Antineoplastic Activity of 9″-Lithospermic Acid Methyl Ester in Glioblastoma Cells
Abstract
:1. Introduction
2. Results
2.1. Sensitivity of Glioblastoma Cells to 9″-Lithospermic Acid Methyl Ester and IC50 Calculation
2.2. 9″-Lithospermic Acid Methyl Ester Induces Cell Cycle Arrest
2.3. 9″-Lithospermic Acid Methyl Ester Inhibits the Migration of Glioblastoma Cells
2.4. 9″-Lithospermic Acid Methyl Ester and TMZ Exert Synergistic Anti-Proliferative Results
3. Discussion
4. Materials and Methods
4.1. Isolation and Identification of 9″-Lithospermic Acid Methyl Ester
4.2. Cell Lines and Treatment Conditions
4.3. Trypan Blue Assay
4.4. Crystal Violet Assay
4.5. Flow Cytometric Analysis of DNA Cell Cycle
4.6. Combination Treatment with 9″-Lithospermic Acid Methyl Ester and Temozolomide
4.7. Scratch Wound Healing Assay
4.8. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
CI | Combination Index |
DMSO | Dimethyl Sulfoxide |
FBS | Fetal Bovine Serum |
GBM | Glioblastoma |
HIV | Human Immunodeficiency Virus |
PBS | Phosphate-Buffered Saline |
PI | Propidium Iodide |
PI3K | Phosphoinositide 3—kinase |
TMZ | Temozolomide |
References
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Agent Concentration | Sub. G0/G1 | G0/G1 | S | G2/M | |
---|---|---|---|---|---|
U87 | Control | 0.7% ± 0.20% | 75.1% ± 1.90% | 18.1% ± 1.15% | 3.4% ± 0.35% |
IC50 | 2.8% ± 0.25% | 63.7% ± 1.10% | 24.6% ± 3.53% | 5.6% ± 1.22% | |
2IC50 | 12.2% ± 1.00% | 51.8% ± 1.59% | 27.0% ± 2.52% | 6.3% ± 0.61% | |
T98 | Control | 1.2% ± 0.26% | 67.6% ± 1.34% | 17.3% ± 1.01% | 11.8% ± 0.06% |
IC50 | 14.1% ± 0.42% | 44.2% ± 0.50% | 23.6% ± 0.82% | 13.2% ± 0.38% | |
2IC50 | 29.3% ± 2.98% | 30.5% ± 3.00% | 23.8% ± 0.93% | 11.1% ± 0.42% |
U87 | ||||
9″–LITH (μM) | TMZ (μM) | EFFECT | CI | RESULT |
30.0 | 50.0 | 0.9251 | 0.75558 | SYNERGY |
15.0 | 25.0 | 0.8682 | 0.64668 | SYNERGY |
45.0 | 50.0 | 0.9432 | 0.64868 | SYNERGY |
60.0 | 100.0 | 0.9742 | 0.58751 | SYNERGY |
T98 | ||||
9″–LITH (μM) | TMZ (μM) | EFFECT | CI | RESULT |
34.0 | 300.0 | 0.8702 | 1.4817 | ANTAGONISM |
17.0 | 200.0 | 0.8702 | 0.8881 | SYNERGY |
51.0 | 300.0 | 0.9441 | 1.323 | ANTAGONISM |
68.0 | 400.0 | 0.9664 | 1.4882 | ANTAGONISM |
No | δC | Type C | δH | H | J (Hz) |
---|---|---|---|---|---|
1 | 127.5 | C | - | - | - |
2 | 130.1 | C | - | - | - |
3 | 150.6 | C | - | - | - |
4 | 146.9 | C | - | - | - |
5 | 118.1 | CH | 7.01 | 1 | d (J = 8.0) |
6 | 121.9 | CH | 7.06 | 1 | d (J = 8.0) |
7 | 145.9 | CH | 7.54 | 1 | d (J = 16.0) |
8 | 116.3 | CH | 6.30 | 1 | d (J = 16.0) |
9 | 168.9 | C=O | - | - | - |
1′ | 131.2 | C | - | - | - |
2′ | 117.4 | CH | 6.78 | 1 | br s |
3′ | 146.6 | C | - | - | - |
4′ | 144.8 | C | - | - | - |
5′ | 116.5 | CH | 6.68 | 1 | d (J = 8.5) |
6′ | 118.8 | CH | 6.63 | 1 | br dd (J = 8.5) |
7′a | 38.7 | CH2 | 3.11 | 1 | br dd (J = 13.7, 3.4) |
7′b | 2.96 | 1 | dd (J = 13.7, 9.8) | ||
8′ | 77.5 | CH | 5.13 | 1 | br dd (J = 9.8, 3.4) |
9′ | 177.4 | C=O | - | - | - |
1″ | 133.2 | C | - | - | - |
2″ | 114.1 | CH | 6.82 | 1 | br s |
3″ | 146.3 | C | - | - | - |
4″ | 143.0 | C | - | - | - |
5″ | 116.7 | CH | 6.77 | 1 | d (J = 8.5) |
6″ | 117.7 | CH | 6.72 | 1 | dd (J = 8.5, 1.9) |
7″ | 88.5 | CH | 5.94 | 1 | d (J = 7.0) |
8″ | 57.0 | CH | 4.28 | 1 | d (J = 6.8) |
9″ | 172.9 | C=O | - | - | - |
-OCH3 | 53.3 | CH3 | 3.80 | 3 | s |
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Tzitiridou, P.; Zoi, V.; Papagrigoriou, T.; Lazari, D.; Sioka, C.; Alexiou, G.A.; Kyritsis, A.P. Antineoplastic Activity of 9″-Lithospermic Acid Methyl Ester in Glioblastoma Cells. Int. J. Mol. Sci. 2024, 25, 2094. https://doi.org/10.3390/ijms25042094
Tzitiridou P, Zoi V, Papagrigoriou T, Lazari D, Sioka C, Alexiou GA, Kyritsis AP. Antineoplastic Activity of 9″-Lithospermic Acid Methyl Ester in Glioblastoma Cells. International Journal of Molecular Sciences. 2024; 25(4):2094. https://doi.org/10.3390/ijms25042094
Chicago/Turabian StyleTzitiridou, Panagiota, Vasiliki Zoi, Theodora Papagrigoriou, Diamanto Lazari, Chrissa Sioka, Georgios A. Alexiou, and Athanassios P. Kyritsis. 2024. "Antineoplastic Activity of 9″-Lithospermic Acid Methyl Ester in Glioblastoma Cells" International Journal of Molecular Sciences 25, no. 4: 2094. https://doi.org/10.3390/ijms25042094