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

Autor: DE Souza E Silva GW; Laboratório de Farmacologia Molecular, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil., Marques AM; Laboratório de Tecnologia para Biodiversidade em Saúde/LDFito, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil., Fontão APGA; Laboratório de Farmacologia Molecular, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil., DE Moura Lima SC; Instituto de Pesquisas de Produtos Naturais (IPPN), Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Kaplan MAC; Instituto de Pesquisas de Produtos Naturais (IPPN), Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil., Figueiredo MR; Laboratório de Tecnologia para Biodiversidade em Saúde/LDFito, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil., Sampaio ALF; Laboratório de Farmacologia Molecular, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil; andre.sampaio@fiocruz.br.
Jazyk: angličtina
Zdroj: Anticancer research [Anticancer Res] 2023 Mar; Vol. 43 (3), pp. 1245-1253.
DOI: 10.21873/anticanres.16271
Abstrakt: 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 IC 50 (1.17 μM) and for aurelianolide B, Jurkat was the most susceptible cell line (IC 50 2.25 μM). On the other hand, the multidrug resistant (MDR) cell line K562-Lucena 1 showed higher IC 50 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.
(Copyright © 2023 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
Databáze: MEDLINE
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