A novel synergistic effect of iron depletion on anti-angiogenic cancer
therapy.
Ohara T, Noma K, Fujiwara T
Int J Cancer 2012 Nov 15

Abstract
Iron is an essential element for both normal and cancer cells in
humans. Treatment to reduce iron levels has been shown to suppress
tumor growth in vivo.
However, iron depletion mono-therapy by iron decreased treatment has
not been thought to be superior to ordinary chemotherapy and is not
part of the standard therapeutic strategy for the treatment of
cancer.
Iron depletion is also known to reduce serum hemoglobin and oxygen
supply to the tissue, which indicates that iron depletion may induce
angiogenesis.
Therefore, we hypothesized that iron depletion with anti-angiogenic
therapy can have a novel therapeutic effect in the treatment of
cancer.
Human non-small cell carcinoma cell lines A549 and H1299 were used in
this study.
An iron-deficient diet and an iron chelator were used to simulate an
iron-depleted condition.
The anti-tumor effects of iron-depletion and anti-angiogenic therapy
were determined on A549 xenograft mice.
The iron-depleted condition produced by an iron-deficient diet
suppressed tumor growth.
Tumor tissue from the iron-deficient diet group showed that cancer
cell proliferation was suppressed and hypoxia was induced.
Microvessel density of this group was increased which suggested that
the iron-depleted condition induced angiogenesis.
Bevacizumab administration had a synergetic effect on inhibiting the
tumor growth on Day 39. An iron-depleted condition inhibited cancer
cell proliferation and reciprocally induced angiogenesis.
Bevacizumab synergistically enhanced the iron-depleted anti-tumor
effect. Treatment to deplete iron levels combined with anti-angiogenic
therapy could induce a novel therapeutic effect in the treatment of
cancer.

© 2012 Wiley Periodicals, Inc.


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