Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches
Abstract
:1. Introduction
2. Results
2.1. Plant Material
2.2. Establishment of In Vitro Culture
2.3. Cytotoxic Activities of the Different Tested Alkaloid Fractions
2.4. Alkaloid Profile of the Different Alkaloid Fractions
2.5. Multivariate Analyses of the Cytotoxic Activities of the Alkaloid Fractions
2.6. Molecular Docking Analysis
3. Discussion
3.1. In Vitro Propagation
3.2. Alkaloid Fractions Differed in Alkaloid Profiles and Cytotoxic Activities
4. Materials and Methods
4.1. Plant Material
4.2. Micropropagation of Amaryllidaceae Species
4.3. Extraction of Alkaloids
4.4. Alkaloid Analyses by GC/MS
Data Processing and Analysis
4.5. Cell Viability Screening of Alkaloid Fractions
4.5.1. Cell Culture
4.5.2. ATP Quantification by Bioluminescence
4.5.3. Mitochondrial MTT Reduction
4.6. In-Silico Analysis
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Species | Origin Georeference | Voucher |
---|---|---|
C. jagus 1 | 6°9′33.58″ N, 75°21′32.75″ W 2120 m; Marinilla-Antioquia | 5270 Alzate |
C. subedentata 2 | 2°32′27″ N, 76°37′44″ O. 1692 m; Popayan-Cauca | 5400 Alzate |
C. tenera 2 | 2°32′27″ N, 76°37′44″ O. 1692 m; Popayan-Cauca | 5400 Alzate |
E. bonplandii 1 | 4°35′18.47″ N, 75°51′19.78″ W. 1150 m; Armenia-Quindío | 5107 Alzate |
E. caucana 2 | 5°29′54″ N, 76°32′29″ O. 69 m; Lloró, Chocó | 5168 Alzate |
E. formosa 2 | 2°32′27″ N, 76°37′44″ O. 1692 m; Popayan-Cauca | 5401 Alzate |
P. lehmannii 1 | 2°4′27″ N, 76º 54′1′′ O, 1610 m; Rosas-Cauca | 5106 Alzate |
P. ventricosa 1 | 1°12′29″ N,77°27′57″ O, 1663 m; Consaca-Nariño | 5402 Alzate |
Z. carinata 1 | 6°4′30.37″ N, 75°22′46.00″ W, 2150 m; Carmen del Viboral-Antioquia | 5307 Alzate |
Z. puertoricensis 1 | 4°26′54″ N 75°11′56″ O; Ibagué-Tolima | 5308 Alzate |
Species | Cell Viability (%) 1 | ||||||
---|---|---|---|---|---|---|---|
AGS | PC3 | MCF-7 | MDA-MB 231 | BT-549 | HEC-1B | HaCat | |
C. jagus | 48.06 ± 3.35 | 73.42 ± 3.90 | 83.91 ± 1.15 | 58.88 ± 6.15 | 73.64 ± 3.38 | 87.65 ± 6.52 | 91.94 ± 0.83 |
C. subedentata | 52.15 ± 2.10 | 84.29 ± 3.48 | 98.05 ± 5.53 | 56.51 ± 0.62 | 77.67 ± 3.12 | 88.09 ± 5.90 | 99.49 ± 0.09 |
C. tenera | 73.72 ± 5.90 | 86.41 ± 2.28 | 73.94 ± 8.31 | 58.26 ± 8.12 | 65.28 ± 2.17 | 84.54 ± 0.88 | 99.11 ± 2.76 |
E. bonplandii | 45.79 ± 3.05 | 77.92 ± 3.91 | 90.61 ± 4.94 | 57.56 ± 2.99 | 69.43 ± 5.76 | 88.25 ± 4.38 | 94.27 ± 1.28 |
E. caucana | 61.46 ± 5.30 | 80.43 ± 3.79 | 52.82 ± 2.36 | 62.35 ± 4.35 | 65.51 ± 4.24 | 87.88 ± 4.91 | 99.57 ± 1.63 |
E. formosa | 54.18 ± 2.56 | 74.02 ± 5.60 | 94.93 ± 3.41 | 54.81 ± 4.61 | 62.36 ± 6.46 | 80.38 ± 8.46 | 88.26 ± 0.86 |
P. lehmannii | 71.90 ± 11.74 | 88.54 ± 2.34 | 73.28 ± 3.75 | 70.87 ± 4.27 | 76.40 ± 7.43 | 87.41 ± 1.49 | 98.32 ± 2.94 |
P. ventricosa | 80.41 ± 6.28 | 88.91 ± 4.49 | 98.38 ± 4.28 | 73.69 ± 4.58 | 86.11 ± 2.75 | 83.78 ± 6.63 | 98.34 ± 2.97 |
Z. carinata | 70.33 ± 8.91 | 88.40 ± 2.10 | 75.29 ± 7.44 | 72.46 ± 4.32 | 62.84 ± 5.37 | 78.29 ± 1.13 | 99.55 ± 4.78 |
Z. puertoricensis | 67.25 ± 1.90 | 74.76 ± 5.88 | 69.86 ± 3.58 | 56.02 ± 5.63 | 51.40 ± 1.42 | 75.95 ± 2.18 | 97.33 ± 6.69 |
Species 1 | Alkaloids Type (mg/gDW) 2 | |||||||
---|---|---|---|---|---|---|---|---|
Crinane | Galanthamine | Lycorine | Miscellaneous | |||||
C. jagus | Crinine (X1) Crinane acetate (X3) Buphanidrine (X5) Crinamine (X7) Powelline (X9) | 0.073 0.006 0.002 0.033 0.050 | 5,6-Dihydrobicolorine (X13) Anhydrolycorine (X15) 11,12-Dehydroanhydrolycorine (X19) Lycorine (X31) | 0.009 0.090 0.022 0.295 | Trisphaeridine (X22) | 0.026 | ||
C. subedentata | Crinine (X1) 8-O-Demethylmaritidine (X2) 6-O-Methylpretazettine (X4) Haemantamine (X6) Tazettine (X8) Hamayne (X10) | 0.216 1.700 0.022 1.005 0.211 0.771 | Galanthamine (X12) | 1.824 | 5,6-Dihydrobicolorine (X13) Anhydrolycorine (X15) Assoanine (X20) 11,12-Dehydroanhydrolycorine (X19) Lycorine (X31) | 0.069 0.279 0.038 0.210 0.629 | Ismine (X21) Trisphaeridine (X22) | 0.032 0.140 |
C. tenera | Crinine (X1) 8-O-Demethylmaritidine (X2) Haemantamine (X6) Tazettine (X8) Hamayne (X10) | 0.133 0.282 1.114 0.010 0.377 | Galanthamine (X12) | 0.055 | 5,6-Dihydrobicolorine (X13) 11,12-Dehydrolycorene (X16) 11,12-Dehydroanhydrolycorine (X19) Lycorine (X31) Pseudolycorine (X26) | 0.372 0.020 0.312 0.167 0.009 | Trisphaeridine (X22) Demethylismine (X23) | 0.371 0.018 |
E. bonplandii | Crinine (X1) 8-O-Demethylmaritidine (X2) Hamayne (X10) | 0.018 0.339 0.066 | Galanthamine (X12) Sanguinine (X14) Epinorgalanthamine (X17) | 0.280 0.004 0.006 | 5,6-Dihydrobicolorine (X13) Anhydrolycorine (X15) 11,12-Dehydroanhydrolycorine (X19) Lycorine (X31) Pseudolycorine (X26) | 0.003 0.056 0.008 0.581 0.004 | Trisphaeridine (X22) | 0.008 |
E. caucana | Crinine (X1) 8-O-Demethylmaritidine (X2) 6-O-Methylpretazettine (X4) Tazettine (X8) Hamayne (X10) | 0.013 0.015 0.012 0.045 0.324 | Galanthamine (X12) Sanguinine (X14) Narwedine (X18) N-formylnorgalanthamine (X25) | 0.181 0.434 0.010 0.027 | Anhydrolycorine (X15) 11,12-Dehydroanhydrolycorine (X19) Lycorine (X31) | 0.025 0.065 0.135 | Ismine (X21) Galanthindole (X24) | 0.008 0.016 |
E. formosa | 8-O-Demethylmaritidine (X2) Haemantamine (X6) Tazettine (X8) Hamayne (X10) | 0.068 0.315 0.019 0.247 | Galanthamine (X12) Sanguinine (X14) | 0.921 0.012 | 5,6-Dihydrobicolorine (X13) Lycorine (X31) | 0.010 2.390 | Ismine (X21) Trisphaeridine (X22) | 0.004 0.032 |
P. lehmannii | 8-O-Demethylmaritidine (X2) | 0.015 | Galanthamine (X12) Sanguinine (X14) | 0.015 0.004 | Lycorine (X31) Pseudolycorine (X26) | 0.090 0.029 | ||
P. ventricosa | Hamayne (X10) Deacetylcantabricine (X11) | 0.036 0.018 | Galanthamine (X12) | 0.015 | 11,12-Dehydroanhydrolycorine (X19) | 0.013 | Trisphaeridine (X22) | 0.017 |
Z. carinata | Crinine (X1) 8-O-Demethylmaritidine (X2) Haemantamine (X6) Tazettine (X8) | 0.718 0.138 1.707 0.417 | Galanthamine (X12) Lycoramine (X27) | 0.354 2.274 | 5,6-Dihydrobicolorine (X13) 11,12-Dehydrolycorene (X16) Anhydrolycorine (X15) 11,12-Dehydroanhydrolycorine (X19) Galanthine (X30) | 0.269 0.011 0.197 0.450 1.380 | Ismine (X21) Galanthindole (X24) Trisphaeridine (X22) | 0.075 0.105 0302 |
Z. puertoricensis | Deacetylcantabricine (X11) Aulicine (X28) | 0.021 0.006 | Sanguinine (X14) Norlycoramine (X29) | 0.003 0.006 | Anhydrolycorine (X15) Assoanine (X20) 11,12-Dehydroanhydrolycorine (X19) Lycorine (X31) | 0.030 0.004 0.006 0.099 |
Estimated Free Energy of Binding 1 | |||||
---|---|---|---|---|---|
Alkaloid Type | Compound | Bcl-2 | Mcl-1 | Bcl-xL | HK2 |
Lycorine | 5,6-dihydrobicolorine | −5.65 | −4.18 | −6.46 | −6.69 |
Anhydrolycorine | −5.79 | −5.01 | −6.23 | −6.83 | |
Assoanine | −5.63 | −5.02 | −5.66 | −6.62 | |
Lycorine | −5.75 | −3.85 | −4.77 | −8.25 | |
11,12-Dehydroanhydrolycorine | −5.57 | −5.58 | −6.79 | −6.69 | |
Pseudolycorine | −5.79 | −3.51 | −4.24 | −8.48 | |
Crinane | 8-O-demethylmaritidine | −6.40 | −3.62 | −4.71 | −7.61 |
Buphanidrine | −6.35 | −4.05 | −5.04 | −8.59 | |
Crinamin | −5.80 | −4.32 | −5.95 | −7.64 | |
Crinane acetate | −6.55 | −4.34 | −5.15 | −8.01 | |
Crinine | −6.00 | −4.78 | −5.33 | −8.26 | |
Haemanthamine | −5.70 | −4.71 | −5.50 | −7.75 | |
Hamayne | −6.02 | −3.57 | −4.83 | −7.66 | |
Powelline | −6.10 | −3.98 | −6.93 | −8.80 | |
Tazettine | −6.53 | −4.74 | −4.74 | −7.76 | |
6-O-Methylpretazettine | −6.53 | −3.31 | −4.64 | −8.38 | |
Deacetylcantabricine | −5.88 | −5.82 | −6.76 | −6.90 | |
Aulicine | −5.46 | −4.95 | −6.20 | −7.72 | |
Galanthamine | Galanthamine | −5.78 | −3.67 | −4.91 | −7.23 |
Sanguinine | −5.87 | −3.84 | −5.16 | −7.54 | |
Epinorgalanthamine | −6.56 | −4.63 | −6.64 | −7.87 | |
Narwedine | −6.34 | −4.16 | −5.46 | −7.65 | |
N-formylnorgalanthamine | −5.64 | −4.83 | −6.23 | −6.01 | |
Norlycoramine | −6.27 | −5.39 | −6.99 | −7.63 | |
Miscellaneous | Ismine | −5.48 | −3.67 | −4.01 | −6.43 |
Trisphaeridine | −5.69 | −4.57 | −5.55 | −6.41 | |
Galanthindole | −5.57 | −4.54 | −4.89 | −7.03 | |
Control | Obatoclax 2 | −6.76 | −4.62 | −5.77 | −7.64 |
Doxorubicin 2 | −5.66 | −3.48 | −6.74 | −8.35 |
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Trujillo, L.; Bedoya, J.; Cortés, N.; Osorio, E.H.; Gallego, J.-C.; Leiva, H.; Castro, D.; Osorio, E. Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches. Molecules 2023, 28, 2601. https://doi.org/10.3390/molecules28062601
Trujillo L, Bedoya J, Cortés N, Osorio EH, Gallego J-C, Leiva H, Castro D, Osorio E. Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches. Molecules. 2023; 28(6):2601. https://doi.org/10.3390/molecules28062601
Chicago/Turabian StyleTrujillo, Lina, Janeth Bedoya, Natalie Cortés, Edison H. Osorio, Juan-Carlos Gallego, Hawer Leiva, Dagoberto Castro, and Edison Osorio. 2023. "Cytotoxic Activity of Amaryllidaceae Plants against Cancer Cells: Biotechnological, In Vitro, and In Silico Approaches" Molecules 28, no. 6: 2601. https://doi.org/10.3390/molecules28062601