Tannic Acid and Ethyl Gallate Potentialize Paclitaxel Effect on Microtubule Dynamics in Hep3B Cells
Abstract
:1. Introduction
2. Results
2.1. TA and EG Treatment Enhance the Inhibitory Effect of PTX on the Viability of Hep3B HCC Cancer Cells
2.2. TA and EG Treatment Potentiates the Effect of PTX on Microtubule Stabilization and the G2/M Phase of the Cell Cycle in HEP3B Cells
2.3. Modulation of Tubulin Assembly by Ligand
2.4. Biochemical Characterization of TA and Tubulin Interaction
2.5. Taxane Displacement Assay
2.6. Molecular Docking of TA and EG to Tubulin
2.7. Effect of TA, EG, and PTX on Protein Kinase Activity
3. Discussion
4. Materials and Methods
4.1. Cell Culture
4.2. Cell Cytotoxicity Assay
4.3. Indirect Immunofluorescence
4.4. Cell Cycle Analysis
4.5. Ligand-Induced Tubulin Assembly
4.6. Biochemical Characterization of TA and Tubulin Interaction
4.7. Taxane Displacement Assay
4.8. Molecular Docking
4.9. Western Blotting
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Ligand | Affinitty Energy (Kcal/mol) |
---|---|
PTX (62%) a | −9.0 +/− 0.2 |
TA (cluster 1) (30%) a | −8.6 +/− 0.5 |
TA (cluster 2) (20%) a | −8.4 +/− 0.4 |
EG (77%) a | −6.5 +/− 0.1 |
Ligand | Affinitty Energy (Kcal/mol) |
---|---|
Tannic Acid (23%) a | −8.7 +/− 0.6 |
Ethyl Gallate (68%) a | −6.5 +/− 0.1 |
Residue | Tubulin | 1JFF | REDOCKING | TA | TA + PTX | EG | EG + PTX | Ligands [27] |
---|---|---|---|---|---|---|---|---|
VAL74 | α | * | * | * | ||||
GLU77 | α | * | * | * | ||||
VAL78 | α | * | * | * | ||||
THR80 | α | * | ||||||
GLY81 | α | * | * | * | ||||
THR82 | α | * | * | * | ||||
ARG221 | α | * | ||||||
THR223 | α | * | * | * | ||||
TYR224 | α | * | * | * | ||||
THR225 | α | * | * | * | ||||
ASN226 | α | * | ||||||
ASN228 | α | * | * | * | ||||
ARG229 | α | * | ||||||
LYS19 | β | * | L2 | |||||
GLU22 | β | * | * | * | L2 | |||
VAL23 | β | * | * | * | L2, L3, PTX | |||
ILE24 | β | * | ||||||
SER25 | β | * | ||||||
ASP26 | β | * | * | * | PTX | |||
GLU27 | β | * | * | * | L2, L3 | |||
GLY29 | β | * | ||||||
ILE30 | β | * | ||||||
ASP31 | β | * | ||||||
PRO32 | β | * | ||||||
HIS37 | β | * | ||||||
ASP39 | β | * | ||||||
SER40 | β | * | ||||||
ASP41 | β | * | ||||||
LEU42 | β | * | ||||||
GLN43 | β | * | ||||||
GLU47 | β | * | ||||||
GLU55 | PTX | |||||||
PHE83 | β | * | * | |||||
CYS213 | β | * | L1, L2, L3 | |||||
LEU217 | β | * | * | * | L1, L2, L3, PTX | |||
LYS218 | β | * | ||||||
LEU219 | β | * | * | L1, L2, L3, PTX | ||||
THR220 | β | * | ||||||
THR221 | β | * | ||||||
ASP226 | β | * | * | L1, L2, L3, EPOA | ||||
ASN228 | β | ZMP | ||||||
HIS229 | β | * | * | * | L1, L2, L3, PTX, ZMP | |||
LEU230 | β | * | * | * | L1, L2, L3, PTX | |||
SER232 | β | * | L2 | |||||
ALA233 | β | * | * | * | L1, L2, L3, PTX | |||
SER236 | β | * | * | * | L2, L3, PTX | |||
GLY237 | β | * | L2 | |||||
PRO245 | β | * | ||||||
GLY246 | β | * | * | * | ||||
GLN247 | β | * | * | * | ||||
ASN249 | β | * | ||||||
PHE272 | β | * | * | * | L1, L2, L3, PTX | |||
PRO274 | β | * | * | * | L1, L2, L3, PTX | |||
LEU275 | β | * | * | * | L1, L2, L3, PTX | |||
THR276 | β | * | * | * | L1, L2, L3, PTX, EPOA, ZMP | |||
SER277 | β | * | * | * | L1, L2, L3, PTX | |||
ARG278 | β | * | * | * | L1, L2, L3, PTX | |||
GLY279 | β | * | ||||||
SER280 | β | * | ||||||
GLN281 | β | * | PTX, EPOA | |||||
GLN282 | β | * | L3 | |||||
TYR283 | β | * | ||||||
ARG284 | β | * | PTX | |||||
LEU286 | β | * | PTX | |||||
THR287 | β | * | ||||||
VAL288 | β | * | ||||||
LEU291 | β | PTX | ||||||
GLN294 | β | PEL | ||||||
PHE296 | β | LAU, PEL | ||||||
ASP297 | β | PEL | ||||||
ALA298 | β | PEL | ||||||
PRO307 | β | PEL | ||||||
ARG308 | β | LAU, PEL | ||||||
TYR312 | β | LAU, PEL | ||||||
ARG320 | β | * | * | * | L2, L3 | |||
GLY321 | β | * | ||||||
ARG322 | β | * | * | * | ||||
MET323 | β | * | ||||||
SER324 | β | * | ||||||
GLU327 | β | * | ||||||
VAL335 | β | LAU, PEL | ||||||
ASN339 | β | LAU, PEL | ||||||
SER341 | β | LAU | ||||||
TYR342 | β | LAU, PEL | ||||||
PHE343 | β | LAU | ||||||
ILE347 | β | LAU | ||||||
ASP357 | β | * | * | |||||
ILE358 | β | * | ||||||
PRO359 | β | * | ||||||
PRO360 | β | * | * | * | * | L2, L3, PTX | ||
ARG369 | β | * | * | * | * | L1, L2, L3, PTX | ||
GLY370 | β | * | * | * | * | L1, L2, L3, PTX | ||
LEU371 | β | * | * | * | L1, L2, L3, PTX | |||
LYS372 | β | * | * | |||||
MET373 | β | * | * | |||||
SER374 | β | PTX |
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Sánchez-Carranza, J.N.; Redondo-Horcajo, M.; Barasoain, I.; Escobar-Aguilar, E.A.; Millán-Pacheco, C.; Alvarez, L.; Salas Vidal, E.; Diaz, J.F.; Gonzalez-Maya, L. Tannic Acid and Ethyl Gallate Potentialize Paclitaxel Effect on Microtubule Dynamics in Hep3B Cells. Pharmaceuticals 2023, 16, 1579. https://doi.org/10.3390/ph16111579
Sánchez-Carranza JN, Redondo-Horcajo M, Barasoain I, Escobar-Aguilar EA, Millán-Pacheco C, Alvarez L, Salas Vidal E, Diaz JF, Gonzalez-Maya L. Tannic Acid and Ethyl Gallate Potentialize Paclitaxel Effect on Microtubule Dynamics in Hep3B Cells. Pharmaceuticals. 2023; 16(11):1579. https://doi.org/10.3390/ph16111579
Chicago/Turabian StyleSánchez-Carranza, Jessica Nayelli, Mariano Redondo-Horcajo, Isabel Barasoain, Ever Angel Escobar-Aguilar, César Millán-Pacheco, Laura Alvarez, Enrique Salas Vidal, J. Fernando Diaz, and Leticia Gonzalez-Maya. 2023. "Tannic Acid and Ethyl Gallate Potentialize Paclitaxel Effect on Microtubule Dynamics in Hep3B Cells" Pharmaceuticals 16, no. 11: 1579. https://doi.org/10.3390/ph16111579