Anti-cancer impact of Hypericin in B-CPAP cells: Extrinsic caspase dependent apoptosis induction and metastasis obstruction

Eur J Pharmacol. 2021 Nov 5:910:174454. doi: 10.1016/j.ejphar.2021.174454. Epub 2021 Aug 27.

Abstract

Thyroid cancer is the most common type of endocrine-related cancer. According to the literature, its incidence is not very high, but its rate increasing especially in developed countries. With this regard, finding approaches to prevent, and exert anti-tumor activity with the least side effects on the normal cells at the next step after diagnosis is demanded. Herbal medicine is a branch of integrative oncology that seems to be a practically beneficial goddess for cancer treatment in many cases. Here we utilized Hypericin (HYP) to investigate its anti-tumor (apoptotic and anti-metastatic) activity on B-CPAP (a thyroid cancer cell line) and cytotoxicity on TPC-1 (thyroid cancer cell line with wild type TP53) cell lines. To assess whether HYP may exert preventive and anti-tumor effects and does not have a potential side effect, we dubbed the experiments on the fibroblast cells (as a normal cell line). Cytotoxicity and kind of cellular death were examined by MTT and AnnexinV/PI respectively. Extrinsic/intrinsic apoptosis pathway induction was clarified by western blotting on pro/cleaved caspases 9, 8, and 3. According to our data HYP induces an extrinsic apoptosis pathway and no other types (necroptosis, necrosis, etc.) in B-CPAP cells. Moreover, CDH1 mRNA expression calculated to be up-regulated, and that of LGALS3 down-regulated in the B-CPAP cell line after treatment. Besides tumor cytotoxic activity, we suggest that HYP impedes with invasion and/or metastasis process.

Keywords: Apoptosis; B-CPAP; Hypericin; Metastasis; Thyroid cancer.

MeSH terms

  • Anthracenes / pharmacology*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Caspase 3 / metabolism
  • Caspase 8 / metabolism
  • Caspase 9 / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Fibroblasts / drug effects
  • Fibroblasts / metabolism
  • Humans
  • Inhibitory Concentration 50
  • Neoplasm Metastasis
  • Perylene / analogs & derivatives*
  • Perylene / pharmacology
  • Signal Transduction / drug effects
  • Thyroid Neoplasms / drug therapy*
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology

Substances

  • Anthracenes
  • Antineoplastic Agents
  • Perylene
  • hypericin
  • CASP3 protein, human
  • CASP8 protein, human
  • CASP9 protein, human
  • Caspase 3
  • Caspase 8
  • Caspase 9