Gaillardin exerts potent antileukemic effects on HL‐60 cells and intensifies arsenic trioxide cytotoxicity: Providing new insight into sesquiterpene lactones in leukaemia treatment

The use of all‐trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard‐risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high‐risk subgroup more problematic, and possible side effects limit their cli...

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Published in:Clinical and experimental pharmacology & physiology 2024-04, Vol.51 (4), p.e13847-n/a
Main Authors: Noormohamadi, Hanieh, Hamzeloo‐Moghadam, Maryam, Bashash, Davood, Kargar, Maryam, Izadirad, Mehrdad, Hasanpour, Seyedeh Zahra, Gharehbaghian, Ahmad
Format: Article
Language:English
Subjects:
acute promyelocytic leukaemia
Anticancer properties
Apoptosis
Arsenic
Arsenic trioxide
Cell cycle
Cytotoxicity
Flow cytometry
Gaillardin
Gene expression
Inula oculus‐christi
Lactones
Leukemia
Metabolites
Patients
Reactive oxygen species
Retinoic acid
Risk
Risk groups
Sesquiterpene lactones
Side effects
Subgroups
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Summary:The use of all‐trans retinoic acid and arsenic trioxide resulted in favourable therapeutic responses in standard‐risk acute promyelocytic leukaemia (APL) patients. However, resistance to these agents has made treating the high‐risk subgroup more problematic, and possible side effects limit their clinical dosages. Numerous studies have proven the cytotoxic properties of Gaillardin, one of the Inula oculus‐christi‐derived sesquiterpene lactones. Due to the adverse effects of arsenic trioxide on the high‐risk subgroup of APL patients, we aimed to assess the cytotoxic effect of Gaillardin on HL‐60 cells as a single or combined‐form approach. The results of the trypan blue and MTT assays outlined the potent cytotoxic properties of Gaillardin. The flow cytometric analysis and the mRNA expression levels revealed that Gaillardin attenuated the proliferative capacity of HL‐60 cells through cell cycle arrest and induced apoptosis via reactive oxygen species generation. Moreover, the results of synergistic experiments indicated that this sesquiterpene lactone sensitizes HL‐60 cells to the cytotoxic effects of arsenic trioxide. Taken together, the findings of the present investigation highlighted the antileukemic characteristics of Gaillardin by inducing G1 cell cycle arrest and triggering apoptosis. Gaillardin acts as an antileukemic metabolite against HL‐60 cells and this study provides new insight into treating APL patients, especially in the high‐risk subgroup.
ISSN:0305-1870
1440-1681
DOI:10.1111/1440-1681.13847