The anti-leukemic activity of a luteolin-apigenin enriched fraction from an edible and ethnomedicinal plant, Elsholtzia stachyodes, is exerted through an ER stress/autophagy/cell cycle arrest/ apoptotic cell death signaling axis - 26/02/23
, Pitchaya Mungkornasawakul e, Kongkiat Trisuwan e, Jiraprapa Wipasa f, Angkana Inta b, Duncan R. Smith g, Pathrapol Lithanatudom b, c, ⁎, 1 Abstract |
Background |
Elsholtzia is a genus in the family Lamiaceae, and some species in this genus are commonly used for food and in ethnomedicinal formulations by some ethnic groups of China and Thailand. Despite their apparent utility, few studies have been conducted to evaluate their potential as sources of medicinally active agents.
Purpose |
We aimed to investigate the cytotoxicity of ethanolic extracts from three selected edible plant species of the genus Elsholtzia and the most promising extract was further characterized for the bioactive constituents and signaling mechanisms associated with the anti-leukemic activity.
Materials and methods |
Ethanolic extracts were screened for cytotoxicity using flow cytometry. HPLC and LC-MS were used to analyze the chemical constituents of the most potent fraction from E. stachyodes. The relevant mechanism of action was assessed by western blot and multispectral imaging flow cytometry (MIFC).
Results |
The most potent anti-leukemic activity was observed with the ethanolic extract from E. stachyodes. Luteolin and apigenin were characterized as the major constituents in the fraction from E. stachyodes. Mechanistically, the luteolin-apigenin enriched fraction (LAEF) induced the UPR, increased autophagic flux, induced cell cycle arrest and apoptotic cell death. LAEF showed significantly less cytotoxicity towards peripheral blood mononuclear cells (PBMCs) as compared to leukemia cell lines.
Conclusion |
This study is the first to report E. stachyodes as a new source of luteolin and apigenin which are capable of triggering leukemic cell death. This could lead to a novel strategy against leukemia using ethnomedicinal plant extracts as an alternative or supplemental anti-cancer agent.
Le texte complet de cet article est disponible en PDF.Graphical Abstract |
Highlights |
• | The genus Elsholtzia is commonly used for food and ethnomedicine by some northern Thai ethnic groups. |
• | The ethanolic extract from Elsholtzia stachyodes showed the most potent anti-leukemic against three human leukemia cell lines. |
• | Luteolin and apigenin were the major compounds found in the most potent anti-leukemic subfraction from the ethanolic extract of E. stachyodes. |
• | Luteolin-Apigenin Enriched Fraction (LAEF) induced the UPR, autophagic flux, cell cycle arrest and apoptosis in U937. |
• | LEAF exhibited less cytotoxicity towards healthy peripheral blood mononuclear cells (PBMCs) as compared to U937 cells. |
Abbreviations : Akt, ATF-6, ATG5, ATP, CHOP, CML, c-Myc, DR5, EC, EG, ER, ERdj, ES, Fas/FasL, FADD, GRP78, Hsp90, LAEF, LAMP-1, LC3, MIFC, PARP, PBMCs, ROS, STAT3, UPR, XBP-1, XBP-1sp
Keywords : Elsholtzia, Luteolin, Apigenin, Anti-leukemic signaling, Multispectral imaging flow cytometry
Plan
Vol 160
Article 114375- avril 2023 Retour au numéro
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