title: Cooperative antiproliferative and differentiation-enhancing activity of medicinal plant extracts in acute myeloid leukemia cells.
abstract: Acute myeloid leukemia (AML) is an aggressive hematopoietic malignancy with poor prognosis and limited treatment options. Sea buckthorn (Hippophae rhamnoides) berries, dog rose (Rosa canina) rosehips, and garden sage (Salvia officinalis) and oregano (Origanum vulgare) aerial parts are widely used in traditional medicine and exhibit antitumor effects in preclinical models. However, these plants remain scarcely tested for antileukemic activity. Here, we show that their water-ethanol leaf extracts reduced the growth and viability of AML cells and, at non-cytotoxic doses, potentiated cell differentiation induced by a low concentration of 1α,25-dihydroxyvitamin D3, the hormonal form of vitamin D, in a cell type-dependent manner. The latter effect was accompanied by upregulation of the vitamin D receptor protein components and its transcriptional activity. Furthermore, at minimally effective doses the extracts cooperated with one another to produce marked cytostatic effects associated with a partial S-phase arrest and a modest induction of apoptosis. In contrast, these combinations only slightly affected the growth and viability of proliferating normal human peripheral blood mononuclear cells. In addition, the extracts strongly inhibited microsomal lipid peroxidation and protected normal erythrocytes against hypoosmotic shock. Our results suggest that further exploration of the enhanced antileukemic effects of the combinations tested here may lead to the development of alternative therapeutic and preventive approaches against AML.
authors.affiliation: Department of Biophysics and Biomedicine, Al-Farabi Kazakh National University, Almaty 480078, Kazakhstan.
authors.forename: Gulzhan T
authors.initials: GT
authors.lastname: Zhamanbayeva
authors.affiliation: Laboratory of Membrane Physiology, Institute of Human and Animal Physiology, Almaty 050060, Kazakhstan.
authors.forename: Araylim N
authors.initials: AN
authors.lastname: Aralbayeva
authors.affiliation: Laboratory of Membrane Physiology, Institute of Human and Animal Physiology, Almaty 050060, Kazakhstan.
authors.forename: Maira K
authors.initials: MK
authors.lastname: Murzakhmetova
authors.affiliation: Department of Biophysics and Biomedicine, Al-Farabi Kazakh National University, Almaty 480078, Kazakhstan.
authors.forename: Sultan T
authors.initials: ST
authors.lastname: Tuleukhanov
authors.affiliation: Department of Clinical Biochemistry and Pharmacology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel. Electronic address: misha@bgu.ac.il.
authors.forename: Michael
authors.initials: M
authors.lastname: Danilenko
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use; D018922:HL-60 Cells; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D009997:Osmotic Pressure; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry*; D059808:Polyphenols / Q000494:pharmacology / Q000627:therapeutic use; D017208:Rats, Wistar; D018167:Receptors, Calcitriol / Q000378:metabolism; D020298:U937 Cells
chemical_list: D005419:Flavonoids; D010936:Plant Extracts; D059808:Polyphenols; D018167:Receptors, Calcitriol; D002117:Calcitriol
keywords: Acute myeloid leukemia; Cell cycle; Cell differentiation; Cell proliferation; Medicinal plant extracts; Vitamin D