Mice, Nude
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / physiology
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / pathology*
  • Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
  • Proto-Oncogene Proteins c-bcl-2 / physiology
  • Quercetin / analogs & derivatives*
  • Quercetin / pharmacology
  • Quercetin / therapeutic use
  • Signal Transduction / drug effects*
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / antagonists & inhibitors
  • bcl-2-Associated X Protein / biosynthesis
  • bcl-2-Associated X Protein / genetics
  • bcl-X Protein / antagonists & inhibitors
  • bcl-X Protein / biosynthesis
  • bcl-X Protein / genetics

Substances

  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • BCL2L1 protein, human
  • NF-kappa B
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • bcl-X Protein
  • hyperoside
  • Quercetin