Avicenna Journal of Phytomedicine

Avicenna Journal of Phytomedicine

Enhanced bioavailability and cytotoxicity of disodium crocetinate over crocin in HCT-116 colorectal cancer cells: evidence from bioinformatics and experiments

Articles in Press

Document Type : Original Research Article

Authors
Mahmoud Hassanpour 1
Mehran Ghaemi 2
Mahmoud Aminlari 1
Mohammad Reza Saberi 3
Salman AbdolahRamazani 3
1 Department of Biochemistry, School of Veterinary Medicine, Shiraz University, Shiraz, Iran
2 Department of Pathobiology, School of Veterinary Medicine, Shiraz University, Shiraz, Iran Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
3 Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
10.22038/ajp.2026.27944
Abstract
Objective: Colorectal cancer (CRC) remains a highly aggressive malignancy. This study directly compared the effects of crocin and disodium crocetinate (DSC) on human CRC HCT-116 cells.
Materials and methods: Crocin was converted to water-soluble DSC using alkali-catalyzed hydrolysis. Cells were treated with varying concentrations of crocin or DSC to assess viability. SYBR green quantitative real-time RT-PCR analyzed transcriptional modulation of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9). Molecular docking with MOE software investigated binding modes of crocin and crocetin to the ETS translocation variant 4 (ETV4) protein.
Results: DSC induced a substantially stronger cytotoxic response than crocin, achieving an IC₅₀ of 0.4 mM. In contrast, crocin did not reach 50% growth inhibition within the tested range, resulting in a non-experimentally measurable IC₅₀ estimate of 3.3 mM. DSC treatment led to markedly greater downregulation of both MMP2 and MMP9 compared to crocin, consistent with prior work linking crocetin to inhibition of MAPK, NF-κB, and PI3K/Akt axes upstream of MMP transcription. Docking analysis revealed that crocetin physicochemical profile is vastly more aligned with ETV4 modulation.
Conclusion: Collectively, DSC constitutes a more potent inhibitor of CRC growth and metastatic potential than crocin, offering a mechanistically substantiated candidate for future preclinical evaluation. Crocin and crocetin act through ETV4 as a novel therapeutic target in the MAPK pathway.
Keywords
Colorectal Neoplasms Crocin Crocetin Disodium crocetinate MMPs ETV4 HCT
116 cells
Subjects
Avicenna Journal of Phytomedicine

Articles in Press, Accepted Manuscript
Available Online from 20 June 2026