citrinin and Neoplasms

Citrinin (CIT) is a polyketide-derived mycotoxin, which is produced by many fungal strains belonging to the gerena Monascus, Aspergillus, and Penicillium. It has been postulated that mycotoxins have several toxic mechanisms and are potentially used as antineoplastic agents. Therefore, the present study carried out a systematic review, including articles from 1978 to 2022, by collecting evidence in experimental studies of CIT antiplorifactive activity in cancer. The Data indicate that CIT intervenes in important mediators and cell signaling pathways, including MAPKs, ERK1/2, JNK, Bcl-2, BAX, caspases 3,6,7 and 9, p53, p21, PARP cleavage, MDA, reactive oxygen species (ROS) and antioxidant defenses (SOD, CAT, GST and GPX). These factors demonstrate the potential antitumor drug CIT in inducing cell death, reducing DNA repair capacity and inducing cytotoxic and genotoxic effects in cancer cells.

Topics: Animals; Antineoplastic Agents; Cell Death; Cell Lineage; Citrinin; Humans; Neoplasms

Mycotoxin citrinin (CTN), commonly found in food and health supplements, may induce chromosomal instability. In this study, human renal proximal tubule epithelial cells (hRPTECs) that were exposed to CTN (10 and 20 μM) over 3 days exhibited numerical chromosomal aberrations. Short-term (3 days) and long-term (30 days) exposures to CTN significantly promoted mitotic spindle abnormalities, wound healing, cell migration, and anchorage-independent growth in human embryonic kidney 293 (HEK293) cells. Short-term exposure to 10 and 20 μM CTN increased the number of migrated cells on day 10 by 1.7 and 1.9 times, respectively. The number of anchorage-independent colonies increased from 2.2 ± 1.3 to 7.8 ± 0.6 after short-term exposure to 20 μM CTN and from 2.0 ± 1.0 to 12.0 ± 1.2 after long-term exposure. The transcriptomic profiles of CTN-treated HEK293 were subjected to over-representative analysis (ORA), gene set enrichment analysis (GSEA), and Ingenuity pathway analysis (IPA). Short-term exposure to CTN promoted the RTK/KRAS/RAF/MAPK cascade, while long-term exposure altered the extracellular matrix organization. Both short- and long-term CTN exposure activated cancer and cell cycle-related signaling pathways. These results demonstrate the carcinogenic potential of CTN in human cells and provide valuable insights into the cancer risk associated with CTN.

Topics: Carcinogens; Citrinin; HEK293 Cells; Humans; Kidney; Neoplasms

Many mould strains, in particular Aspergillus and/or Penicillium, are able to develop on olive and produce ochratoxin A (OTA) and/or citrinin (CIT) and/or aflatoxin B (AFB) after harvest, during drying and storage of olives. The development of fungi on olives is responsible for the reduction of nutritional quality of olive because they can disturb the synthesis of the fatty acids. OTA, CIT and AFB are particularly dangerous for health, inducing cancer of urinary tracts or liver carcinoma. In this study, ten olive samples bought at retailer and at supermarket in Morocco were analyzed for their OTA, CIT and AFB contents. These three mycotoxins were extracted simultaneously by a method based on solvent partition validated in-house, then separated by HPLC coupled to a fluorescence detector. All olive samples contain OTA ranging from LOQ to 1.02 microg/kg. Respectively, 50 and 25% from retailer and supermarket samples were contaminated by more than 0.65 microg/kg. In addition, 80% of olive samples contained CIT above LOD, and 100% of olive tested contained AFB above 0.5 microg/kg. As simultaneous presence of these toxins increases toxic risks, it is thus essential to have a good control of the conservation of olives after harvest.

Topics: Aflatoxin B1; Animals; Chromatography, High Pressure Liquid; Citrinin; Food Contamination; Fruit; Humans; Kidney Diseases; Morocco; Neoplasms; Ochratoxins; Olea; Reproducibility of Results; Swine