Antineoplastic Activity of Rhus trilobata Nutt. (Anacardiaceae) against Ovarian Cancer and Identification of Active Metabolites in This Pathology
Abstract
:1. Introduction
2. Results and Discussion
2.1. Biological Activity of AE-RHTR and Fractions in Cell Lines
2.2. Antineoplastic Activity of RHTR in Mice Xenotransplanted with SKOV-3 Cells
2.2.1. Imaging and Histopathological Studies of Tumor Lesions
2.2.2. Morphometric and Paraclinical Studies of Mice Treated with RHTR
2.3. Purified Metabolites in RHTR
2.4. Phytochemical Composition and in Silico Analysis of AF02-RHTR
2.5. Biological Activity of Active Metabolites from RHTR in Cell Lines
3. Materials and Methods
3.1. Chemicals and Reagents
3.2. Recollection of the Plant Material
3.3. Preparation of the Plant Extract and Fractionation
3.4. Purification and Identification of Metabolites
3.5. Cell Culture
3.6. Determination of Cell Viability by Formazan Salts
3.7. Measurement of Proliferation, Cytotoxicity, and Apoptosis in Cells
3.8. Evaluation of Cell Morphology
3.9. Experimental Animals
3.10. Imaging, Paraclinical, and Histopathologic Studies
3.11. Phytochemical Composition of the RHTR Active Fraction
3.12. In Silico Studies and Statistical Analysis
4. Conclusions
5. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
References
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Treatments | AE | AF02 | Carboplatin | 1× PBS |
---|---|---|---|---|
Weight (g) | 0.24 ± 0.09 * | 0.19 ± 0.10 * | 0.14 ± 0.06 * | 0.34 ± 0.09 |
Larger diameter (mm) | 9.07 ± 0.25 * | 7.40 ± 0.95 * | 3.70 ± 0.26 * | 14.53 ± 2.4 |
Tumor volume (mm3) | 201.4 ± 11.6 * | 172.7 ± 15.3 * | 137.3 ± 18.6 * | 373.3 ± 18.1 |
Attenuation coefficient (HU) | 47 ± 2.16 | 48.8 ± 0.83 | 48.7 ± 0.95 | 47 ± 2.1 |
Vascularity | + | + | + | +++ |
Fibrosis | + | + | + | + |
Morphology | Cystic | Cystic | Solid | Cystic |
Treatments | AE | AF02 | Carboplatin | 1× PBS | Reference Range (mean) |
---|---|---|---|---|---|
Glucose (mg/dL) | 72 ± 23.9 | 114 ± 21.2 * | 107 ± 14.8 * | 78.3 ± 16.6 | 63–176 (89) |
Triglycerides (mg/dL) | 71.5 ± 26.2 | 80 ± 11.35 | 103.7 ± 12.7 * | 87.6 ± 12.01 | 55–115 (85) |
Cholesterol (mg/dL) | 66 ± 25.4 * | 62 ± 2.52 * | 108.6 ± 19.4 * | 85.5 ± 13.4 | 26–82 (64) |
Protein (g/dL) | 4.48 ± 0.6 | 4.42 ± 0.62 | 5.1 ± 1.46 | 4.7 ± 0.56 | 4–8.6 (6.2) |
Albumin (g/dL) | 2.1 ± 0.8 * | 2.03 ± 0.35 * | 1.33 ± 0.29 | 1.36 ± 0.21 | 2.5–4 (3.2) |
AST (GOT) (U/L) | 132.6 ± 45.7 | 145.7 ± 7.69 | 162.9 ± 8.2 | 149.8 ± 27.29 | 55–251 (139) |
ALT (GPT) (U/L) | 41.2 ± 9.8 | 32.43 ± 19.2 | 64.4 ± 6.87 * | 40.75 ± 14.5 | 17–77 (47) |
Total bilirubin (mg/dL) | 0.47 ± 0.07 * | 0.39 ± 0.08 * | 0.58 ± 0.2 | 0.67 ± 0.16 | 0.20–1.0 (0.6) |
Alkaline phosphatase (U/L) | 46.5 ± 23.2 * | 83.6 ± 24.04 | 66.6 ± 15.6 | 71 ± 10.36 | 9–88 (48.5) |
Creatinine (mg/dL) | 0.74 ± 0.4 | 0.7 ± 0.25 | 0.37 ± 0.26 * | 0.65 ± 0.2 | 0.2–0.9 (0.5) |
Urea (mg/dL) | 40.8 ± 8.2 | 57.6 ± 10.7 | 59.4 ± 9.99 | 47.9 ± 7.16 | 46.9–73 (60.1) |
BUN (g/dL) | 19 ± 3.8 | 26.8 ± 4.7 | 27.8 ± 4.63 | 22.36 ± 3.32 | 11–27 (19) |
Hemoglobin (g/dL) | 15.2 ± 0.98 | 12.35 ± 2.2 | 13.1 ± 1.61 | 14.4 ± 2.13 | 10–17 (13.1) |
Hematocrit (%) | 48.3 ± 7.92 | 43.6 ± 17.8 | 40.57 ± 4.16 | 44.52 ± 2.17 | 39–49 (40.4) |
Erythrocytes (×106/mm3) | 7.24 ± 1.06 | 7.67 ± 2.26 | 7.81 ± 0.88 | 7.92 ± 1.93 | 8.3 |
Leukocytes (×100/mm3) | 3600 ± 903 * | 4242.6 ± 980 | 2750 ± 777 * | 5720 ± 684 | 5–12 (6.33) |
Platelets (×106/μL) | 736 ± 1.414 | 689 ± 5.425 | 759 ± 19.143 | 710 ± 6.716 | 116 |
PCT | 0.53 ± 0.07 | 0.49 ± 0.10 | 0.55 ± 0.29 | 0.55 ± 0.30 | -- |
No. | RT (min) | PI | Compound Name | Biological Activity | Presence in Plants | DLMS |
---|---|---|---|---|---|---|
1 | 6.18 | HMDB41635 | myricetin 3-arabinoside | Antioxidant, anticarcinogenic | Rhus spp. | 0.90 |
2 | 6.44 | CSID70398 | methyl gallate * | Antioxidant | Rhus spp. | −0.49 |
3 | 7.05 | HMDB38831 | epigallocatechin 3-cinnamate | Antioxidant, antibacterial | Ocotea porosa | 0.24 |
4 | 7.36 | CSID3525015 | 3,5-digalloylepicatechin | Antioxidant | -- | 1.52 |
5 | 8.27 | CHEBI:18152 | myricetin * | Antioxidant, antineoplastic | Rhus spp. | −0.04 |
6 | 8.47 | LMPK12112436 | myricitrin * | Antioxidant, antineoplastic | Rhus spp. | 0.78 |
7 | 8.52 | LMPK12110568 | quercetin 3-(2’’’-galloylglucosyl)-(1→2)-alpha-L-arabinofuranoside | Antioxidant | Euphorbia pachyrhiza | 1.24 |
8 | 8.52 | CHEBI18082 | 1,2,3,4,6-pentakis-O-galloyl-β-D-glucose | Antineoplastic | Rhus spp. | 0.35 |
9 | 8.60 | CHEBI:16243 | quercetin * | Antioxidant, anti-inflammatory, antineoplastic | Rhus spp. | 0.93 |
10 | 9.13 | CSID24784962 | 4-O-digalloyl-1,2,3,6-tetra-O-β-D-galloylglucose | Antibacterial, antineoplastic, antithrombotic | Rhus typhina | 0.35 |
11 | 9.45 | CHEBI:5715 | hibiscoquinone a | Antioxidant | Hibiscus spp. | −0.52 |
12 | 9.45 | LMPK12112171 | quercitrin * | Antioxidant, antineoplastic | Rhus spp. | 1.04 |
13 | 9.96 | LMPK12112447 | myricetin 3-(4’’-galloylrhamnoside) | Antioxidant | -- | 1.12 |
14 | 10.20 | LMPK12100067 | obtusaquinol | Antiparasitic, nitric oxide inhibitor | Dalbergia spp. | −0.03 |
15 | 10.94 | CSID35013429 | epifisetinidol-(4β→8)-catechin | Antibacterial, α-amylase and lipase inhibitor | Cotinus coggyria | 0.61 |
16 | 11.92 | LMPK12111566 | fisetin * | Antineoplastic, antioxidant, antiangiogenic | Rhus spp. | 0.76 |
17 | 12.54 | LMFA01010048 | margaric acid | Antioxidant, antifungal | Rhus typhina | −0.33 |
18 | 12.54 | LMFA01050146 | 12S-hydroxy-16-heptadecynoic acid | Anti-inflammatory | -- | −0.38 |
19 | 13.37 | CSID8034429 | (-)-pinellic acid | Metabolism, adjuvant activity | Pinelliae tuber | −1.08 |
20 | 13.37 | LMFA01030130 | 11,14-eicosadienoic acid | Antioxidant, anti-inflammatory | Rhus typhina | −0.08 |
21 | 13.9 | LMPK12040009 | amentoflavone | Antioxidant, anti-inflammatory | Rhus spp. | 0.51 |
22 | 15.94 | CSID10297786 | 3-(1,1-dimethylallyl)-8-(3,3-dimethylallyl) xanthyletin | -- | Ruta graveolens | −1.31 |
23 | 17.7 | CHEBI:31014 | lignocerate | Anti-inflammatory | Oleandra neriiformis | −0.33 |
24 | 21.28 | LMFA02000057 | 2R-hydroxy-9Z,12Z-octadecadienoic acid | Anti-allergic | Brassica campestris | −0.96 |
Sample/Cell Line | SKOV-3 | OVCAR-3 | CACO-2 | BEAS-2B | CHO-K1 |
---|---|---|---|---|---|
Gallic acid | 50 (294) | 43 (253) | 25 (147) | 25 (147) | 100 (588) |
Methyl gallate | >200 (1,086) | >200 (1,086) | 100 (543) | 200 (1,086) | 130 (706) |
Myricetin | 166 (522) | 94 (295) | 62 (195) | 64 (201) | 33 (104) |
Myricitrin | 197 (424) | 200 (431) | >200 (431) | 160 (344) | 94 (202) |
Quercetin | >200 (662) | 200 (662) | 150 (496) | 189 (625) | 127 (420) |
Quercitrin | >200 (446) | >200 (446) | 179 (399) | >200 (446) | >200 (446) |
Fisetin | 200 (699) | 200 (699) | 100 (349) | 50 (175) | 46 (161) |
Paclitaxel | 7 (8.20) | 8 (9.37) | 20 (23.42) | 8 (9.37) | 10 (11.71) |
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Varela-Rodríguez, L.; Sánchez-Ramírez, B.; Saenz-Pardo-Reyes, E.; Ordaz-Ortiz, J.J.; Castellanos-Mijangos, R.D.; Hernández-Ramírez, V.I.; Cerda-García-Rojas, C.M.; González-Horta, C.; Talamás-Rohana, P. Antineoplastic Activity of Rhus trilobata Nutt. (Anacardiaceae) against Ovarian Cancer and Identification of Active Metabolites in This Pathology. Plants 2021, 10, 2074. https://doi.org/10.3390/plants10102074
Varela-Rodríguez L, Sánchez-Ramírez B, Saenz-Pardo-Reyes E, Ordaz-Ortiz JJ, Castellanos-Mijangos RD, Hernández-Ramírez VI, Cerda-García-Rojas CM, González-Horta C, Talamás-Rohana P. Antineoplastic Activity of Rhus trilobata Nutt. (Anacardiaceae) against Ovarian Cancer and Identification of Active Metabolites in This Pathology. Plants. 2021; 10(10):2074. https://doi.org/10.3390/plants10102074
Chicago/Turabian StyleVarela-Rodríguez, Luis, Blanca Sánchez-Ramírez, Erika Saenz-Pardo-Reyes, José Juan Ordaz-Ortiz, Rodrigo Daniel Castellanos-Mijangos, Verónica Ivonne Hernández-Ramírez, Carlos Martín Cerda-García-Rojas, Carmen González-Horta, and Patricia Talamás-Rohana. 2021. "Antineoplastic Activity of Rhus trilobata Nutt. (Anacardiaceae) against Ovarian Cancer and Identification of Active Metabolites in This Pathology" Plants 10, no. 10: 2074. https://doi.org/10.3390/plants10102074