The Parotoid Gland Secretion from Peruvian Toad <i>Rhinella horribilis</i> (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells
Since <i>Rhinella</i> sp. toads produce bioactive substances, some species have been used in traditional medicine and magical practices by ancient cultures in Peru. During several decades, the <i>Rhinella horribilis</i> toad was confused with the invasive toad <i>Rhinel...
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MDPI AG
2020-09-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/12/9/608 |
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| author | Guillermo Schmeda-Hirschmann Jean Paulo de Andrade Marilú Roxana Soto-Vasquez Paul Alan Arkin Alvarado-García Charlotte Palominos Sebastián Fuentes-Retamal Mathias Mellado Pablo Correa Félix A. Urra |
| author_facet | Guillermo Schmeda-Hirschmann Jean Paulo de Andrade Marilú Roxana Soto-Vasquez Paul Alan Arkin Alvarado-García Charlotte Palominos Sebastián Fuentes-Retamal Mathias Mellado Pablo Correa Félix A. Urra |
| author_sort | Guillermo Schmeda-Hirschmann |
| collection | DOAJ |
| description | Since <i>Rhinella</i> sp. toads produce bioactive substances, some species have been used in traditional medicine and magical practices by ancient cultures in Peru. During several decades, the <i>Rhinella horribilis</i> toad was confused with the invasive toad <i>Rhinella marina</i>, a species documented with extensive toxinological studies. In contrast, the chemical composition and biological effects of the parotoid gland secretions (PGS) remain still unknown for <i>R. horribilis</i>. In this work, we determine for the first time 55 compounds from the PGS of <i>R. horribilis</i>, which were identified using HPLC-MS/MS. The crude extract inhibited the proliferation of A549 cancer cells with IC<sub>50</sub> values of 0.031 ± 0.007 and 0.015 ± 0.001 µg/mL at 24 and 48 h of exposure, respectively. Moreover, it inhibited the clonogenic capacity, increased ROS levels, and prevented the etoposide-induced apoptosis, suggesting that the effect of <i>R. horribilis</i> poison secretion was by cell cycle blocking before of G2/M-phase checkpoint. Fraction B was the most active and strongly inhibited cancer cell migration. Our results indicate that the PGS of <i>R. horribilis</i> are composed of alkaloids, bufadienolides, and argininyl diacids derivatives, inhibiting the proliferation and migration of A549 cells. |
| first_indexed | 2024-03-10T16:08:59Z |
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| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T16:08:59Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-adb2816951b744b6a9709e0cc190b2d02023-11-20T14:40:11ZengMDPI AGToxins2072-66512020-09-0112960810.3390/toxins12090608The Parotoid Gland Secretion from Peruvian Toad <i>Rhinella horribilis</i> (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer CellsGuillermo Schmeda-Hirschmann0Jean Paulo de Andrade1Marilú Roxana Soto-Vasquez2Paul Alan Arkin Alvarado-García3Charlotte Palominos4Sebastián Fuentes-Retamal5Mathias Mellado6Pablo Correa7Félix A. Urra8Laboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Campus Lircay, Talca 3460000, ChileLaboratorio de Química de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad de Talca, Campus Lircay, Talca 3460000, ChileLaboratorio de Farmacognosia, Facultad de Farmacia y Bioquímica, Universidad Nacional de Trujillo, Trujillo 13011, PeruFacultad de Medicina, Universidad Privada Antenor Orrego, Trujillo 13001, PeruLaboratorio de Plasticidad Metabólica y Bioenergética, Programa de Farmacología Clínica y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileLaboratorio de Plasticidad Metabólica y Bioenergética, Programa de Farmacología Clínica y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileLaboratorio de Plasticidad Metabólica y Bioenergética, Programa de Farmacología Clínica y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileLaboratorio de Plasticidad Metabólica y Bioenergética, Programa de Farmacología Clínica y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileLaboratorio de Plasticidad Metabólica y Bioenergética, Programa de Farmacología Clínica y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago 8380453, ChileSince <i>Rhinella</i> sp. toads produce bioactive substances, some species have been used in traditional medicine and magical practices by ancient cultures in Peru. During several decades, the <i>Rhinella horribilis</i> toad was confused with the invasive toad <i>Rhinella marina</i>, a species documented with extensive toxinological studies. In contrast, the chemical composition and biological effects of the parotoid gland secretions (PGS) remain still unknown for <i>R. horribilis</i>. In this work, we determine for the first time 55 compounds from the PGS of <i>R. horribilis</i>, which were identified using HPLC-MS/MS. The crude extract inhibited the proliferation of A549 cancer cells with IC<sub>50</sub> values of 0.031 ± 0.007 and 0.015 ± 0.001 µg/mL at 24 and 48 h of exposure, respectively. Moreover, it inhibited the clonogenic capacity, increased ROS levels, and prevented the etoposide-induced apoptosis, suggesting that the effect of <i>R. horribilis</i> poison secretion was by cell cycle blocking before of G2/M-phase checkpoint. Fraction B was the most active and strongly inhibited cancer cell migration. Our results indicate that the PGS of <i>R. horribilis</i> are composed of alkaloids, bufadienolides, and argininyl diacids derivatives, inhibiting the proliferation and migration of A549 cells.https://www.mdpi.com/2072-6651/12/9/608<i>Rhinella horribilis</i>toad toxinsPerucell migrationproliferationetoposide |
| spellingShingle | Guillermo Schmeda-Hirschmann Jean Paulo de Andrade Marilú Roxana Soto-Vasquez Paul Alan Arkin Alvarado-García Charlotte Palominos Sebastián Fuentes-Retamal Mathias Mellado Pablo Correa Félix A. Urra The Parotoid Gland Secretion from Peruvian Toad <i>Rhinella horribilis</i> (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells Toxins <i>Rhinella horribilis</i> toad toxins Peru cell migration proliferation etoposide |
| title | The Parotoid Gland Secretion from Peruvian Toad <i>Rhinella horribilis</i> (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells |
| title_full | The Parotoid Gland Secretion from Peruvian Toad <i>Rhinella horribilis</i> (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells |
| title_fullStr | The Parotoid Gland Secretion from Peruvian Toad <i>Rhinella horribilis</i> (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells |
| title_full_unstemmed | The Parotoid Gland Secretion from Peruvian Toad <i>Rhinella horribilis</i> (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells |
| title_short | The Parotoid Gland Secretion from Peruvian Toad <i>Rhinella horribilis</i> (Wiegmann, 1833): Chemical Composition and Effect on the Proliferation and Migration of Lung Cancer Cells |
| title_sort | parotoid gland secretion from peruvian toad i rhinella horribilis i wiegmann 1833 chemical composition and effect on the proliferation and migration of lung cancer cells |
| topic | <i>Rhinella horribilis</i> toad toxins Peru cell migration proliferation etoposide |
| url | https://www.mdpi.com/2072-6651/12/9/608 |
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