Table 1 Protocol based on Deferasirox in cancer therapy

Leukemia

CALM-AF10 leukemia cells are susceptible to the cytotoxic effects of DFX (5 μM). However, oral chelation induced by DFX (i.p. 33 mg/kg/day) is not tolerable to leukemic mice and resulted in shortened overall survival.

[32]

DFX (10 to 60 μM) shows antiproliferative activity as well as cytotoxicity toward several myeloma cells (RPMI 8226, U266 and NCIH929). Mechanisms involved are induced autophagy and repression of mTOR signaling.

[33]

DFX (20–30 mg/kg/day) synergizes with vitamin D to promote monocyte differentiation and to increase overall survival in elderly patients (≥65 years) with acute myeloid leukemia.

[34]

DFX (12.5 to 100 μM) reduces viability of murine leukemic cells (EL4 and L1210) and induces apoptosis. Mice bearing L1210 leukemic cells show longer survival than other groups when treated with DFX (p.o. 20 mg/kg/day) with a tumor size smaller.

[35]

Iron chelation therapy with DFX induces complete remission in a patient with chemotherapy-resistant acute monocytic leukemia

[36]

DFX (5 to 50 μM) induces apoptosis in myeloid leukemia cells by targeting caspase.

[37]

DFX (50 μM) induces apoptosis and inhibits NFKB activity in K562 leukemia cells independently of iron deprivation.

[38]

DFX (17 to 50 μM) inhibits proliferation in human myeloid leukemia cell lines (K562, U937, and HL60). Molecular mechanism responsible for antiproliferative effects involved REDD1/mTOR pathway.

[39]

Esophageal adeno-carcinoma (OAC)

Iron has been shown to potentiate tumorigenesis in OAC but OAC has traditionally been associated with iron deficiency anemia. However, patients with OAC could be considered as candidates for a clinical trial of iron chelation therapy.

[40]

DFX (10 to 40 μM) reduces cellular viability and proliferation of esophageal tumor cell lines (OE33, OE19 and 0E21) and is able to overcome cisplatin resistance. In human xenograft models, DFX (p.o. 20 mg/kg/day) is able to suppress tumor growth, which was associated with decreased tumor iron levels.

[41]

Lymphoma

DFX (8 to 32 μM) exhibits antitumoral activity against mantle cell lymphoma (HBL-2, Granta-519, Jeko-1). DFX induces apoptosis through caspase-3 activation, down-regulates cyclin D1 and inhibits its related signals, which leads to a G1-S cell cycle arrest.

[42]

DFX (20 to 100 μM) has dose-dependent cytotoxic effects on human malignant lymphoma cell lines (NCI H28:N78, Ramos, and Jiyoye) with increased sub-G1 portion and apoptosis.

[43]

Lung Cancer

DFX (10 μM) has antiproliferative effect against DMS-53 lung cancer cells and inhibits DMS-53 xenograft growth in nude mice (p.o. 20 mg/kg/day). Mechanisms involved are increased expression of NDRG1 and CIP1/WAF1 and decreased cyclin D1 levels.

[44]

Colorectal cancer

DFX (50 μM) inhibits Wnt signaling in colorectal cancer cells (SW480 and DLD-1) and represses cell proliferation in parallel of the induction of an iron chelation gene signature.

[45]

Liver cancer

DFX (10 to 100 μM) represses proliferation of human hepatocarcinoma cells (HepaRG).

[46]

In rat (FAO) and human (HUH7) hepatoma cell lines, DFX (10 to 100 μM) decreases cell viability, DNA replication and the number of the cells in G2-M phase and induces apoptosis. Moreover, DFX inhibits polyamine biosynthesis.

[47]

DFX (10 to 100 μM) induces a cell cycle blockade in G0–G1, decreases cell viability, inhibits DNA replication and induces DNA fragmentation in the human hepatoma cell line HUH7. Importantly, a higher concentration of DFX is necessary to induce cytotoxicity in primary human hepatocyte cultures.

[48]