Cytoprotective, Antiproliferative, and Anti-Oxidant Potential of the Hydroethanolic Extract of Fridericia chica Leaves on Human Cancer Cell Lines Exposed to α- and β-Zearalenol

Toxins (Basel). 2023 Jan 3;15(1):36. doi: 10.3390/toxins15010036.

Abstract

Fridericia chica (Bignoniaceae) is a Colombian Caribbean plant with numerous health benefits, including properties such as wound healing, immune system stimulation, and antioxidant capacity, among others. Mycotoxins alpha-zearalenol (α-ZEL) and beta-zearalenol (β-ZEL) are phase I metabolites of zearalenone, a natural product involved in endocrine disruption and cell proliferation processes. This study aimed to investigate the cytotoxic potential of the hydroethanolic extract of F. chica leaves (HEFc) and determine their protective effects against proliferation induced by α-ZEL and β-ZEL on human hepatoma HepG2, lung cancer Calu-1, and primary normal human epidermal keratinocytes, neonatal (HEKn). The cytotoxicity of HEFc was measured in a range from 4 to 1000 µg/mL and from 0.4 to 100 μM for both α-ZEL and β-ZEL. Cell production of intracellular ROS was monitored using the H2-DCFDA probe. The cells exposed to HEFc presented IC50 of 128, 249, and 602 µg/mL for the HepG2, Calu-1, and HEKn cells, respectively. A greater selectivity was seen in HepG2 cells [selectivity index (SI) = 3.5] than in Calu-1 cells (SI = 2.4). Cells treated with mycotoxins remained viable during the first day, and cell proliferation increased at low tested concentrations (0.4-6.3 µM) in all three cell lines. However, after 48 h treatment, cells exposed to 50 and 100 µM of α-ZEL and β-ZEL displayed decreased viability. HEFc at 16 µg/mL was able to give some protection against cytotoxicity induced by high concentrations of β-ZEL in HepG2, reducing also cell proliferation elicited at low levels of α-ZEL and β-ZEL. ROS production was not observed in cells treated with this HEFc concentration; however, it prevented ROS formation induced by treatment with 50 µM α-ZEL or β-ZEL. In summary, HEFc isolated from plants grown in northern Colombia displayed promising results against cell proliferation and oxidative stress caused by mycotoxins.

Keywords: ROS; cytotoxicity; mycotoxins; plant extracts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology
  • Bignoniaceae*
  • Cell Line
  • Humans
  • Infant, Newborn
  • Lung Neoplasms*
  • Mycotoxins* / toxicity
  • Reactive Oxygen Species
  • Zearalenone* / toxicity

Substances

  • zearalenol
  • Antioxidants
  • Reactive Oxygen Species
  • Zearalenone
  • Mycotoxins

Grants and funding

The authors thank the Ministry of Science, Technology and Innovation (Minciencias), the Ministry of Education, the Ministry of Industry, Commerce and Tourism, and ICETEX, Programme Ecosistema Científico-Colombia Científica, from the Francisco José de Caldas Fund (Grant RC-FP44842-212-2018); Spanish Ministry of Science and Innovation (PID2020-115871RB-I00); Minciencias (Grant: 466-2021); Minciencias, Sistema General de Regalías de Colombia (BPIN 2020000100093-2020, Gobernación de Bolívar).