Baicalein flavone targets cisplatin resistant human pancreatic cancer cells via inducing S-phase cell cycle arrest, inhibition of cell migration and invasion, caspase activation and mitochondrial-dependent apoptosis

J BUON. 2020 Jul-Aug;25(4):1947-1953.

Abstract

Purpose: Pancreatic cancer (PC) is a lethal disease of the alimentary system and is ranked 4th in cancer-related deaths in United States. PC has a poor prognosis and limited therapeutic options. The main purpose of the current study was to demonstrate the anticancer effects of the naturally occurring Baicalein flavone in human cisplatin-resistant pancreatic carcinoma cell line CAPAN-2.

Methods: Cell viability was examined via MTT cell proliferative assay. Mitochondrial-mediated apoptosis was examined through DAPI and annexin V/propidium iodide (PI) staining using fluorescence microscopy along with estimation of apoptosis-related protein expressions like caspase-3, Bax, Bcl-2 for which western blot was used. Next, wound-healing and transwell assays were performed to find out the effects of Baicalein on cell migration and invasion, respectively.

Results: The results showed that Baicalein induced dose-dependent and selective anticancer effects in CAPAN-2 PC cancer cells with much less cytotoxicity to normal HTRET-HPNE cells. The antiproliferative effects of Baicalein were due to apoptosis induction as the number of apoptotic cells increased on increasing doses of the test molecule. Western blotting analysis revealed that the expressions of caspase-3 and Bcl-2 were decreased and Bax was increased. The test molecule also induced S-phase cell cycle arrest in PC cells with decreasing the cyclin-B1 expressions. Cell migration and invasion analysis revealed that Baicalein induced dose-dependent suppression in migration and invasion of CAPAN-2 PC cell line.

Conclusion: Baicalein is a potential anticancer agent against PC cells and can be considered for PC systemic therapy provided more toxicological and in vivo studies are carried out.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Apoptosis
  • Caspases / metabolism*
  • Cell Cycle Checkpoints / physiology*
  • Cell Movement / physiology*
  • Cisplatin / pharmacology
  • Cisplatin / therapeutic use*
  • Flavanones / pharmacology
  • Flavanones / therapeutic use*
  • Humans
  • Mitochondria / metabolism*
  • Neoplasm Invasiveness / physiopathology*
  • Pancreatic Neoplasms / drug therapy*
  • S Phase / physiology*

Substances

  • Antineoplastic Agents
  • Antioxidants
  • Flavanones
  • baicalein
  • Caspases
  • Cisplatin