Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer
Considering the unfavourable response of breast cancer (BC) to treatment, we assessed the therapeutic potential hesperidin in mice bearing 4T1 BC tumours. Anti-tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E-cadherin, VEGF,...
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| Veröffentlicht in: | Journal of cellular and molecular medicine 2023-09, Vol.27 (18), p.2756-2769 |
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| creator | Shakiba, Elham Bazi, Ali Ghasemi, Hamed Gorji, Reza Eshaghi Mehdipour, Seyyed Alireza Nikfar, Banafsheh Rashidi, Mohsen Mirzaei, Sepideh |
| description | Considering the unfavourable response of breast cancer (BC) to treatment, we assessed the therapeutic potential hesperidin in mice bearing 4T1 BC tumours. Anti-tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E-cadherin, VEGF, MMP9, MMP2 and Ki-67, serum measurement of IFNγ and IL-4, and gene expression analysis of CD105, VEGFa, VEGFR2 and COX2. Survival of tumour-bearing mice was the highest in mice receiving a combination of hesperidin and doxorubicin (Dox) (80%) compared to the normal saline (43%), hesperidin 5 (54%), 10 (55.5%), 10 (60.5%) and 40 (66%) mg/kg, and 10 mg/kg Dox-treated (73%) groups (p |
| doi_str_mv | 10.1111/jcmm.17902 |
| format | Article |
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Anti-tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E-cadherin, VEGF, MMP9, MMP2 and Ki-67, serum measurement of IFNγ and IL-4, and gene expression analysis of CD105, VEGFa, VEGFR2 and COX2. Survival of tumour-bearing mice was the highest in mice receiving a combination of hesperidin and doxorubicin (Dox) (80%) compared to the normal saline (43%), hesperidin 5 (54%), 10 (55.5%), 10 (60.5%) and 40 (66%) mg/kg, and 10 mg/kg Dox-treated (73%) groups (p < 0.0001 for all). Compared to the normal saline group, there was a significant elevation in IFNγ level in the animals receiving 20 (p = 0.0026) and 40 (p < 0.001) mg/kg hesperidin, 10 mg/kg Dox (p < 0.001), and combined hesperidin (20 mg/kg) and Dox (10 mg/kg) (p < 0.001). A significant reduction in the gene expression of CD 105 (p = 0.0106), VEGFa (p < 0.0001), VEGFR2 (p < 0.0001), and Cox2 (p = 0.034) and a significant higher pCR score (p = 0.006) were noticed in mice treated with 10 mg/kg Dox + 20 mg/kg hesperidin compared to those treated with 10 mg/kg Dox alone. Immunohistochemical staining showed significant reductions in Ki-67 (p < 0.001) and VEGF (p < 0.001) and a significant elevation in E-cadherin (p = 0.005) in the 10 mg/kg Dox + 20 mg/kg treatment group than in 10 mg/kg Dox alone group. Hesperidin can be considered as a potentially suitable anti-cancer agent for BC that can synergize with other chemotherapeutics.]]></description><identifier>ISSN: 1582-1838</identifier><identifier>EISSN: 1582-4934</identifier><identifier>DOI: 10.1111/jcmm.17902</identifier><identifier>PMID: 37581480</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Angiogenesis ; Antitumor agents ; Breast cancer ; Cancer therapies ; CD105 antigen ; Chemotherapy ; Cyclooxygenase-2 ; Cytotoxicity ; Doxorubicin ; E-cadherin ; Flavonoids ; Gelatinase A ; Gelatinase B ; Gene expression ; Hesperidin ; Histopathology ; Immunohistochemistry ; Metastases ; Metastasis ; Original ; Stem cells ; Survival ; Synergism ; Tumors ; Vascular endothelial growth factor ; γ-Interferon</subject><ispartof>Journal of cellular and molecular medicine, 2023-09, Vol.27 (18), p.2756-2769</ispartof><rights>2023 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><rights>2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2023 The Authors. published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c407t-45bfdc6181a869805a77c8f7e53c2dd1b0c9830684a6a299cf405457c0091b073</citedby><cites>FETCH-LOGICAL-c407t-45bfdc6181a869805a77c8f7e53c2dd1b0c9830684a6a299cf405457c0091b073</cites><orcidid>0000-0001-6164-019X ; 0000-0002-5693-3876</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494297/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10494297/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37581480$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shakiba, Elham</creatorcontrib><creatorcontrib>Bazi, Ali</creatorcontrib><creatorcontrib>Ghasemi, Hamed</creatorcontrib><creatorcontrib>Gorji, Reza Eshaghi</creatorcontrib><creatorcontrib>Mehdipour, Seyyed Alireza</creatorcontrib><creatorcontrib>Nikfar, Banafsheh</creatorcontrib><creatorcontrib>Rashidi, Mohsen</creatorcontrib><creatorcontrib>Mirzaei, Sepideh</creatorcontrib><title>Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer</title><title>Journal of cellular and molecular medicine</title><addtitle>J Cell Mol Med</addtitle><description><![CDATA[Considering the unfavourable response of breast cancer (BC) to treatment, we assessed the therapeutic potential hesperidin in mice bearing 4T1 BC tumours. Anti-tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E-cadherin, VEGF, MMP9, MMP2 and Ki-67, serum measurement of IFNγ and IL-4, and gene expression analysis of CD105, VEGFa, VEGFR2 and COX2. Survival of tumour-bearing mice was the highest in mice receiving a combination of hesperidin and doxorubicin (Dox) (80%) compared to the normal saline (43%), hesperidin 5 (54%), 10 (55.5%), 10 (60.5%) and 40 (66%) mg/kg, and 10 mg/kg Dox-treated (73%) groups (p < 0.0001 for all). Compared to the normal saline group, there was a significant elevation in IFNγ level in the animals receiving 20 (p = 0.0026) and 40 (p < 0.001) mg/kg hesperidin, 10 mg/kg Dox (p < 0.001), and combined hesperidin (20 mg/kg) and Dox (10 mg/kg) (p < 0.001). A significant reduction in the gene expression of CD 105 (p = 0.0106), VEGFa (p < 0.0001), VEGFR2 (p < 0.0001), and Cox2 (p = 0.034) and a significant higher pCR score (p = 0.006) were noticed in mice treated with 10 mg/kg Dox + 20 mg/kg hesperidin compared to those treated with 10 mg/kg Dox alone. Immunohistochemical staining showed significant reductions in Ki-67 (p < 0.001) and VEGF (p < 0.001) and a significant elevation in E-cadherin (p = 0.005) in the 10 mg/kg Dox + 20 mg/kg treatment group than in 10 mg/kg Dox alone group. Hesperidin can be considered as a potentially suitable anti-cancer agent for BC that can synergize with other chemotherapeutics.]]></description><subject>Angiogenesis</subject><subject>Antitumor agents</subject><subject>Breast cancer</subject><subject>Cancer therapies</subject><subject>CD105 antigen</subject><subject>Chemotherapy</subject><subject>Cyclooxygenase-2</subject><subject>Cytotoxicity</subject><subject>Doxorubicin</subject><subject>E-cadherin</subject><subject>Flavonoids</subject><subject>Gelatinase A</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Hesperidin</subject><subject>Histopathology</subject><subject>Immunohistochemistry</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Original</subject><subject>Stem cells</subject><subject>Survival</subject><subject>Synergism</subject><subject>Tumors</subject><subject>Vascular endothelial growth 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Med</addtitle><date>2023-09-01</date><risdate>2023</risdate><volume>27</volume><issue>18</issue><spage>2756</spage><epage>2769</epage><pages>2756-2769</pages><issn>1582-1838</issn><eissn>1582-4934</eissn><abstract><![CDATA[Considering the unfavourable response of breast cancer (BC) to treatment, we assessed the therapeutic potential hesperidin in mice bearing 4T1 BC tumours. Anti-tumour effects were assessed by measuring pathologic complete response (pCR), survival analysis, immunohistochemistry for E-cadherin, VEGF, MMP9, MMP2 and Ki-67, serum measurement of IFNγ and IL-4, and gene expression analysis of CD105, VEGFa, VEGFR2 and COX2. Survival of tumour-bearing mice was the highest in mice receiving a combination of hesperidin and doxorubicin (Dox) (80%) compared to the normal saline (43%), hesperidin 5 (54%), 10 (55.5%), 10 (60.5%) and 40 (66%) mg/kg, and 10 mg/kg Dox-treated (73%) groups (p < 0.0001 for all). Compared to the normal saline group, there was a significant elevation in IFNγ level in the animals receiving 20 (p = 0.0026) and 40 (p < 0.001) mg/kg hesperidin, 10 mg/kg Dox (p < 0.001), and combined hesperidin (20 mg/kg) and Dox (10 mg/kg) (p < 0.001). A significant reduction in the gene expression of CD 105 (p = 0.0106), VEGFa (p < 0.0001), VEGFR2 (p < 0.0001), and Cox2 (p = 0.034) and a significant higher pCR score (p = 0.006) were noticed in mice treated with 10 mg/kg Dox + 20 mg/kg hesperidin compared to those treated with 10 mg/kg Dox alone. Immunohistochemical staining showed significant reductions in Ki-67 (p < 0.001) and VEGF (p < 0.001) and a significant elevation in E-cadherin (p = 0.005) in the 10 mg/kg Dox + 20 mg/kg treatment group than in 10 mg/kg Dox alone group. Hesperidin can be considered as a potentially suitable anti-cancer agent for BC that can synergize with other chemotherapeutics.]]></abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>37581480</pmid><doi>10.1111/jcmm.17902</doi><tpages>14</tpages><orcidid>https://orcid.org/0000-0001-6164-019X</orcidid><orcidid>https://orcid.org/0000-0002-5693-3876</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Angiogenesis Antitumor agents Breast cancer Cancer therapies CD105 antigen Chemotherapy Cyclooxygenase-2 Cytotoxicity Doxorubicin E-cadherin Flavonoids Gelatinase A Gelatinase B Gene expression Hesperidin Histopathology Immunohistochemistry Metastases Metastasis Original Stem cells Survival Synergism Tumors Vascular endothelial growth factor γ-Interferon |
| title | Hesperidin suppressed metastasis, angiogenesis and tumour growth in Balb/c mice model of breast cancer |
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