In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives
Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by m...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/1/168 |
| _version_ | 1797499314309693440 |
|---|---|
| author | Ibrahim Morgan Ludger A. Wessjohann Goran N. Kaluđerović |
| author_facet | Ibrahim Morgan Ludger A. Wessjohann Goran N. Kaluđerović |
| author_sort | Ibrahim Morgan |
| collection | DOAJ |
| description | Anthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. In this study, various nature inspired synthetic anthraquinone derivatives were tested against colon, prostate, liver and cervical cancer cell lines. Most of the compounds exhibit anticancer effects against all cell lines, therefore the compounds were further studied to determine their IC<sub>50</sub>-values. Of these compounds, 1,4-bis(benzyloxy)-2,3-bis(hydroxymethyl)anthracene-9,10-dione (<b>4</b>) exhibited the highest cytotoxicity against PC3 cells and was chosen for a deeper look into its mechanism of action. Based on flow cytometry, the compound was proven to induce apoptosis through the activation of caspases and to demolish the ROS/RNS and NO equilibrium in the PC3 cell line. It trapped cells in the G2/M phase. Western blotting was performed for several proteins related to the effects observed. Compound <b>4</b> enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase. |
| first_indexed | 2024-03-10T03:45:39Z |
| format | Article |
| id | doaj.art-ac852158926b4ea6809c7e7f295c5ebf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:45:39Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-ac852158926b4ea6809c7e7f295c5ebf2023-11-23T11:21:12ZengMDPI AGCells2073-44092022-01-0111116810.3390/cells11010168In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone DerivativesIbrahim Morgan0Ludger A. Wessjohann1Goran N. Kaluđerović2Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), GermanyDepartment of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), GermanyDepartment of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, 06120 Halle (Saale), GermanyAnthraquinone derivatives exhibit various biological activities, e.g., antifungal, antibacterial and in vitro antiviral activities. They are naturally produced in many fungal and plant families such as Rhamnaceae or Fabaceae. Furthermore, they were found to have anticancer activity, exemplified by mitoxantrone and pixantrone, and many are well known redox-active compounds. In this study, various nature inspired synthetic anthraquinone derivatives were tested against colon, prostate, liver and cervical cancer cell lines. Most of the compounds exhibit anticancer effects against all cell lines, therefore the compounds were further studied to determine their IC<sub>50</sub>-values. Of these compounds, 1,4-bis(benzyloxy)-2,3-bis(hydroxymethyl)anthracene-9,10-dione (<b>4</b>) exhibited the highest cytotoxicity against PC3 cells and was chosen for a deeper look into its mechanism of action. Based on flow cytometry, the compound was proven to induce apoptosis through the activation of caspases and to demolish the ROS/RNS and NO equilibrium in the PC3 cell line. It trapped cells in the G2/M phase. Western blotting was performed for several proteins related to the effects observed. Compound <b>4</b> enhanced the production of PARP and caspase-3. Moreover, it activated the conversion of LC3A/B-I to LC3A/B-II showing that also autophagy plays a role in its mechanism of action, and it caused the phosphorylation of p70 s6 kinase.https://www.mdpi.com/2073-4409/11/1/168anthraquinonecytotoxicityapoptosiscell cyclecaspaseautophagy |
| spellingShingle | Ibrahim Morgan Ludger A. Wessjohann Goran N. Kaluđerović In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives Cells anthraquinone cytotoxicity apoptosis cell cycle caspase autophagy |
| title | In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives |
| title_full | In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives |
| title_fullStr | In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives |
| title_full_unstemmed | In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives |
| title_short | In Vitro Anticancer Screening and Preliminary Mechanistic Study of A-Ring Substituted Anthraquinone Derivatives |
| title_sort | in vitro anticancer screening and preliminary mechanistic study of a ring substituted anthraquinone derivatives |
| topic | anthraquinone cytotoxicity apoptosis cell cycle caspase autophagy |
| url | https://www.mdpi.com/2073-4409/11/1/168 |
| work_keys_str_mv | AT ibrahimmorgan invitroanticancerscreeningandpreliminarymechanisticstudyofaringsubstitutedanthraquinonederivatives AT ludgerawessjohann invitroanticancerscreeningandpreliminarymechanisticstudyofaringsubstitutedanthraquinonederivatives AT gorannkaluđerovic invitroanticancerscreeningandpreliminarymechanisticstudyofaringsubstitutedanthraquinonederivatives |