Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels.
There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pa...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2017-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC5481018?pdf=render |
| _version_ | 1811287610261241856 |
|---|---|
| author | Mustafa Nazıroğlu Bilal Çiğ Walter Blum Csaba Vizler Andrea Buhala Annamária Marton Róbert Katona Katalin Jósvay Beat Schwaller Zoltán Oláh László Pecze |
| author_facet | Mustafa Nazıroğlu Bilal Çiğ Walter Blum Csaba Vizler Andrea Buhala Annamária Marton Róbert Katona Katalin Jósvay Beat Schwaller Zoltán Oláh László Pecze |
| author_sort | Mustafa Nazıroğlu |
| collection | DOAJ |
| description | There is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells. This indicates that MCF7 cells not only express functional TRPV1 channels, but also produce endogenous TRPV1 agonists. We investigated the effects of MRS1477 and capsaicin on cell viability, caspase-3 and -9 activities and reactive oxygen species production in MCF7 cells. The fraction of apoptotic cells was increased after 3 days incubation with capsaicin (10 μM) paralleled by increased reactive oxygen species production and caspase activity. These effects were even more pronounced, when cells were incubated with MRS1477 (2 μM) either alone or together with CAPS (10 μM). Capsazepine, a TRPV1 blocker, inhibited both the effect of capsaicin and MRS1477. Whole-cell patch clamp recordings revealed that capsaicin-evoked TRPV1-mediated current density levels were increased after 3 days incubation with MRS1477 (2 μM). However, the tumor growth in MCF7 tumor-bearing immunodeficient mice was not significantly decreased after treatment with MRS1477 (10 mg/ kg body weight, i.p., injection twice a week). In conclusion, in view of a putative in vivo treatment with MRS1477 or similar compounds further optimization is required. |
| first_indexed | 2024-04-13T03:21:35Z |
| format | Article |
| id | doaj.art-1c756edbdabe4983a5672df4a6136ff1 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T03:21:35Z |
| publishDate | 2017-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1c756edbdabe4983a5672df4a6136ff12022-12-22T03:04:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017995010.1371/journal.pone.0179950Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels.Mustafa NazıroğluBilal ÇiğWalter BlumCsaba VizlerAndrea BuhalaAnnamária MartonRóbert KatonaKatalin JósvayBeat SchwallerZoltán OláhLászló PeczeThere is convincing epidemiological and experimental evidence that capsaicin, a potent natural transient receptor potential cation channel vanilloid member 1 (TRPV1) agonist, has anticancer activity. However, capsaicin cannot be given systemically in large doses, because of its induction of acute pain and neurological inflammation. MRS1477, a dihydropyridine derivative acts as a positive allosteric modulator of TRPV1, if added together with capsaicin, but is ineffective, if given alone. Addition of MRS1477 evoked Ca2+ signals in MCF7 breast cancer cells, but not in primary breast epithelial cells. This indicates that MCF7 cells not only express functional TRPV1 channels, but also produce endogenous TRPV1 agonists. We investigated the effects of MRS1477 and capsaicin on cell viability, caspase-3 and -9 activities and reactive oxygen species production in MCF7 cells. The fraction of apoptotic cells was increased after 3 days incubation with capsaicin (10 μM) paralleled by increased reactive oxygen species production and caspase activity. These effects were even more pronounced, when cells were incubated with MRS1477 (2 μM) either alone or together with CAPS (10 μM). Capsazepine, a TRPV1 blocker, inhibited both the effect of capsaicin and MRS1477. Whole-cell patch clamp recordings revealed that capsaicin-evoked TRPV1-mediated current density levels were increased after 3 days incubation with MRS1477 (2 μM). However, the tumor growth in MCF7 tumor-bearing immunodeficient mice was not significantly decreased after treatment with MRS1477 (10 mg/ kg body weight, i.p., injection twice a week). In conclusion, in view of a putative in vivo treatment with MRS1477 or similar compounds further optimization is required.http://europepmc.org/articles/PMC5481018?pdf=render |
| spellingShingle | Mustafa Nazıroğlu Bilal Çiğ Walter Blum Csaba Vizler Andrea Buhala Annamária Marton Róbert Katona Katalin Jósvay Beat Schwaller Zoltán Oláh László Pecze Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels. PLoS ONE |
| title | Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels. |
| title_full | Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels. |
| title_fullStr | Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels. |
| title_full_unstemmed | Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels. |
| title_short | Targeting breast cancer cells by MRS1477, a positive allosteric modulator of TRPV1 channels. |
| title_sort | targeting breast cancer cells by mrs1477 a positive allosteric modulator of trpv1 channels |
| url | http://europepmc.org/articles/PMC5481018?pdf=render |
| work_keys_str_mv | AT mustafanazıroglu targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT bilalcig targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT walterblum targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT csabavizler targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT andreabuhala targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT annamariamarton targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT robertkatona targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT katalinjosvay targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT beatschwaller targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT zoltanolah targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels AT laszlopecze targetingbreastcancercellsbymrs1477apositiveallostericmodulatoroftrpv1channels |