'Iron-saturated' lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy

Kanwar, Jagat R., Palmano, Kate P., Sun, Xueying, Kanwar, Rupinder K., Gupta, Rita, Haggarty, Neill, Rowan, Angela, Ram, Satyendra and Krissansen, Geoffrey W. 2008, 'Iron-saturated' lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy, Immunology and cell biology, vol. 86, no. 3, pp. 277-288.

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Title 'Iron-saturated' lactoferrin is a potent natural adjuvant for augmenting cancer chemotherapy
Author(s) Kanwar, Jagat R.ORCID iD for Kanwar, Jagat R. orcid.org/0000-0003-3728-9568
Palmano, Kate P.
Sun, Xueying
Kanwar, Rupinder K.
Gupta, Rita
Haggarty, Neill
Rowan, Angela
Ram, Satyendra
Krissansen, Geoffrey W.
Journal name Immunology and cell biology
Volume number 86
Issue number 3
Start page 277
End page 288
Total pages 12
Publisher Nature Publishing Group
Place of publication London, England
Publication date 2008-03
ISSN 0818-9641
Keyword(s) anaemia
bovine lactoferrin
cancer chemotherapy
iron-saturated lactoferrin
tumour eradication
Summary Bovine lactoferrin (bLf), an iron-containing natural defence protein found in bodily secretions, has been reported to inhibit carcinogenesis and the growth of tumours. Here, we investigated whether natural bLf and iron-saturated forms of bLf differ in their ability to augment cancer chemotherapy. bLf was supplemented into the diet of C57BL/6 mice that were subsequently challenged subcutaneously with tumour cells, and treated by chemotherapy. Chemotherapy eradicated large (0.6 cm diameter) EL-4 lymphomas in mice that had been fed iron-saturated bLf (here designated Lf(+)) for 6 weeks prior to chemotherapy, but surprisingly not in mice that were fed lesser iron-saturated forms of bLf, including apo-bLf (4% iron saturated), natural bLf (approximately 15% iron saturated) and 50% iron-saturated bLf. Lf(+)-fed mice bearing either EL-4, Lewis lung carcinoma or B16 melanoma tumours completely rejected their tumours within 3 weeks following a single injection of either paclitaxel, doxorubicin, epirubicin or fluorouracil, whereas mice fed the control diet were resistant to chemotherapy. Lf(+) had to be fed to mice for more than 2 weeks prior to chemotherapy to be wholly effective in eradicating tumours from all mice, suggesting that it acts as a competence factor. It significantly reduced tumour vascularity and blood flow, and increased antitumour cytotoxicity, tumour apoptosis and the infiltration of tumours by leukocytes. Lf(+) bound to the intestinal epithelium and was preferentially taken up within Peyer's patches. It increased the production of Th1 and Th2 cytokines within the intestine and tumour, including TNF, IFN-gamma, as well as nitric oxide that have been reported to sensitize tumours to chemotherapy. Importantly, it restored both red and white peripheral blood cell numbers depleted by chemotherapy, potentially fortifying the mice against cancer. In summary, bLf is a potent natural adjuvant and fortifying agent for augmenting cancer chemotherapy, but needs to be saturated with iron to be effective.
Language eng
Field of Research 111299 Oncology and Carcinogenesis not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
HERDC collection year 2008
Copyright notice ©2008, Australasian Society for Immunology Inc
Persistent URL http://hdl.handle.net/10536/DRO/DU:30018001

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