Dietary Crocin is Protective in Pancreatic Cancer while Reducing Radiation-Induced Hepatic Oxidative Damage

Nutrients. 2020 Jun 26;12(6):1901. doi: 10.3390/nu12061901.

Abstract

Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.

Keywords: apoptosis; cell cycle; crocin; hepatic injury; pancreatic cancer; radiation.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic
  • Apoptosis / drug effects
  • Carotenoids / therapeutic use*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Crocus / chemistry
  • Cytochromes c / metabolism
  • Female
  • Humans
  • Lipid Peroxidation / drug effects
  • Liver Diseases / etiology*
  • Liver Diseases / prevention & control*
  • Mice
  • Mice, Nude
  • Pancreatic Neoplasms / drug therapy*
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / radiotherapy*
  • Radiation Injuries / prevention & control*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Transcriptome
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Cell Cycle Proteins
  • Carotenoids
  • crocin
  • Cytochromes c