Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines
Breast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. In this...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/15/12406 |
| _version_ | 1797586609354309632 |
|---|---|
| author | Angel Giovanni Arietta-García Fernando Calzada Israel Ramírez-Sánchez Elihú Bautista Normand García-Hernandez Rosa María Ordoñez-Razo |
| author_facet | Angel Giovanni Arietta-García Fernando Calzada Israel Ramírez-Sánchez Elihú Bautista Normand García-Hernandez Rosa María Ordoñez-Razo |
| author_sort | Angel Giovanni Arietta-García |
| collection | DOAJ |
| description | Breast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. In this study, through <i>in vitro</i> assays, it was observed that IA has similar cytotoxic activity between the subtypes triple negative, HER2+, and luminal A of the breast cancer cell lines. IA cytotoxic activity is higher in cancer than in nontumorigenic cells, and its selectivity index for cancer cells is more than that of the drug doxorubicin. Molecular docking and its <i>in silico</i> comparison with the 2-Deoxyglucose inhibitor suggest that IA could bind to Hexokinase II (HKII), decreasing its expression. Since we did not find changes in the expression of the glycolytic pathway, we suppose that IA could affect the antiapoptotic function of HKII in cancer cells. The IA-HKII union would activate the voltage-gated anion channel 1 (VDAC1), resuming apoptosis. Therefore, we suggest that IA could be used against almost any subtype and that its cytotoxic effect could be due to the reactivation of apoptosis in breast cancer cells. |
| first_indexed | 2024-03-11T00:25:32Z |
| format | Article |
| id | doaj.art-7c17a75a753543d294e032d2ebbc55f8 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T00:25:32Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-7c17a75a753543d294e032d2ebbc55f82023-11-18T23:04:36ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124151240610.3390/ijms241512406Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell LinesAngel Giovanni Arietta-García0Fernando Calzada1Israel Ramírez-Sánchez2Elihú Bautista3Normand García-Hernandez4Rosa María Ordoñez-Razo5Unidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría 2° Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, MexicoUnidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, 2° Piso CORSE, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, MexicoSección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City CP 07738, MexicoCONAHCYT—Consorcio de Investigación, Innovación y Desarrollo para las Zonas Áridas, Instituto Potosino de Investigación Científica y Tecnológica A.C., San Luis Potosí CP 78216, MexicoUnidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría 2° Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, MexicoUnidad de Investigación Médica en Genética Humana, UMAE Hospital de Pediatría 2° Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City CP 06725, MexicoBreast cancer treatments are limited by the cancer subtype and its selectivity towards tumor cells, hence the importance of finding compounds that increase the survival of healthy cells and target any subtype. Incomptine A (IA) is a sesquiterpene lactone with demonstrated cytotoxic activity. In this study, through <i>in vitro</i> assays, it was observed that IA has similar cytotoxic activity between the subtypes triple negative, HER2+, and luminal A of the breast cancer cell lines. IA cytotoxic activity is higher in cancer than in nontumorigenic cells, and its selectivity index for cancer cells is more than that of the drug doxorubicin. Molecular docking and its <i>in silico</i> comparison with the 2-Deoxyglucose inhibitor suggest that IA could bind to Hexokinase II (HKII), decreasing its expression. Since we did not find changes in the expression of the glycolytic pathway, we suppose that IA could affect the antiapoptotic function of HKII in cancer cells. The IA-HKII union would activate the voltage-gated anion channel 1 (VDAC1), resuming apoptosis. Therefore, we suggest that IA could be used against almost any subtype and that its cytotoxic effect could be due to the reactivation of apoptosis in breast cancer cells.https://www.mdpi.com/1422-0067/24/15/12406incomptine Abreast cancer cellscytotoxic activityHexokinase II |
| spellingShingle | Angel Giovanni Arietta-García Fernando Calzada Israel Ramírez-Sánchez Elihú Bautista Normand García-Hernandez Rosa María Ordoñez-Razo Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines International Journal of Molecular Sciences incomptine A breast cancer cells cytotoxic activity Hexokinase II |
| title | Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines |
| title_full | Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines |
| title_fullStr | Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines |
| title_full_unstemmed | Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines |
| title_short | Advances in the Properties of Incomptine A: Cytotoxic Activity and Downregulation of Hexokinase II in Breast Cancer Cell Lines |
| title_sort | advances in the properties of incomptine a cytotoxic activity and downregulation of hexokinase ii in breast cancer cell lines |
| topic | incomptine A breast cancer cells cytotoxic activity Hexokinase II |
| url | https://www.mdpi.com/1422-0067/24/15/12406 |
| work_keys_str_mv | AT angelgiovanniariettagarcia advancesinthepropertiesofincomptineacytotoxicactivityanddownregulationofhexokinaseiiinbreastcancercelllines AT fernandocalzada advancesinthepropertiesofincomptineacytotoxicactivityanddownregulationofhexokinaseiiinbreastcancercelllines AT israelramirezsanchez advancesinthepropertiesofincomptineacytotoxicactivityanddownregulationofhexokinaseiiinbreastcancercelllines AT elihubautista advancesinthepropertiesofincomptineacytotoxicactivityanddownregulationofhexokinaseiiinbreastcancercelllines AT normandgarciahernandez advancesinthepropertiesofincomptineacytotoxicactivityanddownregulationofhexokinaseiiinbreastcancercelllines AT rosamariaordonezrazo advancesinthepropertiesofincomptineacytotoxicactivityanddownregulationofhexokinaseiiinbreastcancercelllines |