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Planta Med 2022; 88(06): 429-439
DOI: 10.1055/a-1395-9046
Biological and Pharmacological Activity
Original Papers

A Withanolide-rich Fraction of Athenaea velutina Induces Apoptosis and Cell Cycle Arrest in Melanoma B16F10 Cells

Alisson A. Almeida 
1   Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Brazil
,
Graziela D. A. Lima
2   Departamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
,
Marinês Eiterer
3   Independent Researcher
,
Laís A. Rodrigues
1   Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Brazil
,
Juliana A. A. do Vale
2   Departamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
,
Ana C. Zanatta 
4   Universidade Estadual Paulista (Unesp), Instituto de Química, Araraquara, São Paulo, Brazil
,
Gustavo C. Bressan
1   Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Brazil
,
Leandro L. de Oliveira
2   Departamento de Biologia Geral, Universidade Federal de Viçosa, Viçosa, Minas Gerais, Brazil
,
João P. V. Leite
1   Departamento de Bioquímica e Biologia Molecular, Universidade Federal de Viçosa, Viçosa, Brazil
› Author Affiliations
Supported by: Fundação de Amparo à Pesquisa do Estado de Minas Gerais CDS - APQ-02540-15 Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico 431330/2018-2 Supported by: Conselho Nacional de Desenvolvimento Científico e Tecnológico GD - 42313/2015-7
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Abstract

Athenaea velutina is a promising Brazilian shrub with cytotoxic and antimigratory properties against cancer cells. However, the mechanism of induction of cancer cell death and the compounds involved remain unknown. To ascertain these bioactive compounds, bioassay-guided fractionation was performed, alongside the appropriate in vitro tests. A withanolide-rich fraction (FAv_5) from the dichloromethane extract increased cytotoxic activity by 1.5-fold (IC50 = 2.1 µg/mL). Fourteen withanolide steroids were tentatively identified for the first time for this species by mass spectrometry coupled to liquid chromatography (LC MS/MS), including withanolide A, aurelianolide A, and aurelianolide B. FAv_5 significantly decreased cell proliferation, migration, and invasion with a selectivity index greater than 8 for B16F10 cells. Furthermore, flow cytometry with annexin V fluorescein isothiocyanate/propidium iodide (V-FITC/PI) staining showed FAv_5 to promote cell cycle arrest at the G0/G1-phase as well as apoptotic cell death. Overall, these findings highlight A. velutina as a source of withanolide-steroids that inhibit cancer cell proliferation through apoptosis and cell cycle blockade mechanisms. Details on the geographic distribution of A. velutina and species conservation strategies have also been highlighted.

Key words

Athenaea velutina - Solanaceae - withanolides - apoptosis - cell cycle arrest - geographic distribution

Supporting Information

    Second-order mass spectra of the precursor ion at m/z 531 (1) (Fig. S1), m/z 471 (2) (Fig. S2), m/z 573 (3) (Fig. S3), m/z 513 (4) (Fig. S4), m/z 529 (5) (Fig. S5), m/z 545 (6) (Fig. S6), m/z 497 (7) (Fig. S7), m/z 559 (8) (Fig. S8), m/z 511 (9) (Fig. S9), m/z 497 (10) (Fig. S10), m/z 571 (11) (Fig. S11), m/z 555 (12) (Fig. S12), m/z 479 (13) (Fig. S13), m/z 495 (14) (Fig. S14), the proposed fragmentation pattern of the precursor ion at m/z 497 (10), with different pathways for the formation of the main product ions (Fig. S15), A. velutina morphology, distribution areas, and conservation in Brazil (Fig. S16) are included as Supporting Information.

  • Supporting Information


Publication History

Received: 03 October 2020

Accepted after revision: 19 February 2021

Article published online:
14 April 2021

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