Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer
Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citr...
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| Veröffentlicht in: | Scientific reports 2021-03, Vol.11 (1), p.7121-7121, Article 7121 |
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| description | Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC
50s
and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively. |
| doi_str_mv | 10.1038/s41598-021-86599-z |
| format | Article |
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50s
and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-021-86599-z</identifier><identifier>PMID: 33782546</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/67 ; 631/67/1347 ; 639/638/309 ; Animals ; Aromatase ; Aromatase - metabolism ; Aromatase Inhibitors - pharmacology ; Breast cancer ; Breast Neoplasms - enzymology ; Breast Neoplasms - pathology ; Citrus - chemistry ; Estrogen Receptor Modulators - pharmacology ; Estrogen receptors ; Estrogenic activity ; Estrogens ; Female ; Flavonoids ; Fruits ; Humanities and Social Sciences ; Humans ; Menopause ; Mice ; Molecular modelling ; multidisciplinary ; Naringenin ; Plant Extracts - pharmacology ; Post-menopause ; Quercetin ; Science ; Science (multidisciplinary) ; Solid tumors ; Tumor cell lines ; Xenoestrogens ; Xenograft Model Antitumor Assays</subject><ispartof>Scientific reports, 2021-03, Vol.11 (1), p.7121-7121, Article 7121</ispartof><rights>The Author(s) 2021</rights><rights>The Author(s) 2021. 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><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-62f3d617639be4c80aceb47f71f022caf9bb0472c36bfb6b00c9d53697b39e103</citedby><cites>FETCH-LOGICAL-c540t-62f3d617639be4c80aceb47f71f022caf9bb0472c36bfb6b00c9d53697b39e103</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007834/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8007834/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33782546$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>El-Kersh, Dina M.</creatorcontrib><creatorcontrib>Ezzat, Shahira M.</creatorcontrib><creatorcontrib>Salama, Maha M.</creatorcontrib><creatorcontrib>Mahrous, Engy A.</creatorcontrib><creatorcontrib>Attia, Yasmeen M.</creatorcontrib><creatorcontrib>Ahmed, Mahmoud Salama</creatorcontrib><creatorcontrib>Elmazar, Mohey M.</creatorcontrib><title>Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC
50s
and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.</description><subject>631/67</subject><subject>631/67/1347</subject><subject>639/638/309</subject><subject>Animals</subject><subject>Aromatase</subject><subject>Aromatase - metabolism</subject><subject>Aromatase Inhibitors - pharmacology</subject><subject>Breast cancer</subject><subject>Breast Neoplasms - enzymology</subject><subject>Breast Neoplasms - pathology</subject><subject>Citrus - chemistry</subject><subject>Estrogen Receptor Modulators - pharmacology</subject><subject>Estrogen receptors</subject><subject>Estrogenic activity</subject><subject>Estrogens</subject><subject>Female</subject><subject>Flavonoids</subject><subject>Fruits</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Menopause</subject><subject>Mice</subject><subject>Molecular modelling</subject><subject>multidisciplinary</subject><subject>Naringenin</subject><subject>Plant Extracts - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>El-Kersh, Dina M.</au><au>Ezzat, Shahira M.</au><au>Salama, Maha M.</au><au>Mahrous, Engy A.</au><au>Attia, Yasmeen M.</au><au>Ahmed, Mahmoud Salama</au><au>Elmazar, Mohey M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2021-03-29</date><risdate>2021</risdate><volume>11</volume><issue>1</issue><spage>7121</spage><epage>7121</epage><pages>7121-7121</pages><artnum>7121</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Estrogen signaling is crucial for breast cancer initiation and progression. Endocrine-based therapies comprising estrogen receptor (ER) modulators and aromatase inhibitors remain the mainstay of treatment. This study aimed at investigating the antitumor potential of the most potent compounds in citrus peels on breast cancer by exploring their anti-estrogenic and anti-aromatase activities. The ethanolic extract of different varieties of citrus peels along with eight isolated flavonoids were screened against estrogen-dependent breast cancer cell lines besides normal cells for evaluating their safety profile. Naringenin, naringin and quercetin demonstrated the lowest IC
50s
and were therefore selected for further assays. In silico molecular modeling against ER and aromatase was performed for the three compounds. In vivo estrogenic and anti-estrogenic assays confirmed an anti-estrogenic activity for the isolates. Moreover, naringenin, naringin and quercetin demonstrated in vitro inhibitory potential against aromatase enzyme along with anticancer potential in vivo, as evidenced by decreased tumor volumes. Reduction in aromatase levels in solid tumors was also observed in treated groups. Overall, this study suggests an antitumor potential for naringenin, naringin and quercetin isolated from citrus peels in breast cancer via possible modulation of estrogen signaling and aromatase inhibition suggesting their use in pre- and post-menopausal breast cancer patients, respectively.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>33782546</pmid><doi>10.1038/s41598-021-86599-z</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 631/67 631/67/1347 639/638/309 Animals Aromatase Aromatase - metabolism Aromatase Inhibitors - pharmacology Breast cancer Breast Neoplasms - enzymology Breast Neoplasms - pathology Citrus - chemistry Estrogen Receptor Modulators - pharmacology Estrogen receptors Estrogenic activity Estrogens Female Flavonoids Fruits Humanities and Social Sciences Humans Menopause Mice Molecular modelling multidisciplinary Naringenin Plant Extracts - pharmacology Post-menopause Quercetin Science Science (multidisciplinary) Solid tumors Tumor cell lines Xenoestrogens Xenograft Model Antitumor Assays |
| title | Anti-estrogenic and anti-aromatase activities of citrus peels major compounds in breast cancer |
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