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. 2018 Nov 27;19(12):3765.
doi: 10.3390/ijms19123765.

Apoptosis Induction of Agave lechuguilla Torrey Extract on Human Lung Adenocarcinoma Cells (SK-LU-1)

Luis Alberto Anguiano-Sevilla  1 , Eugenia Lugo-Cervantes  2 , Cynthia Ordaz-Pichardo  3 , Jorge Luis Rosas-Trigueros  4 , María Eugenia Jaramillo-Flores  5
Affiliations

Apoptosis Induction of Agave lechuguilla Torrey Extract on Human Lung Adenocarcinoma Cells (SK-LU-1)

Luis Alberto Anguiano-Sevilla et al. Int J Mol Sci. .

Abstract

In this study, an ethanol extract of Agave lechuguilla was evaluated against six carcinogenic cell lines (HCT-15, MCF-7, PC-3, U-251, SK-LU-1 and K-562) with an inhibition of 75.7 ± 2.3% against the SK-LU-1 line. Based on the previous result, the extract was hydrolyzed and fractionated, to which the IC50 was determined; the cell line was more sensitive to the fractionated extract with an IC50 6.96 ± 0.15 µg/mL. Characterization by mass spectrometry showed the presence of kaempferol, quercetin and a flavonoid dimer formed by afzelechin-4β-8-quercetin, according to the generated fragmentation pattern. The fractionated extract presented cell death by apoptosis with 39.8% at 24 h. Molecular docking was performed with the molecules found to try to describe cell death by apoptosis through death receptors such as FasCD95, TNF-R1, DR4/5 and blocking signaling on the EGFR and K-Ras MAPK/ERK pathway, as well as through the intrinsic pathway activating tBID, which promotes the amplification of the apoptotic signal due to the activation of caspase-3, and consequently caspase-7. In addition to the activation of the IIb complex associated with cell death due to necroptosis.

Keywords: Agave lechuguilla; apoptosis; cytotoxic activity; mass spectrometry; molecular docking.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of flavonoids and biflavonoid dimer with numbers associated to in silico results. (a) Kaempferol 287 g/mol (b) Quercetin 302 g/mol, and (c) Biflavonoid (afzelequin 4β-8 quercetin), 574 g/mol.
Figure 1
Figure 1
Structure of flavonoids and biflavonoid dimer with numbers associated to in silico results. (a) Kaempferol 287 g/mol (b) Quercetin 302 g/mol, and (c) Biflavonoid (afzelequin 4β-8 quercetin), 574 g/mol.
Figure 2
Figure 2
Translocation of phosphatidylserine by flow cytometry (Annexin V-FITC/7-AAD staining). Representative plots of SK-LU-1 cells cultured in the presence fractioned extract of A. lechuguilla with an IC50 = 6.96 μg/mL, are shown (total apoptosis-time of exposure).
Figure 3
Figure 3
Binds of biflavonoid, kaempferol and quercetin with death receptor. The box indicates the binding region. (a) Biflavonoid binds to TNF-R1, (b) Biflavonoid binds to DR4, (c) Kaempferol binds to Fas/CD95, (d) Kaempferol binds to DR5 (e) Quercetin binds to TNF-R1, (f) Quercetin binds to DR4, (g) Biflavonoid binds to EGFR, and (h) Biflavonoid binds to K-Ras.
Figure 3
Figure 3
Binds of biflavonoid, kaempferol and quercetin with death receptor. The box indicates the binding region. (a) Biflavonoid binds to TNF-R1, (b) Biflavonoid binds to DR4, (c) Kaempferol binds to Fas/CD95, (d) Kaempferol binds to DR5 (e) Quercetin binds to TNF-R1, (f) Quercetin binds to DR4, (g) Biflavonoid binds to EGFR, and (h) Biflavonoid binds to K-Ras.
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