Transformed Root Extract of Leonurus sibiricus Induces Apoptosis through Intrinsic and Extrinsic Pathways in Various Grades of Human Glioma Cells

Sitarek, Przemysław; Skała, Ewa; Toma, Monika; Wielanek, Marzena; Szemraj, Janusz; Skórski, Tomasz; Białas, Adam J.; Sakowicz, Tomasz; Kowalczyk, Tomasz; Radek, Maciej; Wysokińska, Halina; Śliwiński, Tomasz

doi:10.1007/s12253-016-0170-6

Cited by 32 publications

(31 citation statements)

References 36 publications

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“…Interestingly, administration of VA led to the restoration of levels of lipid peroxidation by-products and abnormalities in antioxidative status which were found to be altered after administration of DMBA alone [11].In cancer treatment; the potential anticancer effectiveness of whole plant or isolated plant extracts containing several natural compounds as well was tested. Interestingly, transformed root extract of Leonurus sibiricus is rich in various polyphenolic compounds including VA as well as gentisic acid,4hydroxybenzoic acid, 1,3-dicaffeoylquinic acid, and α-resorcylic acid, demonstrated an ability to inhibit proliferation and to induce apoptosis in glioma cells with these effects mediated via generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential, enhancement of S and G2/M cell cycle phases, and changes in mRNA levels of apoptotic factors including Bax, Bcl-2, p53, Caspase-3, -8 and -9 [12]. In HCT116 colorectal cancer cells, isolated VA inhibited angiogenesis…”

Section: Vanillic Acidmentioning

confidence: 99%

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

et al. 2020

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Globally, cancer is the second leading cause of death. Different conventional approaches to treat cancer include chemotherapy or radiotherapy. However, these are usually associated with various deleterious effects and numerous disadvantages in clinical practice. In addition, there are increasing concerns about drug resistance. In the continuous search for safer and more effective treatments, plant-derived natural compounds are of major interest. Plant phenolics are secondary metabolites that have gained importance as potential anti-cancer compounds. Phenolics display a great prospective as cytotoxic anti-cancer agents promoting apoptosis, reducing proliferation, and targeting various aspects of cancer (angiogenesis, growth and differentiation, and metastasis). Phenolic acids are a subclass of plant phenolics, furtherly divided into benzoic and cinnamic acids, that are associated with potent anticancer abilities in various in vitro and in vivo studies. Moreover, the therapeutic activities of phenolic acids are reinforced by their role as epigenetic regulators as well as supporters of adverse events or resistance associated with conventional anticancer therapy. Encapsulation of phyto-substances into nanocarrier systems is a challenging aspect concerning the efficiency of natural substances used in cancer treatment. A summary of phenolic acids and their effectiveness as well as phenolic-associated advances in cancer treatment will be discussed in this review.

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Section: Vanillic Acidmentioning

confidence: 99%

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

et al. 2020

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“…TR root extract triggered apoptosis on various grades (I-III) of human glioma cells by the generation of reactive oxygen species (ROS) in association with loss of mitochondrial membrane potential. TR also changed mRNA levels of Bax, Bcl-2, p53, Caspase-3, Caspase-8 and Caspase-9 involved in apoptosis suggesting its potential to stimulate both the intrinsic and extrinsic pathways of programmed cell death [40].…”

Section: /19mentioning

confidence: 95%

“…Leonurus sibiricus L. is a plant existing in southern Asia and Siberia which is widely used as a medicinal plant for anti-inflammatory, antibacterial, antioxidant, antiviral and anticancer effects [40]. Chromatographic analysis of TR extract demonstrated the presence of various phenolic compounds (GA, 4-hydroxybenzoic acid, vanilic acid, 1,3-dicaffeoylquinic acid, α-resorcylic acid).…”

Section: /19mentioning

confidence: 99%

Gentisic Acid, a Quinonoid Aspirin Metabolite in Cancer Prevention and Treatment. New Horizons in Management of Brain Tumors and Systemic Cancers

Altinöz¹,

Elmacı²,

Özpınar³

2018

J Cancer Res Oncobiol

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Gentisic Acid (GA) is an endogenously synthesized quinonoid phenolic acid in plants, where it functions as an immune molecule against viral plant pathogens via modifying microRNAs. In mammalians, GA is both consumed from exogenous sources (from fruits and vegetables) and produced endogenously as an endogenous siderophore and as a byproduct of tyrosine catabolism. Besides the edible plants, aspirin is also an important source of GA, since its catabolism produces GA. Noteworthy, humans with variant alleles of CYP2C9 which are incapable to produce GA during aspirin catabolism do not benefit from aspirin in reduction of adenomas in the large bowel. In past, GA was succesfully used in the treatment of rheumatological diseases in humans with high biosafety. GA has an affinity to connective tissue proteins and a higher retention of exogenous GA was demonstrated in humans with cancer. GA has both direct and indirect strong antioxidant effects as a free radical scavenger molecule and as an agonist of NRF2 (Nuclear factor erythroid-derived 2-like 2), an important transcription factor which regulates synthesis of antioxidant molecules. GA blocks cancer promotion in animal models in association with reduction of free radical products and stimulating antioxidant molecules. GA also exerts prominent antiinflammatory effects while stimulating elements of acquired immunity, lymphocytes; which likely occur due to its strong efficacies to block cyclooxygenases, 12-lipoxygenase and acting as a ligand of GPR35/CXCR8. GA also specifically inhibit protumorigenic signaling of Fibroblast Growth Factor (FGF) and cyclin dependent kinase-1 (CDK1). Sulfonated derivative of GA (2,5-dihydroxyphenylsulfonate, dobesilic acid) blocks subcutaneous growth of C6 glioma; and GA also acts as an agonist of Vasoactive Intestinal Polypeptide (VIP) pathway, which suppresses invasion of glioma cells in vitro. GA also inhibits OAT3/ SLC22A8, which involves efflux of chemotherapeutics from the brain which may help to achieve therapeutic concentrations of anticancer agents in brain tumors. In future, combined aspirin-GA preparates may be tested for potential activity in cancer prevention and treatment.

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“…Moreover, phytosterols demonstrate numerous health benefits, including lowering plasma cholesterol and triacylglyceride levels and reducing the risk of cardiovascular diseases (Quilez, Garcia-Lorda, & Salas-Salvado 2003). According to the literature, gentisic acid (as a phenolic acid, Figure 1c) has show chemopreventive effect against breast and brain cancers (Altinoz, Elmaci, Cengiz, Emekli-Alturfan, & Ozpinar 2018), while plant extracts rich in this active substance have exerted antiproliferative and apoptotic effect on glioma cell cultures (Sitarek et al 2017). However, phenolic acids are quite sensitive to light, high temperature, oxygen and the presence of different pH, enzymes and nutrients in the gastrointestinal tract (Munin & Edwards-Lévy 2011;Pasukamonset, Kwon, & Adisakwattana 2016).…”

Section: Introductionmentioning

confidence: 99%

‐sitosterol and gentisic acid loaded 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine liposomal particles

Jovanović¹,

Balanč²,

Ota³

et al. 2020

JEPM

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The aim of the present study was the examination of the impact of -sitosterol andgentisic acid on the characteristics of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine(DPPC) liposomal particles: (a) bilayer permeability (fluorescence spectroscopy),(b) particle size, polydispersity index (PDI) and zeta potential (photon correlationspectroscopy) and (c) thermal properties (differential scanning calorimetry). -sitosterol induced the increase of liposomal bilayer rigidity, due to rearranging ofthe phospholipid chains, while gentisic acid enhanced the membrane fluidity, dueto the reduced orderliness and the increase of phospholipid dynamics. The inclusionof -sitosterol in liposomes caused a significant increase in particle diameterand PDI, while the encapsulation of gentisic acid did not have influence on particlesize distribution. Apart from that, the presence of -sitosterol resulted in thesignificant zeta potential increase, and thus a better stability of liposomal spheres(in the absence and in the presence of gentisic acid). -sitosterol decreased maintransition temperature (Tm) and phase transition enthalpy (H), and caused thedisappearance of the pre-transition peak as well, whereas the presence of gentisicacid produced a slight decrease in Tm and increase of H. Therefore, gentisic acidhad more favourable, stabilizing interactions with phospholipids than -sitosterol.Thus, it can be concluded that -sitosterol is located in the bilayer interior betweenphospholipids acyl chains, and gentisic acid is incorporated near the outer leaflet ofthe phospholipid membrane, next to the polar head groups. -sitosterol and gentisicacid loaded DPPC liposomal particles have a potential to be used in food andpharmaceutical products, due to the important individual and possible synergisticbeneficial health properties of -sitosterol and gentisic acid.

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Transformed Root Extract of Leonurus sibiricus Induces Apoptosis through Intrinsic and Extrinsic Pathways in Various Grades of Human Glioma Cells

Cited by 32 publications

References 36 publications

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

Therapeutic Potential of Plant Phenolic Acids in the Treatment of Cancer

Gentisic Acid, a Quinonoid Aspirin Metabolite in Cancer Prevention and Treatment. New Horizons in Management of Brain Tumors and Systemic Cancers

‐sitosterol and gentisic acid loaded 1,2‐dipalmitoyl‐sn‐glycero‐3‐phosphocholine liposomal particles

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