Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis
Glioblastoma is the most aggressive and lethal brain tumor in adults, presenting diffuse brain infiltration, necrosis, and drug resistance. Although new drugs have been approved for recurrent patients, the median survival rate is two years; therefore, new alternatives to treat these patients are req...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-05-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/13/6/869 |
| _version_ | 1827738208209731584 |
|---|---|
| author | Miguel Hernández-Cerón Víctor Chavarria Camilo Ríos Benjamin Pineda Francisca Palomares-Alonso Irma Susana Rojas-Tomé Helgi Jung-Cook |
| author_facet | Miguel Hernández-Cerón Víctor Chavarria Camilo Ríos Benjamin Pineda Francisca Palomares-Alonso Irma Susana Rojas-Tomé Helgi Jung-Cook |
| author_sort | Miguel Hernández-Cerón |
| collection | DOAJ |
| description | Glioblastoma is the most aggressive and lethal brain tumor in adults, presenting diffuse brain infiltration, necrosis, and drug resistance. Although new drugs have been approved for recurrent patients, the median survival rate is two years; therefore, new alternatives to treat these patients are required. Previous studies have reported the anticancer activity of albendazole, its active metabolite albendazole sulfoxide, and melatonin; therefore, the present study was performed to evaluate if the combination of melatonin with albendazole or with albendazole sulfoxide induces an additive or synergistic cytotoxic effect on C6 and RG2 rat glioma cells, as well as on U87 human glioblastoma cells. Drug interaction was determined by the Chou–Talalay method. We evaluated the mechanism of cell death by flow cytometry, immunofluorescence, and crystal violet staining. The cytotoxicity of the combinations was mainly synergistic. The combined treatments induced significantly more apoptotic and autophagic cell death on the glioma cell lines. Additionally, albendazole and albendazole sulfoxide inhibited proliferation independently of melatonin. Our data justify continuing with the evaluation of this proposal since the combinations could be a potential strategy to aid in the treatment of glioblastoma. |
| first_indexed | 2024-03-11T02:41:13Z |
| format | Article |
| id | doaj.art-ed8c54b4f0c24fb78c195d98f76af8ed |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-11T02:41:13Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-ed8c54b4f0c24fb78c195d98f76af8ed2023-11-18T09:35:41ZengMDPI AGBrain Sciences2076-34252023-05-0113686910.3390/brainsci13060869Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and ApoptosisMiguel Hernández-Cerón0Víctor Chavarria1Camilo Ríos2Benjamin Pineda3Francisca Palomares-Alonso4Irma Susana Rojas-Tomé5Helgi Jung-Cook6Doctorate in Biological and Health Sciences, Universidad Autónoma Metropolitana, Mexico City 04960, MexicoNeuroimmunology and Neuro-Oncology Unit, Instituto Nacional de Neurología y Neurocirugía (INNN), Mexico City 14269, MexicoDoctorate in Biological and Health Sciences, Universidad Autónoma Metropolitana, Mexico City 04960, MexicoNeuroimmunology and Neuro-Oncology Unit, Instituto Nacional de Neurología y Neurocirugía (INNN), Mexico City 14269, MexicoNeuropsycopharmacology Lab, Instituto Nacional de Neurología y Neurocirugía, Mexico City 14269, MexicoNeuropsycopharmacology Lab, Instituto Nacional de Neurología y Neurocirugía, Mexico City 14269, MexicoPharmacy Department, Universidad Nacional Autónoma de México, Mexico City 04510, MexicoGlioblastoma is the most aggressive and lethal brain tumor in adults, presenting diffuse brain infiltration, necrosis, and drug resistance. Although new drugs have been approved for recurrent patients, the median survival rate is two years; therefore, new alternatives to treat these patients are required. Previous studies have reported the anticancer activity of albendazole, its active metabolite albendazole sulfoxide, and melatonin; therefore, the present study was performed to evaluate if the combination of melatonin with albendazole or with albendazole sulfoxide induces an additive or synergistic cytotoxic effect on C6 and RG2 rat glioma cells, as well as on U87 human glioblastoma cells. Drug interaction was determined by the Chou–Talalay method. We evaluated the mechanism of cell death by flow cytometry, immunofluorescence, and crystal violet staining. The cytotoxicity of the combinations was mainly synergistic. The combined treatments induced significantly more apoptotic and autophagic cell death on the glioma cell lines. Additionally, albendazole and albendazole sulfoxide inhibited proliferation independently of melatonin. Our data justify continuing with the evaluation of this proposal since the combinations could be a potential strategy to aid in the treatment of glioblastoma.https://www.mdpi.com/2076-3425/13/6/869glioblastomamelatoninalbendazolealbendazole sulfoxidesynergism |
| spellingShingle | Miguel Hernández-Cerón Víctor Chavarria Camilo Ríos Benjamin Pineda Francisca Palomares-Alonso Irma Susana Rojas-Tomé Helgi Jung-Cook Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis Brain Sciences glioblastoma melatonin albendazole albendazole sulfoxide synergism |
| title | Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis |
| title_full | Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis |
| title_fullStr | Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis |
| title_full_unstemmed | Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis |
| title_short | Melatonin in Combination with Albendazole or Albendazole Sulfoxide Produces a Synergistic Cytotoxicity against Malignant Glioma Cells through Autophagy and Apoptosis |
| title_sort | melatonin in combination with albendazole or albendazole sulfoxide produces a synergistic cytotoxicity against malignant glioma cells through autophagy and apoptosis |
| topic | glioblastoma melatonin albendazole albendazole sulfoxide synergism |
| url | https://www.mdpi.com/2076-3425/13/6/869 |
| work_keys_str_mv | AT miguelhernandezceron melatoninincombinationwithalbendazoleoralbendazolesulfoxideproducesasynergisticcytotoxicityagainstmalignantgliomacellsthroughautophagyandapoptosis AT victorchavarria melatoninincombinationwithalbendazoleoralbendazolesulfoxideproducesasynergisticcytotoxicityagainstmalignantgliomacellsthroughautophagyandapoptosis AT camilorios melatoninincombinationwithalbendazoleoralbendazolesulfoxideproducesasynergisticcytotoxicityagainstmalignantgliomacellsthroughautophagyandapoptosis AT benjaminpineda melatoninincombinationwithalbendazoleoralbendazolesulfoxideproducesasynergisticcytotoxicityagainstmalignantgliomacellsthroughautophagyandapoptosis AT franciscapalomaresalonso melatoninincombinationwithalbendazoleoralbendazolesulfoxideproducesasynergisticcytotoxicityagainstmalignantgliomacellsthroughautophagyandapoptosis AT irmasusanarojastome melatoninincombinationwithalbendazoleoralbendazolesulfoxideproducesasynergisticcytotoxicityagainstmalignantgliomacellsthroughautophagyandapoptosis AT helgijungcook melatoninincombinationwithalbendazoleoralbendazolesulfoxideproducesasynergisticcytotoxicityagainstmalignantgliomacellsthroughautophagyandapoptosis |