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Research ArticleExperimental Studies

Aurelianolides from Aureliana fasciculata var. fasciculata Trigger Apoptosis With Caspase Activation in Human Leukemia Cells

GUSTAVO WERNECK DE SOUZA E SILVA, ANDRÉ MESQUITA MARQUES, ANA PAULA GREGÓRIO ALVES FONTÃO, SIMONE CRISTINA DE MOURA LIMA, MARIA AUXILIADORA COELHO KAPLAN, MARIA RAQUEL FIGUEIREDO and ANDRÉ LUIZ FRANCO SAMPAIO
Anticancer Research March 2023, 43 (3) 1245-1253; DOI: https://doi.org/10.21873/anticanres.16271
GUSTAVO WERNECK DE SOUZA E SILVA
1Laboratório de Farmacologia Molecular, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil;
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ANDRÉ MESQUITA MARQUES
2Laboratório de Tecnologia para Biodiversidade em Saúde/LDFito, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil;
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ANA PAULA GREGÓRIO ALVES FONTÃO
1Laboratório de Farmacologia Molecular, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil;
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SIMONE CRISTINA DE MOURA LIMA
3Instituto de Pesquisas de Produtos Naturais (IPPN), Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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MARIA AUXILIADORA COELHO KAPLAN
3Instituto de Pesquisas de Produtos Naturais (IPPN), Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil
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MARIA RAQUEL FIGUEIREDO
2Laboratório de Tecnologia para Biodiversidade em Saúde/LDFito, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil;
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ANDRÉ LUIZ FRANCO SAMPAIO
1Laboratório de Farmacologia Molecular, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil;
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  • For correspondence: andre.sampaio@fiocruz.br
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Abstract

Background/Aim: Aurelianolide A and B were identified and isolated from Aureliana fasciculata var. fasciculata leaves. Withanolides are naturally occurring C-28 steroidal lactone triterpenoids with cytotoxic and anticancer properties, among other relevant pharmacological activities. Herein we have described, for the first time, the cytotoxic effects of aurelianolides on human cancer cells. Materials and Methods: Aurelianolide A and B were tested on human leukemia cell lines: THP-1, MOLT-4, Jurkat, K562 and K562-Lucena 1. Results: For aurelianolide A, MOLT-4 had the lower IC50 (1.17 μM) and for aurelianolide B, Jurkat was the most susceptible cell line (IC50 2.25 μM). On the other hand, the multidrug resistant (MDR) cell line K562-Lucena 1 showed higher IC50 for both aurelianolides. Using 293T, a non-tumor embryonic kidney cell line, we observed an excellent selectivity index for both aurelianolides, from 2.24 (aurelianolide B in K562-Lucena 1) to 45.5 (aurelianolide A in MOLT-4). Aurelianolide A and B activated caspase 3/7 with consequent induction of apoptosis on Jurkat and K562-Lucena 1 cell lines. We have not observed induction of necrosis. Conclusion: Aurelianolides A and B have important cytotoxic effects on human leukemia cell lines by the activation of the caspase pathway.

Key Words:
  • Leukemia
  • apoptosis
  • Solanaceae
  • Aureliana fasciculata
  • var. fasciculata
  • withanolides
  • aurelianolides
  • Received November 16, 2022.
  • Revision received December 8, 2022.
  • Accepted December 9, 2022.
  • Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 43 (3)
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Aurelianolides from Aureliana fasciculata var. fasciculata Trigger Apoptosis With Caspase Activation in Human Leukemia Cells
GUSTAVO WERNECK DE SOUZA E SILVA, ANDRÉ MESQUITA MARQUES, ANA PAULA GREGÓRIO ALVES FONTÃO, SIMONE CRISTINA DE MOURA LIMA, MARIA AUXILIADORA COELHO KAPLAN, MARIA RAQUEL FIGUEIREDO, ANDRÉ LUIZ FRANCO SAMPAIO
Anticancer Research Mar 2023, 43 (3) 1245-1253; DOI: 10.21873/anticanres.16271

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Aurelianolides from Aureliana fasciculata var. fasciculata Trigger Apoptosis With Caspase Activation in Human Leukemia Cells
GUSTAVO WERNECK DE SOUZA E SILVA, ANDRÉ MESQUITA MARQUES, ANA PAULA GREGÓRIO ALVES FONTÃO, SIMONE CRISTINA DE MOURA LIMA, MARIA AUXILIADORA COELHO KAPLAN, MARIA RAQUEL FIGUEIREDO, ANDRÉ LUIZ FRANCO SAMPAIO
Anticancer Research Mar 2023, 43 (3) 1245-1253; DOI: 10.21873/anticanres.16271
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Keywords

  • Leukemia
  • apoptosis
  • Solanaceae
  • Aureliana fasciculata
  • var. fasciculata
  • withanolides
  • aurelianolides
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