Anticancer Activity of Benzo[a]phenoxazine Compounds Promoting Lysosomal Dysfunction
Abstract
:1. Introduction
2. Materials and Methods
2.1. Compounds, Cell Lines, and Culture Conditions
2.2. Sulforhodamine B Assay
2.3. Cell Proliferation by CFSE
2.4. Colony Formation Assay
2.5. Wound Healing Assessment Assay
2.6. Annexin V/PI Assay
2.7. Evaluation of ROS Levels
2.8. Fluorescence Staining Evaluation
2.9. Lysosomal Membrane Permeabilization Assessment
2.10. Intracellular pH Evaluation
2.11. Fluorescence Microscopy and Flow Cytometry General Considerations
2.12. Data Analysis
3. Results and Discussion
3.1. Biological Activity of the Benzo[a]phenoxazine Compounds C9, A36, and A42
3.1.1. Effect of C9, A36, and A42 on Cell Viability
3.1.2. C9, A36, and A42 Decrease RKO and MCF7 Cell Proliferation
3.1.3. C9, A36, and A42 Reduce Cell Migration of RKO and MCF7 Cells
3.1.4. C9, A36, and A42 Reduce RKO and MCF7 Cell Survival
3.1.5. C9, A36, and A42 Induce RKO and MCF7 Cell Death
3.2. Intracellular Target Evaluation of the Benzo[a]phenoxazine Compounds C9, A36, and A42
3.2.1. C9, A36, and A42 Accumulate and Emit Fluorescence on RKO and MCF7 Cell Lysosomes
3.2.2. C9, A36, and A42 Lysosomal Membrane Permeabilization, Cytosolic Acidification, and ROS Generation
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cell Lines | IC50 (μM) a ± SD b | Selectivity Index c | ||||
---|---|---|---|---|---|---|
BaP1 d | C9 | A36 | A42 | Cell Line IC50/BJ-5ta IC50 | CRC IC50/NCM460 IC50 | |
BJ-5ta e | 1.83 ± 0.06 | 2.55 ± 0.15 | 2.44 ± 0.18 | 2.58 ± 0.19 | ||
NCM460 e | 12.80 ± 2.05 | 1.12 ± 0.13 | 2.06 ± 0.25 | 2.59 ± 0.31 | ||
SW480 f | 5.60 ± 0.19 | 0.78 ± 0.09 | 0.72 ± 0.03 | 0.78 ± 0.07 | 0.33/3.27/3.38/3.31 | 2.28/1.44/2.86/3.32 |
HCT116 f | 1.90 ± 0.09 | 1.64 ± 0.09 | 1.28 ± 0.06 | 1.13 ± 0.07 | 0.97/1.55/1.91/2.25 | 6.73/0.68/1.61/2.29 |
RKO f | 1.40 ± 0.08 | 0.17 ± 0.01 | 0.37 ± 0.03 | 0.29 ± 0.01 | 1.30/15/6.59/8.9 | 9.14/6.59/5.56/8.93 |
MCF7 g | 0.92 ± 0.07 | 0.84 ± 0.06 | 0.63 ± 0.05 | 0.54 ± 0.02 | 1.9/3.04/3.86/4.80 | |
MDA-MB-231 g | 1.73 ± 0.03 | 1.19 ± 0.05 | 1.01 ± 0.09 | 0.79 ± 0.03 | 1.05/2.14/2.41/3.26 |
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Ferreira, J.C.C.; Gonçalves, M.S.T.; Preto, A.; Sousa, M.J. Anticancer Activity of Benzo[a]phenoxazine Compounds Promoting Lysosomal Dysfunction. Cells 2024, 13, 1385. https://doi.org/10.3390/cells13161385
Ferreira JCC, Gonçalves MST, Preto A, Sousa MJ. Anticancer Activity of Benzo[a]phenoxazine Compounds Promoting Lysosomal Dysfunction. Cells. 2024; 13(16):1385. https://doi.org/10.3390/cells13161385
Chicago/Turabian StyleFerreira, João Carlos Canossa, M. Sameiro T. Gonçalves, Ana Preto, and Maria João Sousa. 2024. "Anticancer Activity of Benzo[a]phenoxazine Compounds Promoting Lysosomal Dysfunction" Cells 13, no. 16: 1385. https://doi.org/10.3390/cells13161385