“Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice
<p>Abstract</p> <p>Background</p> <p>Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine la...
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| Format: | Article |
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BMC
2012-12-01
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| Series: | BMC Cancer |
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| Online Access: | http://www.biomedcentral.com/1471-2407/12/591 |
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| author | Sun Xueying Jiang Ruohan Przepiorski Aneta Reddy Shiva Palmano Kate P Krissansen Geoffrey W |
| author_facet | Sun Xueying Jiang Ruohan Przepiorski Aneta Reddy Shiva Palmano Kate P Krissansen Geoffrey W |
| author_sort | Sun Xueying |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers.</p> <p>Methods</p> <p>In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg) were fed an Fe-Lf supplemented diet (5 g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed.</p> <p>Results</p> <p>Tamoxifen weakly (IC<sub>50</sub> ~ 8 μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations <it>in vitro</it>. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all <it>P</it> < 0.001), respectively, compared to untreated controls. The combination therapy was significantly (all <it>P</it> < 0.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors.</p> <p>Conclusions</p> <p>The results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors.</p> |
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| spelling | doaj.art-5756d70f0b2143f5af18504850cc5ab32022-12-22T03:24:46ZengBMCBMC Cancer1471-24072012-12-0112159110.1186/1471-2407-12-591“Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in miceSun XueyingJiang RuohanPrzepiorski AnetaReddy ShivaPalmano Kate PKrissansen Geoffrey W<p>Abstract</p> <p>Background</p> <p>Tamoxifen is used in hormone therapy for estrogen-receptor (ER)-positive breast cancer, but also has chemopreventative effects against ER-negative breast cancers. This study sought to investigate whether oral iron-saturated bovine lactoferrin (Fe-Lf), a natural product which enhances chemotherapy, could improve the chemotherapeutic effects of tamoxifen in the treatment of ER-negative breast cancers.</p> <p>Methods</p> <p>In a model of breast cancer prevention, female Balb/c mice treated with tamoxifen (5 mg/Kg) were fed an Fe-Lf supplemented diet (5 g/Kg diet) or the base diet. At week 2, 4T1 mammary carcinoma cells were injected into an inguinal mammary fat pad. In a model of breast cancer treatment, tamoxifen treatment was not started until two weeks following tumor cell injection. Tumor growth, metastasis, body weight, and levels of interleukin 18 (IL-18) and interferon γ (IFN-γ) were analyzed.</p> <p>Results</p> <p>Tamoxifen weakly (IC<sub>50</sub> ~ 8 μM) inhibited the proliferation of 4T1 cells at pharmacological concentrations <it>in vitro</it>. In the tumor prevention study, a Fe-Lf diet in combination with tamoxifen caused a 4 day delay in tumor formation, and significantly inhibited tumor growth and metastasis to the liver and lung by 48, 58, and 66% (all <it>P</it> < 0.001), respectively, compared to untreated controls. The combination therapy was significantly (all <it>P</it> < 0.05) more effective than the respective monotherapies. Oral Fe-Lf attenuated the loss of body weight caused by tamoxifen and cancer cachexia. It prevented tamoxifen-induced reductions in serum levels of IL-18 and IFN-γ, and intestinal cells expressing IL-18 and IFN-γ. It increased the levels of Lf in leukocytes residing in gut-associated lymphoid tissues. B, T and Natural killer (NK) cells containing high levels of Lf were identified in 4T1 tumors, suggesting they had migrated from the intestine. Similar effects of Fe-Lf and tamoxifen on tumor cell viability were seen in the treatment of established tumors.</p> <p>Conclusions</p> <p>The results indicate that Fe-Lf is a potent natural adjuvant capable of augmenting the chemotherapeutic activity of tamoxifen. It could have application in delaying relapse in tamoxifen-treated breast cancer patients who are at risk of developing ER-negative tumors.</p>http://www.biomedcentral.com/1471-2407/12/591Breast cancerIron-saturated lactoferrinTamoxifenImmune enhancementMice |
| spellingShingle | Sun Xueying Jiang Ruohan Przepiorski Aneta Reddy Shiva Palmano Kate P Krissansen Geoffrey W “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice BMC Cancer Breast cancer Iron-saturated lactoferrin Tamoxifen Immune enhancement Mice |
| title | “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice |
| title_full | “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice |
| title_fullStr | “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice |
| title_full_unstemmed | “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice |
| title_short | “Iron-saturated” bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal-like breast cancer in mice |
| title_sort | iron saturated bovine lactoferrin improves the chemotherapeutic effects of tamoxifen in the treatment of basal like breast cancer in mice |
| topic | Breast cancer Iron-saturated lactoferrin Tamoxifen Immune enhancement Mice |
| url | http://www.biomedcentral.com/1471-2407/12/591 |
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