An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines

Kyriaki Hatziagapiou; Olti Nikola; Sofia Marka; Eleni Koniari; Eleni Kakouri; Maria-Eleftheria Zografaki; Sophie S Mavrikou; Charalabos Kanakis; Emmanouil Flemetakis; George P Chrousos; Spyridon Kintzios; George I Lambrou; Christina Kanaka-Gantenbein; Petros A Tarantilis

doi:10.3390/antiox11061074

An In Vitro Study of Saffron Carotenoids: The Effect of Crocin Extracts and Dimethylcrocetin on Cancer Cell Lines

Antioxidants (Basel). 2022 May 28;11(6):1074. doi: 10.3390/antiox11061074.

Authors

Affiliations

¹ Choremeio Research Laboratory, First Department of Pediatrics, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece.
² Physiotherapy Department, Faculty of Health and Care Sciences, State University of West Attica, Agiou Spiridonos 28, Egaleo, 12243 Athens, Greece.
³ Laboratory of Cell Technology, Department of Biotechnology, Agricultural University of Athens, EU-CONEXUS European University, 11855 Athens, Greece.
⁴ University Research Institute of Maternal and Child Health & Precision Medicine, UNESCO Chair on Adolescent Health Care, National and Kapodistrian University of Athens, Thivon & Levadeias 8, 11527 Athens, Greece.
⁵ Laboratory of Chemistry, Department of Food Science & Human Nutrition, School of Food Biotechnology and Development, Agricultural University of Athens, EU-CONEXUS European University, 11855 Athens, Greece.
⁶ Laboratory of Molecular Biology, Department of Biotechnology, Agricultural University of Athens, EU-CONEXUS European University, 11855 Athens, Greece.

Abstract

Crocus sativus L. has various pharmacological properties, known for over 3600 years. These properties are attributed mainly to biologically active substances, which belong to the terpenoid group and include crocins, picrocrocin and safranal. The aim of the current work was to examine the effects of crocins (CRCs) and their methyl ester derivate dimethylcrocetin (DMCRT) on glioblastoma and rhabdomyosarcoma cell lines, in terms of cytotoxicity and gene expression, implicated in proapoptotic and cell survival pathways. Cell cytotoxicity was assessed with Alamar Blue fluorescence assay after treatment with saffron carotenoids for 24, 48 and 72 h and concentrations ranging from 22.85 to 0.18 mg/mL for CRCs and 11.43 to 0.09 mg/mL for DMCRT. In addition, BAX, BID, BCL2, MYCN, SOD1, and GSTM1 gene expression was studied by qRT-PCR analysis. Both compounds demonstrated cytotoxic effects against glioblastoma and rhabdomyosarcoma cell lines, in a dose- and time-dependent manner. They induced apoptosis, via BAX and BID upregulation, MYCN and BCL-2, SOD1, GSTM1 downregulation. The current research denotes the possible anticancer properties of saffron carotenoids, which are considered safe phytochemicals, already tested in clinical trials for their health promoting properties.

Keywords: crocins (CRCs); cytotoxicity; dimethylocrocetin (DMCRT); glioblastoma (GBM); rhabdomyosarcoma; saffron.

Grants and funding

MIS 5048464/Operational Program "Human Resources Development, Education and Lifelong Learning 2014-2020" and the Program encoded EDBM103, titled "Support for researchers with an emphasis on young researchers-cycle B"