1. Bufadienolide glycosides and bufadienolides from the whole plants of Helleborus lividus, and their cytotoxic activity
- Author
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Shingo Takano, Yoshihiro Mimaki, Naoya Tamura, Akihito Yokosuka, and Tomoki Iguchi
- Subjects
0106 biological sciences ,Stereochemistry ,ATPase ,Ranunculaceae ,HL-60 Cells ,Plant Science ,Bufadienolide ,Horticulture ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,medicine ,Humans ,Helleborus lividus ,Glycosides ,Na+/K+-ATPase ,Cytotoxicity ,Molecular Biology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Chemistry ,Glycoside ,General Medicine ,biology.organism_classification ,0104 chemical sciences ,Bufanolides ,Helleborus ,Mechanism of action ,biology.protein ,medicine.symptom ,010606 plant biology & botany - Abstract
Cytotoxicity-guided fractionation of the MeOH extract of Helleborus lividus Aiton ex Curtis (Ranunculaceae) resulted in the isolation of five undescribed bufadienolide glycosides and two undescribed bufadienolides, along with three known compounds. Their structures were determined by detailed spectroscopic analysis and hydrolysis studies. The isolated compounds showed cytotoxicity against HL-60 human leukemia cells and A549 human lung adenocarcinoma cells, with IC50 values ranging from 2.20 ± 0.01 nM to 0.77 ± 0.01 μM. The undescribed compound 3β-[(O-β- d -glucopyranosyl-(1 → 4)-α- l -rhamnopyranosyl)oxy]-14β,16β-dihydroxy-5β-bufa-20,22-dienolide induced apoptosis in HL-60 cells via a mitochondria-dependent apoptotic pathway. The average IC50 values of bufadienolide monorhamnosides for HL-60 and A549 cells were 10–20 times lower than those for Na+/K+ ATPase, implying that they induce tumor cell death via a mechanism of action other than Na+/K+ ATPase inhibition.
- Published
- 2020