A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins
Abstract
:1. Introduction
Chalcone | Plant Source | Type of Cancer | Reference |
---|---|---|---|
Helichrysetin | Alpinia (Zingiberaceae) and Helichrysum (Asteraceae) | Cervical, gastric, glioblastoma, and lung | [21,22,23,24,25] |
Xanthohumol | Humulus lupulus (Cannabaceae) | Melanoma, gastric, breast, prostate, lung, pancreatic, ovarian, neuroblastoma, prostate, and colon | [26,27,28,29,30,31,32,33]. |
Cardamonin | Zingiberaceae family, Artemisia and Helichrysum (Asteraceae), Carya (Ju-glandaceae), Vitex (Verbenaceae), Desmos(Annonaceae), Comptonia and Morella (Myricaceae), Combretum (Com-bretaceae), Syzygium (Myrtaceae), Piper (Piperaceae), Polygonum (Polygona-ceae), Populus (Salicaceae), Cedrelopsis (Rutaceae), and Woodsia (Dryopteridaceae) | Breast, gastric, colon, and ovarian | [34,35,36,37,38,39,40,41,42] |
Flavokawain A | Piper methysticum (Piperaceae) and Goniothalamus gardneri (Annonaceae) | Breast, lung, and prostate | [1,43,44,45,46] |
Flavokawain B | Piper methysticum (Piperaceae), Alpinia pricei Hayata, and Alpinia pricei rhizome (Zingiberaceae) | Breast, colon, lung, and prostate | [1,47,48,49,50,51,52,53,54] |
Flavokawain C | Didymocarpus corchorijolia (Gesneriaceae) and Aniba riparia (Lauraceae) | Breast, colon, and ovarian | [1,55,56,57,58,59] |
Licochalcone A | Glycyrrhiza glabra and Glycyrrhiza inflata (Fabaceae) | Colon, breast, lung, and bladder | [60,61,62,63,64,65,66,67,68,69,70,71] |
Broussochalcone A | Broussonetia papyrifera (Moraceae) | Renal | [72] |
Isobavachalcone | Psoralea corylifolia (Leguminosae) | Breast | [73,74] |
Pinostrobin | Uvaria chamae (Annonaceae) | Breast and prostate | [75,76] |
2. Results
2.1. Structural Analysis
2.2. Anti-Cancer Potential of Chalcotanina
2.2.1. Selective Cytotoxicity of Chalcotanina on Cancer Cells
2.2.2. Profiles of Annexin-V/7-AAD and Casp3/7 Activation in Chalcotanina-Induced Apoptosis in Cancer Cells
2.2.3. Chalcotanina Induces Intrinsic Apoptosis via Depolarization of Mitochondrial Membrane Potential in TNBC Cells
2.2.4. Chalcotanina Targeting Autophagy in Cancer Cells
2.3. Docking and Molecular Dynamics Demonstrate the Negative Modulation of Pro-Survival Proteins
3. Discussion
4. Materials and Methods
4.1. Chalcone Extraction and Isolation
4.2. Structural Identification
4.3. Cell Lines, Culture, and Analysis
4.4. Cell Viability Assay and Selectivity of Chalcones
4.5. Detection of Apoptosis Induction in Response to Chalcotanina
4.5.1. Flow Cytometry
4.5.2. Western Blot
4.5.3. Morphological Analysis of Nuclei and Microtubules with Epifluorescent Microscopy
4.6. Analysis of Intrinsic Pathway of Apoptosis in TNBC cells
4.6.1. Changes in the Mitochondrial Membrane Potential (ΔΨm)
4.6.2. Pro- and Anti-Apoptotic Proteins Analysis by Western Blot
4.6.3. Phospho-Bcl-2 Protein Detection
4.7. Autophagy Induction in TNBC Cells Exposed to Chalcotanina
4.8. Statistical Analysis for Biological Test
4.9. Molecular Docking and Molecular Dynamics
4.9.1. Molecular Dynamics Simulation Preparations
4.9.2. Molecular Dynamics Configuration
4.9.3. MMPBSA
4.9.4. RMSD, RMSF, and Rg
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Position | Chalcone | |
---|---|---|
δH (J in Hz) | δC (ppm) | |
C-1 | - | 127.73 |
C-2 | 7.27 (1H, d, J = 2.1 Hz) | 114.44 |
C-3 | - | 145.48 |
C-4 | - | 148.11 |
C-5 | 6.91(1H, d, J = 8.2 Hz) | 115.61 |
C-6 | 7.14 (1H, dd, J = 8.3, 1.9 Hz) | 122.33 |
C-α | 7.71 (1H, d, J = 15.5 Hz) | 124.20 |
C-β | 7.86 (1H, d, J = 15.5 Hz) | 142.21 |
C-β′ | - | 192.42 |
C-1′ | - | 105.92 |
C-2′ | - | 166.36 |
C-3′ | 6.10 (1H, d, J = 2.4 Hz) | 93.78 |
C-4′ | - | 168.26 |
C-4′-OCH3 | 3.89 (3H, s) | 55.17 |
C-5′ | 6.13 (1H, d, J = 2.4 Hz) | 90.90 |
C-6′ | - | 162.77 |
C-6′-OCH3 | 4.02 (3H, s) | 55.62 |
Reactive | Chalcone | ||
---|---|---|---|
Band II (nm) | Band I (nm) | Displacement (nm) | |
MeOH | 276 | 387 | - |
MeOH + MeONa | 276 | 479 | B I:72 |
MeOH + AcONa | 276 | 417 | B I: 30 |
MeOH + AcONa + H3BO3 | 276 | 415 | B I:28 |
MeOH + AlCl3 | 276 | 401 | B I:14 |
MeOH + AlCl3 + HCl | 276 | 387 | NCh. |
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Mendez-Callejas, G.; Piñeros-Avila, M.; Yosa-Reyes, J.; Pestana-Nobles, R.; Torrenegra, R.; Camargo-Ubate, M.F.; Bello-Castro, A.E.; Celis, C.A. A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins. Int. J. Mol. Sci. 2023, 24, 15185. https://doi.org/10.3390/ijms242015185
Mendez-Callejas G, Piñeros-Avila M, Yosa-Reyes J, Pestana-Nobles R, Torrenegra R, Camargo-Ubate MF, Bello-Castro AE, Celis CA. A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins. International Journal of Molecular Sciences. 2023; 24(20):15185. https://doi.org/10.3390/ijms242015185
Chicago/Turabian StyleMendez-Callejas, Gina, Marco Piñeros-Avila, Juvenal Yosa-Reyes, Roberto Pestana-Nobles, Ruben Torrenegra, María F. Camargo-Ubate, Andrea E. Bello-Castro, and Crispin A. Celis. 2023. "A Novel Tri-Hydroxy-Methylated Chalcone Isolated from Chromolaena tacotana with Anti-Cancer Potential Targeting Pro-Survival Proteins" International Journal of Molecular Sciences 24, no. 20: 15185. https://doi.org/10.3390/ijms242015185