Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells
<p>Abstract</p> <p>Background</p> <p>Curcumin induces apoptosis in many cancer cells and it reduces xenograft growth and the formation of lung metastases in nude mice. Moreover, the plant derived polyphenol has been reported to be able to overcome drug resistance to cla...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2009-12-01
|
| Series: | Molecular Cancer |
| Online Access: | http://www.molecular-cancer.com/content/8/1/129 |
| _version_ | 1818358872205688832 |
|---|---|
| author | Angelini Giovanna Mirisola Valentina Kronski Emanuel Killian Peter H Iancu Cristina M Bachmeier Beatrice E Jochum Marianne Nerlich Andreas G Pfeffer Ulrich |
| author_facet | Angelini Giovanna Mirisola Valentina Kronski Emanuel Killian Peter H Iancu Cristina M Bachmeier Beatrice E Jochum Marianne Nerlich Andreas G Pfeffer Ulrich |
| author_sort | Angelini Giovanna |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Curcumin induces apoptosis in many cancer cells and it reduces xenograft growth and the formation of lung metastases in nude mice. Moreover, the plant derived polyphenol has been reported to be able to overcome drug resistance to classical chemotherapy. These features render the drug a promising candidate for tumor therapy especially for cancers known for their high rates concerning therapy resistance like melanoma.</p> <p>Results</p> <p>We show here that the melanoma cell line M14 is resistant to Curcumin induced apoptosis, which correlates with the absence of any effect on NFκB signaling. We show that CXCL1 a chemokine that is down regulated in breast cancer cells by Curcumin in an NFκB dependant manner is expressed at variable levels in human melanomas. Yet in M14 cells, CXCL1 expression did not change upon Curcumin treatment. Following the hypothesis that Curcumin is rapidly removed from the resistant cells, we analyzed expression of known multi drug resistance genes and cellular transporters in M14 melanoma cells and in the Curcumin sensitive breast cancer cell line MDA-MB-231. ATP-binding cassette transporter ABCA1, a gene involved in the cellular lipid removal pathway is over-expressed in resistant M14 melanoma as compared to the sensitive MDA-MB-231 breast cancer cells. Gene silencing of ABCA1 by siRNA sensitizes M14 cells to the apoptotic effect of Curcumin most likely as a result of reduced basal levels of active NFκB. Moreover, ABCA1 silencing alone also induces apoptosis and reduces p65 expression.</p> <p>Conclusion</p> <p>Resistance to Curcumin thus follows classical pathways and ABCA1 expression should be considered as response marker.</p> |
| first_indexed | 2024-12-13T20:35:54Z |
| format | Article |
| id | doaj.art-38aebc9da4194dd9a663afd77b61bc8d |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-13T20:35:54Z |
| publishDate | 2009-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-38aebc9da4194dd9a663afd77b61bc8d2022-12-21T23:32:18ZengBMCMolecular Cancer1476-45982009-12-018112910.1186/1476-4598-8-129Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cellsAngelini GiovannaMirisola ValentinaKronski EmanuelKillian Peter HIancu Cristina MBachmeier Beatrice EJochum MarianneNerlich Andreas GPfeffer Ulrich<p>Abstract</p> <p>Background</p> <p>Curcumin induces apoptosis in many cancer cells and it reduces xenograft growth and the formation of lung metastases in nude mice. Moreover, the plant derived polyphenol has been reported to be able to overcome drug resistance to classical chemotherapy. These features render the drug a promising candidate for tumor therapy especially for cancers known for their high rates concerning therapy resistance like melanoma.</p> <p>Results</p> <p>We show here that the melanoma cell line M14 is resistant to Curcumin induced apoptosis, which correlates with the absence of any effect on NFκB signaling. We show that CXCL1 a chemokine that is down regulated in breast cancer cells by Curcumin in an NFκB dependant manner is expressed at variable levels in human melanomas. Yet in M14 cells, CXCL1 expression did not change upon Curcumin treatment. Following the hypothesis that Curcumin is rapidly removed from the resistant cells, we analyzed expression of known multi drug resistance genes and cellular transporters in M14 melanoma cells and in the Curcumin sensitive breast cancer cell line MDA-MB-231. ATP-binding cassette transporter ABCA1, a gene involved in the cellular lipid removal pathway is over-expressed in resistant M14 melanoma as compared to the sensitive MDA-MB-231 breast cancer cells. Gene silencing of ABCA1 by siRNA sensitizes M14 cells to the apoptotic effect of Curcumin most likely as a result of reduced basal levels of active NFκB. Moreover, ABCA1 silencing alone also induces apoptosis and reduces p65 expression.</p> <p>Conclusion</p> <p>Resistance to Curcumin thus follows classical pathways and ABCA1 expression should be considered as response marker.</p>http://www.molecular-cancer.com/content/8/1/129 |
| spellingShingle | Angelini Giovanna Mirisola Valentina Kronski Emanuel Killian Peter H Iancu Cristina M Bachmeier Beatrice E Jochum Marianne Nerlich Andreas G Pfeffer Ulrich Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells Molecular Cancer |
| title | Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells |
| title_full | Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells |
| title_fullStr | Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells |
| title_full_unstemmed | Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells |
| title_short | Overexpression of the ATP binding cassette gene ABCA1 determines resistance to Curcumin in M14 melanoma cells |
| title_sort | overexpression of the atp binding cassette gene abca1 determines resistance to curcumin in m14 melanoma cells |
| url | http://www.molecular-cancer.com/content/8/1/129 |
| work_keys_str_mv | AT angelinigiovanna overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells AT mirisolavalentina overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells AT kronskiemanuel overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells AT killianpeterh overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells AT iancucristinam overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells AT bachmeierbeatricee overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells AT jochummarianne overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells AT nerlichandreasg overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells AT pfefferulrich overexpressionoftheatpbindingcassettegeneabca1determinesresistancetocurcumininm14melanomacells |