Human Oral Carcinoma KB Cells Research Articles

Beneficial efficacy of various propolis extracts and their digestive products by in vitro simulated gastrointestinal digestion

Propolis is a waxy substance from many plant material which is rich in polyphenols with numerous biological activities. The current experiment was designed to assess the antioxidant and cyclooxygenase-2 (COX-2) inhibitory activities of various propolis extracts and their digestive products on human oral carcinoma KB cells. Three different solvents like ethanol (EtOH), glycerol and water (before digestion; BD) as well as three different phases of in vitro simulated digestion (after digestion; AD) like oral (O), gastric (G) and gastrointestinal (GI) were used to mimic the human digestion model. Both phenolic and flavonoids contents, as well as antioxidant capacity, are significantly higher in EtOH extract than glycerol and water (BD). Whereas, the O phase of all solvent (AD) showed highest phenolic and flavonoids contents as well as antioxidant capacity than G or GI phase. Moreover, COX-2 protein expression was markedly downregulated on treatment with EtOH (BD) on oral carcinoma KB cells as compared to other extracts. Likewise, the addition of oral digested EtOH notably downregulated the COX-2 protein expression in oral carcinoma KB cells. In conclusion, the original (undigested) and oral digested propolis of EtOH showed perfect antioxidant and COX-2 inhibitory activity, owing to increased phenolic and flavonoids contents.

A new protoberberine alkaloid from Meconopsis simplicifolia (D. Don) Walpers with potent antimalarial activity against a multidrug resistant Plasmodium falciparum strain

Ethnopharmacological relevanceThe aerial components of Meconopsis simplicifolia (D. Don) Walpers are indicated in Bhutanese traditional medicine for treating malaria, coughs and colds, and the infections of the liver, lung and blood. This study is to validate the ethnopharmacological uses of this plant and also identify potent antimalarial drug leads through bioassays of its crude extracts and phytochemical constituents. Materials and methodsMeconopsis simplicifolia (D. Don) Walpers was collected from Bhutan and its crude MeOH extract was subjected to acid-base fractionation. Through repeated extractions, separations and spectroscopic analysis, the alkaloids obtained were identified and tested for their antimalarial and cytotoxicity activities. ResultsPhytochemical studies resulted in the isolation of one new protoberberine type alkaloid which we named as simplicifolianine and five known alkaloids: protopine, norsanguinarine, dihydrosanguinarine, 6-methoxydihydrosanguinarine and oxysanguinarine. Among the five of the alkaloids tested, simplicifolianine showed the most potent antiplasmodial activities against the Plasmodium falciparum strains, TM4/8.2 (chloroquine–antifolate sensitive strain) and K1CB1 (multidrug resistant strain) with IC50 values of 0.78μg/mL and 1.29μg/mL, respectively. The compounds tested did not show any significant cytotoxicity activities against human oral carcinoma KB cells and normal Vero cells of African kidney epithelial cells. ConclusionsThis study validated the traditional uses of the plant for the treatment of malaria and identified a new alkaloid, simplicifolianine as a potential antimalarial drug lead.

Systems biology approach for in vivo photodynamic therapy optimization of ruthenium-porphyrin compounds

Two arene ruthenium porphyrin compounds showing interesting photodynamic activity in vitro, [Ru(η6-p-PriC6H4Me)(PMP)Cl2] (PMP=5-(3-pyridyl)-10,15,20-triphenylporphyrin) and [Ru4(η6-p-PriC6H4Me)4(PTP)Cl8] (PTP=5,10,15,20-tetra(3-pyridyl)porphyrin) coined Rut1 and Rut4 respectively, have been evaluated in vivo. Porphyrins alone and the arene ruthenium porphyrin derivatives (Rut1 and Rut4) showed comparable spectroscopic and photophysical properties. The in vivo study consisted in selecting the optimal arene ruthenium porphyrin photosensitizer by using an original experimental design approach on mice bearing an ectopic human oral carcinoma xenograft. The model of experimental design demonstrated to be well suited to the empirical model-building of photodynamic therapy (PDT) response. Arene ruthenium porphyrins concentration and fluence level demonstrated no statistically significant influence on the tumor growth. On the contrary, the presence of ruthenium groups improved the in vivo photodynamic efficiency. By optical fiber fluorimetry, we demonstrated that both compounds exhibited enhanced accumulation in KB tumors from 24h to 96h post-intravenous injection. These experiments were completed by inductively coupled plasma mass spectrometry quantification of ruthenium in different organs including tumor tissue. Despite a statistically significant in vivo photodynamic efficiency for Rut4, cellular localization in human oral carcinoma KB cells using fluorescence microscopy demonstrated that both conjugates Rut1 and Rut4 accumulated only in cytoplasm of KB cells but not in the nucleus.

Design of Folate-Linked Liposomal Doxorubicin to its Antitumor Effect in Mice

Tumor cell targeting is a promising strategy for enhancing the therapeutic potential of chemotherapy agents. Polyethylene glycol (PEG)-coated (sterically stabilized) liposomes show enhanced accumulation on the surface of tumors, but steric hindrance by PEGylation reduces the association of the liposome-bound ligand with its receptor. To increase folate receptor (FR) targeting, we optimized the concentration and PEG spacer length of folate-PEG-lipid in liposomes. Three types of folate-linked liposomal doxorubicin were designed and prepared by optimizing the concentration and PEG spacer length of folate-PEG-lipid in PEGylated or non-PEGylated liposomes and by masking folate-linked liposomes where the folate ligand is "masked" by adjacent PEG spacers. The liposome targeting efficacy was evaluated in vitro and in vivo. In human oral carcinoma KB cells, which overexpress FR, modification with sufficiently long PEG spacer and a high concentration of folate ligand to non-PEGylated liposomes increased the FR-mediated association and cytotoxicity more than with PEGylated and masked folate-linked liposomes. On the contrary, in mice bearing murine lung carcinoma M109, modification with the folate ligand in PEGylated and masked folate-linked liposomes showed significantly higher antitumor effect than with non-PEGylated liposomes irrespective of the length of time in the circulation after intravenous injection. The results of this study will be beneficial for the design and preparation of ligand-targeting carriers for cancer treatment.

Properties of rhodium (II) complexes having cytostatic activity

Dimeric rhodium (II) carboxylate complexes [Rh 2(OOCR) 4L 2], [Rh 2(OOCR) 2(NN) 2L 2] 2+ and [Rh 2Cl 2(RCOO) 2(NN) 2] (R  PhCH(OH), MeCH(OH), HOOCCH(OH)CH(OH), Me; NN  2,2′-bipyridine, 1,10-phenanthroline) have been synthesized and characterized using electronic, NMR, and IR spectra. Cytostatic activity of these complexes has been tested for human oral carcinoma KB cell line. Some complexes with hydroxycarboxylates and [Rh 2(RCOO) 2(NN) 2] 2+ compounds show higher cytostatic activity than [Rh 2(OOCCH 3) 4(H 2O) 2].