Hydrogen peroxide overproduced in breast cancer cells can serve as an anticancer prodrug generating apoptosis-stimulating hydroxyl radicals under the effect of tamoxifen-ferrocene conjugate
A new approach to the treatment of cancer is suggested, based on the innate overproduction of hydrogen peroxide in cancer cells. Hydrogen peroxide serves as a prodrug in the presence of transition metal ions, such as iron delivered by ferrocene. Under the effect of ferrocene, hydrogen peroxide is sp...
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| Veröffentlicht in: | Journal of pharmacy and pharmacology 2007-11, Vol.59 (11), p.1549-1553 |
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| container_issue | 11 |
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| container_title | Journal of pharmacy and pharmacology |
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| creator | Wlassoff, Wjatschesslaw A. Albright, Craig D. Sivashinski, Michael S. Ivanova, Anastasia Appelbaum, Jacob G. Salganik, Rudolph I. |
| description | A new approach to the treatment of cancer is suggested, based on the innate overproduction of hydrogen peroxide in cancer cells. Hydrogen peroxide serves as a prodrug in the presence of transition metal ions, such as iron delivered by ferrocene. Under the effect of ferrocene, hydrogen peroxide is split into hydroxyl anions and highly reactive hydroxyl radicals. The latter cause oxidative DNA damage, which induces apoptosis, leading to elimination of cancer cells. Tamoxifen, a drug that interacts with oestrogen receptors, was used as a carrier to deliver ferrocene to breast cancer cells. For this aim tamoxifen conjugated to ferrocene (Tam‐Fer) was synthesized. We have shown that the frequency of apoptotic events in MCF‐7 breast cancer cells treated with Tam‐Fer is significantly higher than in cells treated with tamoxifen or ferrocene separately. The increase of apoptosis correlates well with the rise in generation of reactive oxygen species in cancer cells. These results show that the hydrogen peroxide overproduced in tumour cells can serve as a prodrug for the treatment of cancer. |
| doi_str_mv | 10.1211/jpp.59.11.0013 |
| format | Article |
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Hydrogen peroxide serves as a prodrug in the presence of transition metal ions, such as iron delivered by ferrocene. Under the effect of ferrocene, hydrogen peroxide is split into hydroxyl anions and highly reactive hydroxyl radicals. The latter cause oxidative DNA damage, which induces apoptosis, leading to elimination of cancer cells. Tamoxifen, a drug that interacts with oestrogen receptors, was used as a carrier to deliver ferrocene to breast cancer cells. For this aim tamoxifen conjugated to ferrocene (Tam‐Fer) was synthesized. We have shown that the frequency of apoptotic events in MCF‐7 breast cancer cells treated with Tam‐Fer is significantly higher than in cells treated with tamoxifen or ferrocene separately. The increase of apoptosis correlates well with the rise in generation of reactive oxygen species in cancer cells. These results show that the hydrogen peroxide overproduced in tumour cells can serve as a prodrug for the treatment of cancer.</description><identifier>ISSN: 0022-3573</identifier><identifier>EISSN: 2042-7158</identifier><identifier>DOI: 10.1211/jpp.59.11.0013</identifier><identifier>PMID: 17976267</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Antineoplastic Agents, Hormonal - chemistry ; Antineoplastic Agents, Hormonal - pharmacology ; Apoptosis - drug effects ; Breast Neoplasms - drug therapy ; Breast Neoplasms - metabolism ; DNA Damage - drug effects ; Drug Delivery Systems ; Female ; Ferrous Compounds - chemistry ; Ferrous Compounds - pharmacology ; Humans ; Hydrogen Peroxide - metabolism ; Hydroxyl Radical - metabolism ; Metallocenes ; Prodrugs ; Reactive Oxygen Species - metabolism ; Receptors, Estrogen - metabolism ; Tamoxifen - chemistry ; Tamoxifen - pharmacology ; Tumor Cells, Cultured</subject><ispartof>Journal of pharmacy and pharmacology, 2007-11, Vol.59 (11), p.1549-1553</ispartof><rights>2007 Royal Pharmaceutical Society of Great Britain</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5132-29b9c975502428e32544e7bdb19a49b281df8187ec98d81993fbd0c84f355f8e3</citedby><cites>FETCH-LOGICAL-c5132-29b9c975502428e32544e7bdb19a49b281df8187ec98d81993fbd0c84f355f8e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1211%2Fjpp.59.11.0013$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1211%2Fjpp.59.11.0013$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17976267$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wlassoff, Wjatschesslaw A.</creatorcontrib><creatorcontrib>Albright, Craig D.</creatorcontrib><creatorcontrib>Sivashinski, Michael S.</creatorcontrib><creatorcontrib>Ivanova, Anastasia</creatorcontrib><creatorcontrib>Appelbaum, Jacob G.</creatorcontrib><creatorcontrib>Salganik, Rudolph I.</creatorcontrib><title>Hydrogen peroxide overproduced in breast cancer cells can serve as an anticancer prodrug generating apoptosis-stimulating hydroxyl radicals under the effect of tamoxifen-ferrocene conjugate</title><title>Journal of pharmacy and pharmacology</title><addtitle>J Pharm Pharmacol</addtitle><description>A new approach to the treatment of cancer is suggested, based on the innate overproduction of hydrogen peroxide in cancer cells. Hydrogen peroxide serves as a prodrug in the presence of transition metal ions, such as iron delivered by ferrocene. Under the effect of ferrocene, hydrogen peroxide is split into hydroxyl anions and highly reactive hydroxyl radicals. The latter cause oxidative DNA damage, which induces apoptosis, leading to elimination of cancer cells. Tamoxifen, a drug that interacts with oestrogen receptors, was used as a carrier to deliver ferrocene to breast cancer cells. For this aim tamoxifen conjugated to ferrocene (Tam‐Fer) was synthesized. We have shown that the frequency of apoptotic events in MCF‐7 breast cancer cells treated with Tam‐Fer is significantly higher than in cells treated with tamoxifen or ferrocene separately. The increase of apoptosis correlates well with the rise in generation of reactive oxygen species in cancer cells. These results show that the hydrogen peroxide overproduced in tumour cells can serve as a prodrug for the treatment of cancer.</description><subject>Antineoplastic Agents, Hormonal - chemistry</subject><subject>Antineoplastic Agents, Hormonal - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Breast Neoplasms - drug therapy</subject><subject>Breast Neoplasms - metabolism</subject><subject>DNA Damage - drug effects</subject><subject>Drug Delivery Systems</subject><subject>Female</subject><subject>Ferrous Compounds - chemistry</subject><subject>Ferrous Compounds - pharmacology</subject><subject>Humans</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>Hydroxyl Radical - metabolism</subject><subject>Metallocenes</subject><subject>Prodrugs</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Receptors, Estrogen - metabolism</subject><subject>Tamoxifen - chemistry</subject><subject>Tamoxifen - pharmacology</subject><subject>Tumor Cells, Cultured</subject><issn>0022-3573</issn><issn>2042-7158</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU1v0zAchyMEYmVw5Yh84pbglziOj2hAu2mCCQ12tBz77y6ljTPbGe2H47vhqBUcd_KLfs_jl19RvCW4IpSQD5txrLisCKkwJuxZsaC4pqUgvH1eLDCmtGRcsLPiVYwbjLFomuZlcUaEFA1txKL4szrY4NcwoBGC3_cWkH-EMAZvJwMW9QPqAuiYkNGDgYAMbLdxXqAI4RGQjijP9ZD6U2BGw7RG2QlBp35YIz36MfnYxzKmfjdtj7v388n7wxYFbTOcrdNgsyDdAwLnwCTkHUp6l6_lYCgdhOBNtiLjh8201gleFy9cBuHNaTwvfnz5fHuxKq-_LS8vPl6XhhNGSyo7aaTgHNOatsAor2sQne2I1LXsaEusa0krwMjWtkRK5jqLTVs7xrnLwHnx_ujNj3uYICa16-P8E3oAP0XVtHVDMGNPBinGTcukyMHqGDTBxxjAqTH0Ox0OimA1N6tys4pLlWdzsxl4dzJP3Q7s__ipyhyoj4Hf_RYOT-jU1c3qhjSSZqw8Yn1MsP-H6fBLZang6u7rUi3pkn-6vfupvrO_UkjEBw</recordid><startdate>200711</startdate><enddate>200711</enddate><creator>Wlassoff, Wjatschesslaw A.</creator><creator>Albright, Craig D.</creator><creator>Sivashinski, Michael S.</creator><creator>Ivanova, Anastasia</creator><creator>Appelbaum, Jacob G.</creator><creator>Salganik, Rudolph I.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>200711</creationdate><title>Hydrogen peroxide overproduced in breast cancer cells can serve as an anticancer prodrug generating apoptosis-stimulating hydroxyl radicals under the effect of tamoxifen-ferrocene conjugate</title><author>Wlassoff, Wjatschesslaw A. ; 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Hydrogen peroxide serves as a prodrug in the presence of transition metal ions, such as iron delivered by ferrocene. Under the effect of ferrocene, hydrogen peroxide is split into hydroxyl anions and highly reactive hydroxyl radicals. The latter cause oxidative DNA damage, which induces apoptosis, leading to elimination of cancer cells. Tamoxifen, a drug that interacts with oestrogen receptors, was used as a carrier to deliver ferrocene to breast cancer cells. For this aim tamoxifen conjugated to ferrocene (Tam‐Fer) was synthesized. We have shown that the frequency of apoptotic events in MCF‐7 breast cancer cells treated with Tam‐Fer is significantly higher than in cells treated with tamoxifen or ferrocene separately. The increase of apoptosis correlates well with the rise in generation of reactive oxygen species in cancer cells. 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| source | MEDLINE; Wiley Online Library Journals Frontfile Complete; Oxford University Press Journals All Titles (1996-Current) |
| subjects | Antineoplastic Agents, Hormonal - chemistry Antineoplastic Agents, Hormonal - pharmacology Apoptosis - drug effects Breast Neoplasms - drug therapy Breast Neoplasms - metabolism DNA Damage - drug effects Drug Delivery Systems Female Ferrous Compounds - chemistry Ferrous Compounds - pharmacology Humans Hydrogen Peroxide - metabolism Hydroxyl Radical - metabolism Metallocenes Prodrugs Reactive Oxygen Species - metabolism Receptors, Estrogen - metabolism Tamoxifen - chemistry Tamoxifen - pharmacology Tumor Cells, Cultured |
| title | Hydrogen peroxide overproduced in breast cancer cells can serve as an anticancer prodrug generating apoptosis-stimulating hydroxyl radicals under the effect of tamoxifen-ferrocene conjugate |
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