Human Oral Cancer KB Research Articles

Baicalein inhibits KB oral cancer cells by inducing apoptosis via modulation of ROS

The theme of the current examination was to evaluate the anticancer activity of baicalein (5,6,7-trihydroxyflavone) in human oral cancer KB-cells by observing cell restraint intercellular ROS movement and apoptotic changes using 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay and 2,7-dichlorodihydrofluorescein diacetate (DCFH-DA) test. The concentration of baicalein at 80 μM caused 100% cancer cell inhibition. Therefore, lower concentrations i.e. 10, 20 and 40 μM were selected in the present study. Baicalein at 40 μM significantly hindered human oral cancer KB cells. In the interim, incendiary and apoptosis were seen through expanded ROS action that actuated apoptotic cell death. The results of the present study suggested that the anticancer effect of baicalein is likely due to its potential to improve ROS level and hence the increased apoptotic activity. This study suggested that baicalein might be a potential candidate for the treatment of oral cancer.

Synthesis of folate modified chitosan-based nanomicelles and its in vitro anti-tumor activity

To design and synthesize folate-modified pH-responsive chitosan-based nanomicelles and investigate the in vitro anti-tumor activity of the drug-loaded micelles. CHI-DMA was obtained by reductive amination reaction of aldehyde-based chitosan and hydrophilic amine compounds, and CHI-DMA-LA was obtained by condensation reaction with lauric acid; FA-CHI-DMA-LA was obtained after modification with folic acid (FA). The drug-loaded nanomicelles FA-CHI-DMA-LA/DOX were assembled by solvent change method. The physicochemical properties of polymers were characterized by hydrogen nuclear magnetic resonance and transmission electron microscope. The particle size and surface potential were determined by dynamic light scattering method. Folic acid access rate, doxorubicin (DOX) loading rate and entrapped efficiency were measured by UV-vis spectrophotometer. The drug release properties of DOX-loaded micelles in vitro were monitored by fluorescence spectrophotometer at different pHs (7.4, 6.5, 5.0). The cytotoxicity against human oral cancer KB cells was detected by MTT assay. Fluorescence microscope and flow cytometry were applied to investigate the phagocytosis of DOX-loaded micelles on KB cells. FA-CHI-DMA-LA was synthesized. The particle sizes of FA-CHI-DMA-LA-1 and FA-CHI-DMA-LA-2 micelles which used for the subsequent experiments were (73±14) nm and (106±15) nm, zeta potential were (15.59±1.98) mV and (21.20±2.35) mV, respectively. The drug loading rates of drug-loaded micelles FA-CHI-DMA-LA-1/DOX and FA-CHI-DMA-LA-2/DOX are (4.08±1.12)%and (4.12±0.44)%, respectively. In vitro drug release is pH-responsive, with cumulative release of DOX up to 37%and 36%at pH 5.0, which is about 1.5 times higher than that of pH 7.4. For FA-CHI-DMA-LA micelles with 1.25 to 125 μg/mL concentration, the survival rate of KB cells is more than 70%after incubation for 24 hours. The cell uptake of FA-CHI-DMA-LA/DOX micelles was enhanced compared to CHI-DMA-LA/DOX, and the cell uptake was higher in incubation without FA medium than that with FA. Compared with free DOX or CHI-DMA-LA/DOX, FA-CHI-DMA-LA/DOX nanomicelles showed higher cyctoxicity to KB cells, especially the FA-CHI-DMA-LA-2/DOX nanomicelles, the cell survival rate was about 17% after incubation for 24 hours. FA-modified chitosan-based nanomicelle with good biocompatibility was successfully prepared, which exhibits tumor microenvironmental pH responsive drug release and tumor targeting.

Retracted: Tanshinone IIA Induces Apoptosis in Human Oral Cancer KB Cells through a Mitochondria-Dependent Pathway.

[This retracts the article DOI: 10.1155/2014/540516.].

Synthesis, cytotoxicity against human oral cancer KB cells and structure–activity relationship studies of trienone analogues of curcuminoids

A general method for the synthesis of substituted (1E,4E,6E)-1,7-diphenylhepta-1,4,6-trien-3-ones, based on the aldol condensations of substituted 4-phenylbut-3-en-2-ones and substituted 3-phenylacrylaldehydes, was achieved. The natural trienones 4 and 5 have been synthesized by this method, together with the trienone analogues 9–20. These analogues were evaluated for their cytotoxic activity against human oral cancer KB cell line. The structure–activity relationship study has indicated that the analogues with the 1,4,6-trien-3-one function are more potent than the curcuminoid-type function. Analogues with meta-oxygen function on the aromatic rings are more potent than those in the ortho- and para-positions. Free phenolic hydroxy group is more potent than the corresponding methyl ether analogues. Among the potent trienones, compounds 11, 18 and 20 were more active than the anticancer drug ellipticine. All compounds were also evaluated against the non-cancerous Vero cells and it was found that compounds 11, 12 and 17 were much less toxic than curcumin (1); they showed high selectivity indices of 35.46, 33.46 and 31.68, respectively. These analogues are regarded as the potent trienones for anti-oral cancer study.

Tanshinone IIA induces apoptosis in human oral cancer KB cells through a mitochondria-dependent pathway.

Tanshinone IIA (Tan IIA), an active phytochemical in the dried root of Salvia miltiorrhiza Bunge, has shown an antiproliferative activity on various human cancer cell lines including nasopharyngeal carcinoma cells. However, the effects of Tan IIA on human oral cancer cells are still unknown. This study aimed to investigate the antiproliferative effects of Tan IIA on human oral cancer KB cells and explored the possible underlying mechanism. Treatment of KB cells with Tan IIA suppressed cell proliferation/viability and induced cell death in a dose-dependent manner through sulforhodamine B colorimetric assay. Observation of cell morphology revealed the involvement of apoptosis in the Tan IIA-induced growth inhibition on KB cells. Cell cycle analysis showed a cell cycle arrest in G2/M phase on Tan IIA-treated cells. The dissipation of mitochondrial membrane potential observed by flow cytometry and the expression of activated caspases with the cleaved poly (ADP-ribose) polymerase under immunoblotting analysis indicated that Tan IIA-induced apoptosis in KB cells was mediated through the mitochondria-dependent caspase pathway. These observations suggested that Tan IIA could be a potential anticancer agent for oral cancer.

The anti-proliferation and anti-migration dual effects of aloe-emodin on KB cells and its mechanism

To investigate the anti-proliferation and anti-migration dual effects of aloe-emodin on KB cells and its mechanisms. KB cells were treated with 2.5, 5, 10, 20 and 40 micromol/L aloe-emodin. Crystal violet assay was used to determine the long-term growth inhibition of aloe-emodin on human oral cancer KB cells. Scratch wound-healing motility assay was used to measure the antimigration effect The protein kinase C alpha and c-myc expression changes in protein levels were detected by Western blotting. A durable cell growth inhibitory effect of aloe-emodin on KB cells was found. Treatment of aloe-emodin resulted in the inhibition of cell migration. The protein kinase C alpha and c-myc in protein levels were decreased upon treatment with aloe-emodin compared with controls. The anti-proliferation and anti-migration effects of aloe-emodin on KB cells are associated with the suppression of protein kinase C pathway.

A novel peroxisome proliferator-activated receptor α/γ agonist, BPR1H0101, inhibits topoisomerase II catalytic activity in human cancer cells

Peroxisome proliferator-activated receptor (PPAR) gamma agonists are used clinically for treating diabetes mellitus and cancer. 2-Methyl-2[(1-{3-phenyl-7-propylbenzol[d]isoxazol-6-yl}oxy)propyl]-1H-4-indolyl) oxy]propanoic acid (BPR1H0101) is a novel synthetic indole-based compound, discovered through research to identify new PPARgamma agonists, and it acts as a dual agonist for PPARgamma and PPARalpha. Isobologram analysis demonstrated that BPR1H0101 is capable of antagonistic interaction with the topoisomerase (topo) II poison, VP16. A study of its mechanism showed that BPR1H0101 could inhibit the catalytic activity of topo II in vitro, but did not produce detectable topo II-mediated DNA strand breaks in human oral cancer KB cells. Furthermore, BPR1H0101 could inhibit VP16-induced topo II-mediated DNA cleavage and ataxia-telangiectasia-mutated phosphorylation in KB cells. The results suggest that BPR1H0101 can interfere with the topo II reaction by inhibiting catalytic activity before the formation of the intermediate cleavable complex; consequently, it can impede VP16-induced topo II-mediated DNA cleavage and cell death. This is the first identified PPARalpha/gamma agonist that can serve as a topo II catalytic inhibitor, to interfere with VP16-induced cell death. The result might have relevance to the clinical use of the PPARalpha/gamma agonist in combination chemotherapy.

Aloe-emodin induces in vitro G2/M arrest and alkaline phosphatase activation in human oral cancer KB cells

Aloe-emodin is a natural anthraquinone compound from the root and rhizome of Rheum palmatum. In this study, KB cells were treated with 2.5, 5, 10, 20, and 40 microM aloe-emodin for 1 to 5 days. The results showed that aloe-emodin inhibited cancer cells in a dose-dependent manner. Treatment with aloe-emodin at 10 to 40 microM resulted in cell cycle arrest at G2/M phase. The alkaline phosphatase (ALP) activity in KB cells increased upon treatment with aloe-emodin when compared to controls. This is one of the first studies to focus on the expression of ALP in human oral carcinomas cells treated with aloe-emodin. These results indicate that aloe-emodin has anti-cancer effect on oral cancer, which may lead to its use in chemotherapy and chemopreventment of oral cancer.

Inhibition of growth and increase of alkaline phosphatase activity in cultured human oral cancer cells by all- trans retinoic acid

In this study, the effects of all- trans retinoic acid (ATRA) on human oral cancer cells with regard to cell growth, the cell cycle, and alkaline phosphatase (ALP) activity were evaluated. Human oral cancer KB cells were treated with various concentrations of ATRA, and cell growth was then determined using the MTT viability assay. The cell-cycle distribution and ALP activity were analysed using a flow cytometer and chemical analyser, respectively. The KB cells were inhibited by ATRA at concentrations of 1–16 μM (1 μM, P < 0.05; 2 μM, P < 0.01; 4, 8 and 16 μM, P < 0.001) in a dose-dependent manner. ATRA arrested KB cells in the G0/G1 phase. The ALP activity in KB cells was increased by ATRA. This is one of the first studies to focus on the expression of ALP in human head-and-neck carcinoma cells treated with retinoids. These findings suggest that the anti-tumour effects of ATRA on human oral cancer are associated with G0/G1 phase arrest and an increase in ALP activity.

Synthesis and evaluation of novel pyrimido-acridone, -phenoxadine, and -carbazole as topoisomerase II inhibitors.

As part of a series of studies to discover new topoisomerase II inhibitors, novel pyrimidoacridones, pyrimidophenoxadines, and pyrimidocarbazoles were synthesized, and in vitro and in vivo antitumor activities and DNA-protein and/or DNA-topoisomerase II cross-linking activity as an indicator of topoisomerase II-DNA cleavable complex formation were evaluated. The pyrimidocarbazoles possessed high in vitro and in vivo potencies. Compound 26 (ER-37326), 8-acetyl-2-[2-(dimethylamino)ethyl]-1H-pyrimido[5,6,1-jk]carbazole-1,3(2H)-dione, showed in vitro growth inhibitory activity with respective IC(50) values of 0.049 microM and 0.35 microM against mouse leukemia P388 and human oral cancer KB. In vivo, this compound inhibited the tumor growth of mouse sarcoma M5076 implanted into mice with T/C values of 42% and 13% at 3.13 and 6.25 mg/kg/d respectively without significantly affecting the body weight. In addition, compound 26 (ER-37326) increased the formation of DNA-topoisomerase II cross-linking in P388 cells.

Receptor-targeted gene delivery via folate-conjugated polyethylenimine.

A novel synthetic gene transfer vector was evaluated for tumor cell-specific targeted gene delivery. The folate receptor is a tumor marker overexpressed in more than 90% of ovarian carcinomas and large percentages of other human tumors. Folic acid is a high affinity ligand for the folate receptor that retains its binding affinity upon derivatization via its gamma carboxyl. Folate conjugation, therefore, presents a potential strategy for tumor-selective targeted gene delivery. In the current study, we investigated a series of folate conjugates of the cationic polymer polyethylenimine (PEI) for potential use in gene delivery. A plasmid containing a luciferase reporter gene (pCMV-Luc) and the folate receptor expressing human oral cancer KB cells were used to monitor gene transfer efficiency in vitro. Transfection activity of polyplexes containing unmodified polyethylenimine was highly dependent on the positive to negative charge (or the N/P) ratio. Folate directly attached to PEI did not significantly alter the transfection activity of its DNA complexes compared to unmodified PEI. Modification of PEI by polyethyleneglycol (PEG) led to a partial inhibition of gene delivery compared to unmodified PEI. Attaching folates to the distal termini of PEG-modified PEI greatly enhanced the transfection activity of the corresponding DNA complexes over the polyplexes containing PEG-modified PEI. The enhancements were observed at all N/P ratios tested and could be blocked partially by co-incubation with 200 microM free folic acid, which suggested the involvement of folate receptor in gene transfer. Targeted vectors based on the folate-PEG-PEI conjugate are potentially useful as simple tumor-specific vehicles of therapeutic genes.