posted on 2023-11-21, 17:07authored byJui-Feng Tsai, Ting-Shuan Wu, Ying-Tzu Huang, Wan-Ju Lin, Feng-Yih Yu, Biing-Hui Liu
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.