Modulatory Impact of Lamiaceae Metabolites on Apoptosis of Human Leukemia Cells

Abstract

Lamiaceae species are rich sources of biologically active compounds which have been applied in medicine since ancient times. Especially their antineoplastic properties have been thoroughly studied with respect to their putative application in chemoprevention and adjuvant therapy of cancer. However, the most known biological effects of Lamiaceae have been ascribed to their essential oil fractions, whereas their (poly)phenolic metabolites being also abundant in these plants, are much less recognized, nevertheless contributing to their beneficial properties, such as anti-cancer actions. The aim of this study was to evaluate the impact of dried aqueous extracts from common thyme (Thymus vulgaris L.) (ExTv), wild thyme (Thymus serpyllum L.) (ExTs), sweet marjoram (Origanum majorana L.) (ExOm), and peppermint (Mentha × piperita L.) (ExMp), as well as (poly)phenolic compounds: caffeic acid (CA), rosmarinic acid (RA), lithospermic acid (LA), luteolin-7-O-β-glucuronide (Lgr), luteolin-7-O-rutinoside (Lr), eriodictyol-7-O-rutinoside (Er), and arbutin (Ab), on unstimulated Jurkat cells, in comparison with their effect on staurosporine-stimulated Jurkat cells. Jurkat T cells were incubated with different concentrations of ExTv, ExTs, ExOm, ExMp, Lgr, LA, Er, Lr, RA, CA, or Ab. Subsequently, staurosporine was added to half of the samples and flow cytometry combined with fluorescence-activated cell sorting analysis was conducted, which allowed for the selection of early and late apoptotic cells. Both ExTs and ExOm stimulated apoptosis of Jurkat cells and enhanced the proapoptotic effect of staurosporine. Conversely, ExTv and ExMp demonstrated no clear effect on apoptosis. CA and RA raised the staurosporine-induced apoptotic effect. The impact of Er and Lgr on Jurkat cells showed fluctuations depending on the compound concentration. Neither Er nor Ab altered staurosporine-induced apoptosis in Jurkat cells, whereas Lgr seemed to weaken the proapoptotic action of staurosporine. The most evident observation in this study was the pro-apoptotic action of ExTs and ExOm observed both in staurosporine-unstimulated and stimulated Jurkat cells. Additionally, an enhancement of staurosporine-induced apoptosis by caffeic and rosmarinic acids was reported. Therefore, it might be concluded that these are the mixtures of biologically active polyphenols which often exert more pronounced beneficial effects than purified molecules.

Wild thyme (Thymus serpyllum L.): a review of the current evidence of nutritional and preventive health benefits*

“…Fumigant activity against food crop pests ( 148 ) and houseflies ( 49 ) is well established. In vitro , the cytotoxicity of extracts (e.g., containing rosmarinic and lithospermic acid) in cancer cell lines ( 149 ), particularly in human breast cancer ( 119 ), and human leukemia cells ( 120 ) has been investigated. Different cytotoxic modes of action of polyphenols in extracts and pure phenols (thymol, carvacrol) on different cancer cell lines are known; normal and healthy cells seem to be not negatively affected less or not negatively impacted ( 3 ).…”

“…The aqueous and methanolic extract of T. serpyllum were tested for a number of different pharmacological activities, e.g., chemopreventive activities and as an adjunct therapy for the cancer (119)(120)(121). Aqueous tea infusions and essential oils has shown to ameliorate the oxidation susceptibility of low-density lipoproteins (LDL) in a dose-dependent manner as found in a copper-induced LDL oxidation in-vitro model (122), antithrombin activity (123), antidiabetic/alpha-glucosidase inhibition activity (124, 125), liver and hepatoprotective activity (126) and anticholinesterase activity (127).…”

Mentha piperita: Essential Oil and Extracts, Their Biological Activities, and Perspectives on the Development of New Medicinal and Cosmetic Products

“…The essential oil exhibited strong antimicrobial activity and moderate antioxidant activity, but a low cytotoxic effect in HCT 116 cells (colorectal cancer), while the cytotoxic activity on non-cancerous cell line HaCaT was not significant [50]. In one more study, the aqueous extract of M. piperita did not have a clear effect on the apoptosis of human leukemia cells [111]. The peppermint oil was inactive against BEL-7402 cell [19].…”

“…Searching for alternative and complementary medical products from plants is a topical issue for the treatment of cancer. Therefore, there are many studies directed at the study of different plant resources in the search for anticancer active substances or active substances for cancer prevention [19,50,78,81,[108][109][110][111][112][113][114].…”