Ferrichrome (iron-free) is a ferric ionophore for Ustilago sphaerogena, which can serve as a source of iron for the enzyme ferrochelatase [1]. Ferrichrome can induce the adaptive growth of fission yeast on high ammonium medium and restore the iron-dependent pathways to compensate for the dysfunction of the vacuoles induced by ammonium [2]. Ferrichrome has been widely used to induce the iron transporter Arn1p from the endosomal pathway to the plasma membrane pathway in Saccharomyces cerevisiae[3].
In vitro, Ferrichrome treatment for 24 hours significantly inhibited HT29 cells, SKCO1 cells, and SW480 cells, with IC50 values of 0.02µg/ml, 0.34µg/ml, and 0.38µg/ml, respectively[4]. Treatment with 100µg/ml Ferrichrome for 72 hours significantly induced apoptosis in MKN-45 cells, accompanied by an increase in the expression levels of cleaved PARP and cleaved caspase-9[5]. Treatment with 10µg/ml Ferrichrome for 48 hours significantly increased the expression level of DDIT3 mRNA in SW620 cells, stimulated the activity of the JNK signaling pathway, and promoted cell death[6].
In vivo, Ferrichrome treatment via intraperitoneal injection at a dose of 10mg/kg/day for 8days significantly reduced tumor growth in mice with SUIT-2 xenografts[7].
References:
[1] Straka J G, Emergy T. The role of ferrichrome reductase in iron metabolism of Ustilago sphaerogena[J]. Biochimica et Biophysica Acta (BBA)-Enzymology, 1979, 569(2): 277-286.
[2] Chiu P C, Nakamura Y, Nishimura S, et al. Ferrichrome, a fungal-type siderophore, confers high ammonium tolerance to fission yeast[J]. Scientific reports, 2022, 12(1): 17411.
[3] Kim Y, Yun C W, Philpott C C. Ferrichrome induces endosome to plasma membrane cycling of the ferrichrome transporter, Arn1p, in Saccharomyces cerevisiae[J]. The EMBO Journal, 2002, 21(14): 3632-3642.
[4] Iwama T, Fujiya M, Konishi H, et al. Bacteria‐derived ferrichrome inhibits tumor progression in sporadic colorectal neoplasms and colitis‐associated cancer[J]. Cancer cell international, 2021, 21(1): 21.
[5] Ijiri M, Fujiya M, Konishi H, et al. Ferrichrome identified from Lactobacillus casei ATCC334 induces apoptosis through its iron-binding site in gastric cancer cells[J]. Tumor Biology, 2017, 39(6): 1010428317711311.
[6] Konishi H, Fujiya M, Tanaka H, et al. Probiotic-derived ferrichrome inhibits colon cancer progression via JNK-mediated apoptosis[J]. Nature communications, 2016, 7(1): 12365.
[7] Kita A, Fujiya M, Konishi H, et al. Probiotic-derived ferrichrome inhibits the growth of refractory pancreatic cancer cells[J]. International journal of oncology, 2020, 57(3): 721-732.