KB Oral Cancer Cells Research Articles

Argyreia nervosa (Samudra pala) leaf extract mediated silver nanoparticles and evaluation of their antioxidant, antibacterial activity, in vitro anticancer and apoptotic studies in KB oral cancer cell lines

In the present investigation, green synthesis of silver nanoparticles (AgNPs) was carried out using aqueous leaf extract of Argyreia nervosa. The results of the spectral characterisation have revealed that the surface Plasmon resonance band was observed at 421 nm confirms the formation of AgNPs. The Fourier Transform Infra-red Spectroscopy result shows the reduction of silver nitrate into AgNPs by the reduction of different functional groups. Transmission Electron Microscope analysis revealed that the particles are roughly spherical and poly-disperse in shape and size, the particles are within the size range of 10–55 nm. Dynamic Light Scattering revealed that the nanoparticles were also within the range of 10–50 nm, An-AgNPs have a high negative zeta potential value of −38.9 mV. An-AgNPs showed efficient free radical scavenging activity and showed excellent antimicrobial activity. Anti-proliferative and cytotoxic effect of An-AgNPs was carried out by MTT assay against KB oral cancer cells, the IC50 value of An-AgNPs is 58.64 µg/ml. The cell's growth is arrested at the G2/M phase, so the An-AgNPs activated the Caspase 3 pathway which leads to the Apoptosis of KB oral cancer cells. So it is concluded that the green synthesised An-AgNPs have manifold functions.

Cytotoxicity and Cellular Uptake of 5-Fluorouracil Loaded Methylcellulose Nanohydrogel for Treatment of Oral Cancer

The objective of the study was to investigate the cytotoxicity and cellular uptake of prepared 5-Fluorouracil (5-FU) nano hydrogel formulation using KB oral cancer cell line and VERO fibroblast cell line. The biodegradable thermoresponsive modified methylcellulose (MMC) polymer was used for the preparation of nano hydrogel, whereas it shows a sol-gel phase transition at 36˚C to 40˚C. The physical crosslinking method was used, followed by probe sonication for the preparation of 5-FU loaded MMC nano hydrogel. The mechanism of crosslinking was studied by FT-IR and SEM. These experimental techniques explained physical crosslinking viz. H-bonding phenomenon with the interconnected porous structure of nanoscale pore size. Cytotoxicity assay in the concentration range from 1 µg/ml to 2000µg/ml shows an IC50 value at around 250µg/ml. This nano hydrogel shows concentration-dependent toxicity to the cancer cells while they were less toxic to normal fibroblast VERO cells. Cellular uptake was confirmed by the green fluorescence inside cells by Rhodamine-B conjugation using a fluorescent microscope. These results depict that 5-FU loaded thermosensitive nano hydrogel may be a promising candidate for intratumoral targeted drug delivery to cancer cells.

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.

Anticancer and antiproliferative efficacy of a standardized extract of Vaccinium macrocarpon on the highly differentiating oral cancer KB cell line athwart the cytotoxicity evaluation of the same on the normal fibroblast L929 cell line.

Background and Objectives:The perpetual search is on to find botanical complementary adjuncts to the conventional therapies used that is not only cost-effective but also reduces side effects associated with conventional synthetic drugs that are available in the market. The aim of this study was to assess the in vitro anticancer efficacy of hydroalcoholic fruit extract of cranberry against oral cancer KB cell line by Di-Methyl Thiazoldiphenyl Tetrazolium bromide assay (MTT) assay and its cytotoxicity on normal fibroblast cells.Materials and Methods:Vaccinium macrocarpon extract was prepared using a hydroethanolic solvent (water – 30%:ethanol – 70%) using the standardized maceration protocol. Standard KB and normal fibroblast (L929) cell lines were used. The minimum lethal effect of the extract was calculated using the MTT cytotoxicity assay.Results:The extract shows a satisfactory antiproliferative effect on the KB cell line and a higher cell viability percentage of the normal fibroblast cell line.Conclusion:V. macrocarpon can prove to be an adjunct to the existing anticancer drug therapy against oral cancer KB cell line.

DESIGN, SYNTHESIS AND EVALUATION OF 6-SUBSTITUTED-4-HYDROXY-1-(2- SUBSTITUTEDACETYL)-3-NITROQUINOLIN-2(1H)-ONES FOR ANTICANCER ACTIVITY

The present work deals with the synthesis of a series of 6-substituted-4-hydroxy-1-(2-substitued alicyclicaminoacetyl)-3-nitroquinolin-2(1H)-one {IVa-d (1-3)} derivatives and evaluation of their in vitro anticancer activity. Docking study was carried out using EGFR-tyrosine kinase binding site (PDB ID: 1m17) and revealed encouraging results. The sequence of reactions consists of the initial synthesis of 6-substituted 4-hydroxyquinolin-2(1H)-ones (Ia-d), which were further subjected to nitration reaction to give 6- substituted-4-hydroxy-3-nitroquinolin-2(1H)-one (IIa-d). Condensation of compounds (IIa-d) with chloroacetyl chloride resulted in 6-substituted-1-(2-chloroacetyl)-4-hydroxy-3-nitroquinolin-2(1H)-one(IIIa-d), which was subjected to substitution reaction using various secondary amines to yield the title compounds {IVa-d (1-3)}. All the synthesized compounds were characterized by IR, NMR and mass spectral data.All the derivatives were tested for their in vitro anticancer activity using KB (oral cancer) cell lines. Among the synthesized compounds, compound (IVc-2) was found to be the most cytotoxic as compared to the other synthesized derivatives, with IC50 values of 0.2406μM/mL against KB cell line.

Bio-modified TiO2 nanoparticles with Withania somnifera, Eclipta prostrata and Glycyrrhiza glabra for anticancer and antibacterial applications.

Titanium dioxide nanoparticles exhibit good anticancer and antibacterial activities. They are known to be environmentally friendly and stable, less toxic and excellent biocompatibility nature. In this paper we report the biological properties of pure TiO2 nanoparticles modified with Withania somnifera (Ashwagandha), Eclipta prostrata (Karisalankanni) and Glycyrrhiza glabra (Athimathuram) for biological applications. X-ray diffraction results revealed the anatase nature of the samples. From the TEM analyses, it is observed that there is an increase in the particle size of the bio modified samples. UV results show the red shift for the bio modified samples when compared with the pure samples. The samples are then subjected to MTT assay to determine the cell viability. KB oral cancer cells are used for the determination of anticancer nature of the pure and bio modified nanoparticles. It is observed that Withania somnifera - Eclipta prostrate modified TiO2 nanoparticles exhibit excellent anticancer activities among other bio modified and pure samples. The samples are then examined for their antibacterial activities against three Gram-negative bacterial strains namely, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and two Gram-positive bacterial strains namely, Staphylococcus aureus and Streptococcus mutans. Among the modified and pure samples, Withania somnifera - Eclipta prostrata showed good antibacterial nature against Gram-positive and Gram-negative bacteria.

Syntheses and characterization of Syzygium aromaticum, Elettaria cardamomum and Cinnamomum verum modified TiO2 and their biological applications

Diseases form the major roadblock for the living organism. Many chemicals are isolated to cure diseases. But they are found to have side effects due to allergetic chemicals. NPs are found to be good biological agents. But they are also allergetic in nature. In this study, the properties of TiO2 NPs were modified with bio agents such as Clove, Elachi (Cardamom) and Cinnamon. The anticancer and antibacterial properties were also examined. XRD analysis showed the anatase phase for the pure and modified TiO2 samples. The particle sizes were found to be 7.5 nm for pure, 9.5 nm for Clove modified, 9 nm for Elachi modified and 10.5 nm for Cinnamon modified TiO2 NPs. The synthesized TiO2 nanoparticles were tested against bacterial strains such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus and Streptococcus mutans using agar diffusion method for antibacterial studies. KB Oral cancer cell line was used to determine the anticancer activities of the synthesized NPs by MTT assay. The synthesized bio modified NPs exhibit significant results against bacterial strains and cancer cell line when compared with the pure NPs.

C-Myc Overexpression Promotes Oral Cancer Cell Proliferation and Migration by Enhancing Glutaminase and Glutamine Synthetase Activity

BackgroundThis study aimed to investigate whether glutaminase (GLS) and glutamine synthetase (GS) are involved in c-Myc-mediated tumor development in oral cancer. MethodsThe correlation between the expressions of c-Myc, GLS, and GS in clinical samples and the clinicopathologic features of oral cancer were examined using immunohistochemistry and quantitative real-time polymerase chain reaction. After overexpressing the c-Myc gene and using an inhibitor of GLS or GS, functional experiments were performed to confirm the effects of c-Myc, GLS and GS on proliferation, cell cycle and migration in KB oral cancer cells. The expressions of E-cadherin and N-cadherin were determined by immunofluorescence assays in KB cells overexpressing c-Myc in the presence of GLS or GS inhibitors. ResultsThe protein expression of GS was correlated with the Tumor, Lymph Node, and Metastasis (TNM) stage. In addition, c-Myc mRNA levels were positively correlated with GS mRNA levels. Overexpression of c-Myc increased the colonies derived from oral cancer cells and caused more cells to be in S phase compared with the mock-vehicle group. The migratory speed of KB cells was promoted by overexpression of c-Myc compared to the mock-vehicle group. However, these effects were effectively reversed in the presence of GLS or GS inhibitor. Furthermore, c-Myc could inhibit E-cadherin protein expression while promoting N-cadherin expression by enhancing the activity of GLS and GS. Conclusionsc-Myc overexpression promotes oral cancer cell proliferation and migration by enhancing GLS and GS activity. Our findings are beneficial for the identification of novel molecular targets for the prevention and treatment of oral cancer.

Effects of chrysin on the apoptosis in oral squamous carcinoma KB cell line and the underlying mechanisms

To investigate the effect of chrysin on apoptosis of oral squamous carcinoma KB cell line and the possible mechanisms, and to provide new ideas for the treatment of oral cancer. Methods: Oral cancer KB cells were treated with different concentrations of chrysin (1, 2, 4, 8, 16, and 32 μmol/L) for 24 h. Cell proliferation was detected by MMT assay; apoptosis was detected by flow cytometry; the activity of caspase-3/7 was detected by chemiluminescent assay; mitochondrial membrane potential in KB cells was determined by JC-1 assay; and Western blotting was used to determine the activation of protein kinase B (AKT) and phosphoinositide-3-kinase (PI3K). Results: Chrysin inhibited the proliferation of KB cells in a concentration-dependent manner, accompanied by increase in apoptosis of KB cells, activation of caspase-3/7, decrease in mitochondrial membrane potential, and suppression of the phosphorylation of AKT and PI3K. Conclusion: The effect of chrysin on KB cell apoptosis may be related to mitochondrial dysfunction and inhibition of PI3K/AKT pathway.

Hydrothermal synthesis of pure and bio modified TiO2: Characterization, evaluation of antibacterial activity against gram positive and gram negative bacteria and anticancer activity against KB Oral cancer cell line

Titanium dioxide nanoparticles were found to be good anticancer and antibacterial agents. In this study, the antibacterial and anticancer activities of pure TiO2, turmeric, ginger and garlic modified TiO2 nanoparticles were investigated. X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR) and UV–visible spectroscopy were used to analyze the samples. Antibacterial activities were performed against five bacterial strains namely Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruoginosa, Staphylococcus aureus and Streptococcus mutans. The modified TiO2 nanoparticles exhibited enhanced antibacterial activity when compared with pure TiO2 samples and anticancer activities for the samples were performed in KB Oral cancer cell line. The results of the modified TiO2 NPs indicate a greater efficacy on anticancer and antibacterial properties compared to the pure TiO2 NPs.

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.].

Palladium-catalyzed domino sequence for the synthesis of N-aryl quinolinone-3-carboxylate derivatives and their anti-proliferative activity

An efficient and an operationally simple Palladium-catalyzed domino reaction for the synthesis of N-aryl quinolinone-3-carboxylate derivatives has been developed via the reaction between diethyl 2-(2-bromobenzylidine) malonate and anilines. These newly synthesized compounds exhibited good to moderate anti-proliferative activity with GI50 values ranging from 0.41µM to 45.77µM. Among them, compounds 6j, 6k and 6m demonstrated potential activity particularly against MCF-7 (breast) and KB (oral) cancer cell lines.

Lactobacillus plantarum induces apoptosis in oral cancer KB cells through upregulation of PTEN and downregulation of MAPK signalling pathways.

Introduction: The oral tumor is the sixth most prevalent type of cancer worldwide and the second leading cause of cancer-related mortality. Although chemotherapy and immunotherapy are the main strategies for the treatment of oral cancer, an emergence of inevitable resistance to these treatment modalities is the major drawback that causes recurrence of the disease. Nowadays, probiotics have been suggested as adjunctive and complementary treatment modalities for improving the impacts of chemotherapy and immunotherapy agents. Probiotics, the friendly microflora in our bodies, contribute to the production of useful metabolites with positive effects on the immune system against various diseases such as cancer. Methods: Lactobacillus plantarum is one of the most important bacteria, which commensally live in the human oral system. In the current study, the impacts of L. plantarum on maintaining oral system health were investigated, and the molecular mechanisms of inhibition of oral cancer KB cells mediated by L. plantarum were evaluated using real-time polymerase chain reaction (PCR) and FACS flow cytometry analyses. Results: Our findings showed that L. plantarum is effective in the signal transduction of the oral cancer cells through upregulation and downregulation of PTEN and MAPK pathways, respectively. Conclusion: Based on the biological effects of oral candidate probiotics candidate bacterium L. plantarum on functional expression of PTEN and MAPK pathways, this microorganism seems to play a key role in controlling undesired cancer development in the oral system. Taken all, L. plantarum is proposed as a potential candidate for probiotics cancer therapy.

MiR-214 regulates oral cancer KB cell apoptosis through targeting RASSF5.

Ras association domain family member 5 (RASSF5), a member of the Ras association domain family, induces cell apoptosis by phosphorylating FOXO3a, which triggers target gene BIM (pro-apoptotic factor) activation. MiR-214 is overexpressed in oral cancer tissue, indicating its possible involvement in oral cancer pathogenesis. Bioinformatics analysis has revealed a complimentary sequence between miR-214 and the 3'-UTR of RASSF5 mRNA. However, whether miR-124 regulates RASSF5 in oral cancer remains poorly understood. We aimed to investigate the role of miR-214 in RASSF5 expression regulation in oral cancer. Tumor and paracarcinoma tissues were obtained from 48 oral cancer patients to examine miR-214 and RASSF5 expression. The relationship between miR-214 and RASSF5 was investigated by dual luciferase reporter gene assay. Oral cancer KB cells were cultured in vitro and divided into inhibitor NC, miR-214 inhibitor, Scramble-pMD18, RASSF5-pMD18, and miR-214 inhibitor + RASSF5-pMD18 groups. Caspase 3 activity, cell apoptosis, and total protein expression were measured by spectrophotometry, flow cytometry, and western blot, respectively. MiR-214 expression was significantly increased, while that of RASSF5 decreased in oral cancer tumor tissues compared to paracarcinoma tissues. Luciferase assay showed that miR-214 suppressed RASSF5 expression by targeting its 3'-UTR. Down-regulation of miR-214 and/or enhancement of RASSF5 expression markedly increased FOXO3a phosphorylation, BIM expression, caspase 3 activity, and apoptosis. In conclusion, miR-214 expression was elevated and RASSF5 was down-regulated in oral cancer. Moreover, miR-214 regulated KB cell apoptosis through targeted inhibition of RASSF5 expression, FOXO3a phosphorylation, and BIM expression, suggesting its possible application as a novel therapeutic oral cancer target.

Anti-proliferative and apoptotic effects of quinine in human Hep-2 laryngeal cancer and KB oral cancer cell

<p>The present study evaluated the anti-proliferative and apoptotic effect of quinine on oral cancer cells Hep-2 and KB. Cell inhibition, apoptosis and anti-inflammatory effects were explored by nuclear DNA cleavage, condensation, change in membrane potential of mitochondria. Meanwhile, inflammatory and apoptosis-related mRNA and proteins expressions such as iNOS COX-2, IL-6, Bcl-2, mutant p53, Bax, caspase-3 and NF-κB were determined by RT-PCR and Western blotting assays. Results showed that, quinine treatment significantly inhibited the cell viability and colony formation, inhibited cell proliferation lead to increased generation of reactive oxygen species induction of MMP depolarization, morphological changes and DNA damage in dose- and time-dependent manner. Moreover, quinine significantly decreased the iNOS, COX-2, IL-6, Bcl-2 and mutant p53 simultaneously up-regulated Bax, caspase-3 expressions through the inhibition of NF-κB suggest that quinine may serve as a potential candidate in the prevention of cell proliferation and enhances apoptosis via inhibiting up-stream signalling.</p><p><strong>Video Clip</strong></p><p><a href="https://youtube.com/v/83HX2fFTXkg">Programmed cell death assay by dual staining:</a> 17 min 25 sec</p><p> </p>

Anticancer potential of bioactive 16-methylheptadecanoic acid methyl ester derived from marine Trichoderma

The present work aimed at purifying the intracellular fungal metabolites, such as 16-methylheptadecanoic acid methyl ester (HDA) and 9,12-octadecadienoic acid (ODA) from marine Trichoderma, Hypocrea lixii TSK8, Hypocrea rufa SKS2 respectively, and investigating their anticancer and antioxidant effects. The two fungal metabolites were tested against two human cancer cell lines, namely oral cancer (KB) and skin carcinoma (A431) by using MTT assay. The inhibitory concentrations (IC50) against KB oral cancer cells were found to be 18.75±0.12μg/mL for HDA and 75.50±0.42μg/mL for ODA. Whereas IC50 values of HDA and ODA against A431 were found 37.5±0.42μg/mL and 72.89±0.15μg/mL, respectively. In addition, the down-regulation of heat shock protein 90kDa (HSP90) was confirmed by using SDS-PAGE and Western blot analysis. The effect of HDA induced apoptosis via ROS-dependent internucleosomal DNA fragmentation was confirmed by AGE analysis. We further evaluated the in vivo anti-skin cancer activity of HDA in Swiss albino mice induced with skin cancer by 7,12-dimethylbenz(a)anthracene (DMBA) and croton oil (CO). The in vivo hematological, biochemical and histopathological results revealed that the fungal metabolite HDA was a highly potent anticancer compound against the skin cancer.

Berberine induces FasL-related apoptosis through p38 activation in KB human oral cancer cells.

In the present study, we examined the anticancer properties of berberine in KB oral cancer cells with a specific focus on its cellular mechanism. Berberine did not affect the cell viability of the primary human normal oral keratinocytes that were used as a control. However, the viability of KB cells was found to decrease significantly in the presence of berberine in a dose-dependent manner. Furthermore, in KB cells, berberine induced the fragmentation of genomic DNA, changes in cell morphology, and nuclear condensation. In addition, caspase-3 and -7 activation, and an increase in apoptosis were observed. Berberine was also found to upregulate significantly the expression of the death receptor ligand, FasL. In turn, this upregulation triggered the activation of pro-apoptotic factors such as caspase-8, -9 and -3 and poly(ADP-ribose) polymerase (PARP). Furthermore, pro-apoptotic factors such as Bax, Bad and Apaf-1 were also significantly upregulated by berberine. Anti-apoptotic factors such as Bcl-2 and Bcl-xL were downregulated. Z-VAD-FMK, a cell-permeable pan-caspase inhibitor, suppressed the activation of caspase-3 and PARP. These results clearly indicate that berberine-induced cell death of KB oral cancer cells was mediated by both extrinsic death receptor-dependent and intrinsic mitochondrial-dependent apoptotic signaling pathways. In addition, berberine-induced upregulation of FasL was shown to be mediated by the p38 MAPK signaling pathway. We also found that berberine-induced migration suppression was mediated by downregulation of MMP-2 and MMP-9 through phosphorylation of p38 MAPK. In summary, berberine has the potential to be used as a chemotherapeutic agent, with limited side-effects, for the management of oral cancer.

Blueberry anthocyanins induce G2/M cell cycle arrest and apoptosis of oral cancer KB cells through down-regulation methylation of p53

Blueberries are an excellent source of dietary polyphenols such as anthocyanins and phenolic acids. In this study, we investigated the ability of anthocyanins from the wild blueberries of Inner Mongolia to suppress the growth of the oral cancer cell line KB. The blueberry anthocyanins were extracted with methanol-containing 0.1% (v/v) hydrochloric acid. Fourteen unique anthocyanins were identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS). The anticancer bioactivity of the extracts on KB cells was analyzed using methylthiazolyl-tetrazolium (MTT), flow cytometry (FCM) and immunocytochemistry. It was shown that the blueberry anthocyanins suppressed the proliferation of KB cells in a dose-dependent manner, as well as induced G2/M cell cycle arrest and apoptosis of oral cancer KB cells. Immunocytochemistry analysis showed that the expression of caspase-9 and cytochrome c were obviously increased after the anthocyanins treatment. Western blot analysis also indicated that the expression of p53 was increased. Methylation-specific PCR (MSP) showed that the amount of unmethylated p53 increased, indicating that the anthocyanins can down-regulate the methylation of p53.

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.