The Anti-Proliferative Activity of the Hybrid TMS-TMF-4f Compound Against Human Cervical Cancer Involves Apoptosis Mediated by STAT3 Inactivation
Abstract
:1. Introduction
2. Results
2.1. TMS-TMF-4f Suppresses the Proliferation of HeLa and CaSki Human Cervical Cancer Cells by Inducing Caspase-Dependent Apoptosis
2.2. TMS-TMF-4f Induces Mitochondria-Dependent Apoptosis by Regulating Bcl-2 Family Proteins
2.3. STAT3 is Involved in TMS-TMF-4f-Induced Apoptosis
2.4. TMS-TMF-4f Ameliorates IL-6-Induced STAT3 Activation in Human Cervical Cancer Cells
2.5. TMS-TMF-4f Docks into a Pocket Between the DNA-Binding and Ligand-Binding Domains of STAT3
2.6. TMS-TMF-4f Exhibits Significant Antitumor Effects in a Xenograft Cervical Cancer Mouse Model
2.7. TMS-TMF-4f Promotes Apoptosis and Attenuates STAT3 Activation in Cervical Tumor Tissues
3. Discussion
4. Materials and Methods
4.1. Synthesis of Hybrid Analogs
4.2. Cell Culture
4.3. Cell Viability Assay
4.4. Annexin V-FITC and PI double Staining Assay
4.5. Western Blot Analysis
4.6. Measurement of MMP
4.7. Preparation of Cytosolic Fraction
4.8. Immunocytochemistry
4.9. Transfection
4.10. Animals
4.11. In Vivo Tumor Xenograft Studies
4.12. Terminal Deoxynucleotidyl Transferase-Mediated dUTP μM Nick End Labeling (TUNEL) Assay
4.13. Molecular Docking Analysis
4.14. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
References
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Compound (TMS-TMF) | a IC50 (μM) | ||||
---|---|---|---|---|---|
HCT116 | A549 | AsPC-1 | HeLa | ||
4a | 38.27 ± 1.60 | 46.61 ± 3.12 | 39.11 ± 2.23 | 35.55 ± 2.54 | |
4b | 27.60 ± 7.55 | 27.86 ± 6.47 | 25.57 ± 6.48 | 14.21 ± 4.63 | |
4c | 36.27 ± 4.76 | 24.41 ± 2.49 | 31.41 ± 1.45 | 34.99 ± 1.70 | |
4d | 33.57 ± 5.38 | 41.85 ± 3.69 | >50 | >50 | |
4e | 30.54 ± 5.21 | >50 | >50 | >50 | |
4f | 17.33 ± 2.76 | 16.79 ± 3.85 | 14.68 ± 1.65 | 12.07 ± 1.84 | |
Etoposide | 21.45 ± 3.82 | 24.25 ± 2.99 | 29.77 ± 3.08 | 32.70 ± 2.56 |
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Share and Cite
Hong, J.Y.; Chung, K.-S.; Shin, J.-S.; Lee, J.-H.; Gil, H.-S.; Lee, H.-H.; Choi, E.; Choi, J.-H.; Hassan, A.H.E.; Lee, Y.S.; et al. The Anti-Proliferative Activity of the Hybrid TMS-TMF-4f Compound Against Human Cervical Cancer Involves Apoptosis Mediated by STAT3 Inactivation. Cancers 2019, 11, 1927. https://doi.org/10.3390/cancers11121927
Hong JY, Chung K-S, Shin J-S, Lee J-H, Gil H-S, Lee H-H, Choi E, Choi J-H, Hassan AHE, Lee YS, et al. The Anti-Proliferative Activity of the Hybrid TMS-TMF-4f Compound Against Human Cervical Cancer Involves Apoptosis Mediated by STAT3 Inactivation. Cancers. 2019; 11(12):1927. https://doi.org/10.3390/cancers11121927
Chicago/Turabian StyleHong, Joo Young, Kyung-Sook Chung, Ji-Sun Shin, Jeong-Hun Lee, Hyo-Sun Gil, Hwi-Ho Lee, Eunwoo Choi, Jung-Hye Choi, Ahmed H.E. Hassan, Yong Sup Lee, and et al. 2019. "The Anti-Proliferative Activity of the Hybrid TMS-TMF-4f Compound Against Human Cervical Cancer Involves Apoptosis Mediated by STAT3 Inactivation" Cancers 11, no. 12: 1927. https://doi.org/10.3390/cancers11121927