KB Cells Research Articles

Influence of Folate-Targeted Gold Nanoparticles on Subcellular Localization and Distribution into Lysosomes

The cell interaction, mechanism of cell entry and intracellular fate of surface decorated nanoparticles are known to be affected by the surface density of targeting agents. However, the correlation between nanoparticles multivalency and kinetics of the cell uptake process and disposition of intracellular compartments is complicated and dependent on a number of physicochemical and biological parameters, including the ligand, nanoparticle composition and colloidal properties, features of targeted cells, etc. Here, we have carried out an in-depth investigation on the impact of increasing folic acid density on the kinetic uptake process and endocytic route of folate (FA)-targeted fluorescently labelled gold nanoparticles (AuNPs). A set of AuNPs (15 nm mean size) produced by the Turkevich method was decorated with 0-100 FA-PEG3.5kDa-SH molecules/particle, and the surface was saturated with about 500 rhodamine-PEG2kDa-SH fluorescent probes. In vitro studies carried out using folate receptor overexpressing KB cells (KBFR-high) showed that the cell internalization progressively increased with the ligand surface density, reaching a plateau at 50:1 FA-PEG3.5kDa-SH/particle ratio. Pulse-chase experiments showed that higher FA density (50 FA-PEG3.5kDa-SH molecules/particle) induces more efficient particle internalization and trafficking to lysosomes, reaching the maximum concentration in lysosomes at 2 h, than the lower FA density of 10 FA-PEG3.5kDa-SH molecules/particle. Pharmacological inhibition of endocytic pathways and TEM analysis showed that particles with high folate density are internalized predominantly by a clathrin-independent process.

Effects of PEG-Linker Chain Length of Folate-Linked Liposomal Formulations on Targeting Ability and Antitumor Activity of Encapsulated Drug.

Ligand-conjugated liposomes are promising for the treatment of specific receptor-overexpressing cancers. However, previous studies have shown inconsistent results because of the varying properties of the ligand, presence of a polyethylene glycol (PEG) coating on the liposome, length of the linker, and density of the ligand. Here, we prepared PEGylated liposomes using PEG-linkers of various lengths conjugated with folate and evaluated the effect of the PEG-linker length on the nanoparticle distribution and pharmacological efficacy of the encapsulated drug both in vitro and in vivo. When folate was conjugated to the liposome surface, the cellular uptake efficiency in folate receptor overexpressed KB cells dramatically increased compared to that of the normal liposome. However, when comparing the effect of the PEG-linker length in vitro, no significant difference between the formulations was observed. In contrast, the level of tumor accumulation of particles in vivo significantly increased when the length of the PEG-linker was increased. The tumor size was reduced by >40% in the Dox/FL-10K-treated group compared to that in the Dox/FL-2K- or 5K-treated groups. Our study suggests that as the length of PEG-linker increases, the tumor-targeting ability can be enhanced under in vivo conditions, which can lead to an increase in the antitumor activity of the encapsulated drug.

Cytotoxicity Analysis for the Hydroxyl Functionalized MWCNT Reinforced PMMA Nanocomposites in Oral Squamous Carcinoma (KB) Cells.

In this particular research study, a unique three-dimensional mixing technique was used to incorporate multi-walled carbon nanotubes (MWCNTs) into polymethyl methacrylate (PMMA), and the KB cell line was used in the analysis of cytotoxicity, apoptosis detection, and cell viability using the MTT assay protocol. At low concentrations (0.001 to 0.1 g/mL), these results showed that the CNT did not seem to cause cell death or apoptosis directly. It increased lymphocyte-mediated cytotoxicity against KB cell lines. This was demonstrated by the fact that the CNT increased the time it took for KB cell lines to die. In the end, the unique three-dimensional mixing method solves problems such as clumping and uneven mixing that have been written about in the relevant literature. Phagocytic uptake of MWCNT-reinforced PMMA nanocomposite by KB cells leads to oxidative stress and apoptosis induction in a dose-dependent manner. The cytotoxicity of the generated composite and the ROS (reactive oxygen species) it produces may be controlled by adjusting the MWCNT loading. The conclusion that can be drawn from the studies to date is that it could be possible to treat some types of cancer using PMMA that has MWCNTs incorporated into it.

Garcowacinols A-J, cytotoxic polyprenylated benzoylphloroglucinol derivatives from the twigs of Garcinia cowa

Ten undescribed polyprenylated benzoylphloroglucinol derivatives named garcowacinols A‒J (1–10) and four known analogues (11–14) were isolated from the twigs of Garcinia cowa. Their structures were determined by spectroscopic data analysis (1D and 2D NMR and HRESIMS), and their absolute configurations were established based on NOESY and ECD data. All isolated compounds were evaluated for their cytotoxicity against five types of human cancer cells (KB, HeLa S3, MCF-7, Hep G2, and HT-29) as well as Vero cells by MTT colorimetric assay. Garcowacinol C was significantly active against all the five cancer cells with IC50 values in the range of 0.61–9.50 μM. Selective proliferative inhibitions were observed on garcowacinol F and 7-epiclusianone against KB cells, and guttiferone Q toward MCF-7 cells with IC50 values less than 10 μM.

Troxerutin, a Bioflavonoid Exhibits Oxidative Stress-induced Cytotoxic Effects on KB Cells

Abstract: Background: The prevalence of oral cancer is high and it is the sixth most occurring cancer in the world. Some of the drugs used to treat oral cancer cause adverse effects and are resistant to treatment. Objectives: This study was designed and performed to evaluate the cytotoxic and anti-cancerous effects of troxerutin. Materials and Methods: Cell proliferation, cell viability, and morphological analysis were performed with different doses of troxerutin. Once the IC50 value was obtained, doses were fixed and nitric oxide and lipid peroxidation were measured. Qualitative analysis of ROS and mitochondrial membrane potential was performed using 2′,7′-dichlorofluorescein methods and rhodamine 123 fluorescent staining respectively. Results: Troxerutin caused cytotoxicity and reduced cell viability. The IC50 value was 50 μg/ml. Morphological analysis revealed KB cells suffered after troxerutin treatment. Nitric oxide and TBARS levels were elevated. ROS concentration increased and mitochondrial membrane potential diminished with a higher concentration of the drug. Conclusion: Troxerutin exhibits an anti-cancer effect and can act as a NO-donating and ROS-promoting compound aiding in ch Conclusion:emotherapy. Keywords: Oral cancer, Troxerutin, Nitric oxide, Oxidative stress, Anti-cancer, Chemotherapy.

Intracellular calprotectin (S100A8/A9) facilitates DNA damage responses and promotes apoptosis in head and neck squamous cell carcinoma

ObjectivesIn head and neck squamous cell carcinoma (HNSCC), poor prognosis and low survival rates are associated with downregulated calprotectin. Calprotectin (S100A8/A9) inhibits cancer cell migration and invasion and facilitates G2/M cell cycle arrest. We investigated whether S100A8/A9 regulates DNA damage responses (DDR) and apoptosis in HNSCC after chemoradiation. Materials and methodsHuman HNSCC cases in TCGA were analyzed for relationships between S100A8/A9 and expression of apoptosis-related genes. Next, S100A8/A9-expressing and non-expressing carcinoma lines (two different lineages) were exposed to genotoxic agents and assessed for 53BP1 and γH2AX expression and percent of viable/dead cells. Finally, S100A8/A9-wild-type and S100A8/A9null C57BL/6j mice were treated with 4-NQO to induce oral dysplastic and carcinomatous lesions, which were compared for levels of 53BP1. ResultsIn S100A8/A9-high HNSCC tumors, apoptosis-related caspase family member genes were upregulated, whereas genes limiting apoptosis were significantly downregulated based on TCGA analyses. After X-irradiation or camptothecin treatment, S100A8/A9-expressing carcinoma cells (i.e., TR146 and KB-S100A8/A9) showed significantly higher 53BP1 and γH2AX expression, DNA fragmentation, proportions of dead cells, and greater sensitivity to cisplatin than wild-type KB or TR146-S100A8/A9-KD cells. Interestingly, KB-S100A8/A9Δ113-114 cells showed similar 53BP1 and γH2AX levels to S100A8/A9-negative KB and KB-EGFP cells. After 4-NQO treatment, 53BP1 expression in oral lesions was significantly greater in calprotectin+/+ than S100A8/A9null mice. ConclusionsIn HNSCC cells, intracellular calprotectin is strongly suggested to potentiate DDR and promote apoptosis in response to genotoxic agents. Hence, patients with S100A8/A9-high HNSCC may encounter more favorable outcomes because more tumor cells enter apoptosis with increased sensitivity to chemoradiation therapy.

Evaluation of the Cytotoxicity effects of ethanolic extract of Ferula assafoetida resin on oral Squamous Cells Carcinoma (KB) compared with L929 cells

One of the most common forms of malignancy is oral squamous cell carcinoma (OSCC). Despite advances in cancer treatment, the mortality rate of OSCC has remained almost unchanged for the past decades. Improving treatment requires the search for new classes of safer and more effective anticancer agents. Oleo-gum-resin obtained from Ferula assafoetida has significant anticancer properties against various cancer cells. The current study aims to evaluate the cytotoxic effects of the oleo-gum-resin extract on oral squamous cell carcinoma (KB) compared with normal mouse fibroblast cells (L929). The KB (cancer group) and L929 (control group) cells were cultured in an enriched RPMI-1640 medium. Then the cells were treated with 5 - 160 μg/ml concentrations of oleo-gum-resin extract for 24, 48, and 72 hours. The cell viability rate was determined by MTT assay. The statistical data analysis was done using SPSS software and the one-way ANOVA technique. Tukey’s comparison procedure was used to compare individual means. A t-test was used to compare the identical concentrations between two cell lines. In this study, IC50 was 37.36 and 89.81 µg/ml for KB and L929 cells, respectively. The IC50 ratio for normal (L929)-to-tumoral (KB) cells was 89.81: 37.36 = 2.40, indicating that a 2.5-fold higher effect of asafoetida extract on normal mouse fibroblast cells (L929) compared tumoral cells (KB). According to the results, the ethanolic asafoetida extract exhibited more cytotoxic effects on KB than on L929 cells. This study demonstrated that the asafoetida extract exerted more cytotoxic effects on oral squamous cell carcinoma than normal cells.

Separation and Purification of Antioxidant Peptide from Fermented Whey Protein by Lactobacillus rhamnosus B2-1.

In this study, a antioxidant activity peptide fraction was separated and purified from metabolites of whey protein fermented by Lactobacillus rhamnosus B2-1. The fermentation sample was separated by macroporous resin D101 and Sephadex G-15. The collected fractions were tested for antioxidant and antitumor activities. In order to test the antioxidant activity of fractions, Hydroxyl (·OH), 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS), and Oxygen Radical Absorbance Capacity (ORAC) were used. The final purified peptide B11 showed highest ABTS and ·OH radical scavenging rate by 84.36±1.89% and 62.43±2.64%, respectively, and had an ORAC activity of 1,726.44± 2.76 μM Trolox equivalent/g. Further, the inhibitory effect of B11 on the proliferation of LoVo human colon cancer cells, KB and Cal-27 human oral cancer cells were enhanced with increasing concentrations of B11. B11 contains 51.421% amino acids, with Glu and Asp being the major constituents. In this study, we obtained peptide fraction B11 with antioxidant activity, which is promising for development.

An invitro evaluation of the cytotoxicity and p53-mediated apoptotic effect of ocimum sanctum leaves hexane extract on human oral cancer cell lines

Background Oral cancer is one of the most common cancers and the leading cause of cancer deaths worldwide. Florae have been inspiration of salutary sources for curing ailments since ages. Hence, the contemporary investigation was aimed at evaluating the anti-proliferative activity of extract of Ocimum sanctum leaves on oral cancer KB mouth cell line. Methods Extract preparation using soxhlet apparatus, DPPH assay for antioxidant activity, Anticancer activity and western blotting for p53 expression. Results The obtained results showed that the methanol and hexane extracts of Ocimum sanctum (Tulsi) showed better activity in DPPH assay when compared with the rest. In anticancer activity against KB cell line and cytotoxicity activity in L132 cell line which was carried out by MTT assay; Ocimum sanctum (Tulsi) Hexane extract showed IC50 value of 74.39 for KB cell line and IC50 value of 431.39 for L132 cell line. The expression of p53 gene in KB cell line showed increased level of p53 denotes its upregulation has a cascade effect on regulation of apoptosis. Conclusion Thus substantiating the claim that it has evidenced anti oral cancer potential, which is promising but needs additional wet lab validations and characterization to isolate the phyto molecule and qualify it as a potential lead.This promising lead could be further taken up for bio activity studies of the purified phytomolecules from the plant for in vivo testing as a potential safe herbal based alternative therapeutics for oral cancer.

Construction of a pH/Temperature dual-responsive drug delivery platform based on exfoliated MoS2 nanosheets for effective delivery of doxorubicin: Parametric optimization via central composite design

The aim of the current work was to develop drug delivery system for encapsulation and release of doxorubicin using exfoliated molybdenum disulfide nanosheets modified N-isopropyl acrylamide/methyl methacrylate. Here, glutamine was conjugated to the surface of molybdenum disulfide nanosheets. Several techniques such as Fourier transform infrared spectroscopy, X-ray diffraction, thermal gravimetric analysis, field emission scanning electron microscopy, and Zeta potential were applied to characterize the nanoadsorbent. Three important parameters of pH, contact time, and temperature were optimized by the response surface methodology technique. According to the central composite design, the maximum adsorption efficiency of 95% is attained at the pH = 8, contact time of 15 min, and temperature of 30 °C. The non-linear isotherms and kinetics sorption of drug onto nanoadsorbent can be excellently simulated by the Freundlich isotherm model and pseudo-second-order kinetic models, respectively. The dual-responsive nanocarrier indicated a slow release profile in simulated blood fluid at pH = 7.4 (T = 37 °C), whereas 98% of drug was released when nanocarrier were dissolved in pH = 5.6 (T = 50 °C) after 6 h, showing a sustained pH and temperature dependent drug release. The biocompatibility of nanocarrier was evaluated by MTT assay on KB cell line as a breast cancer modal cell.

Evaluation of Bioactive Attributes and Emulsification Potential of Exopolysaccharide Produced by a Brown-rot Fungus Fomitopsis meliae AGDP-2.

Mushrooms possess wide array of biologically active secondary metabolites and have been traditionally used for their medicinal properties. Exopolysaccharide (EPS) is one of such bioactive metabolites. The bioactive attributes and emulsification capabilities of the exopolysaccharides produced by a novel brown-rot fungus Fomitopsis meliae AGDP-2 under submerged fermentation has been thoroughly investigated in the present study. Exopolysaccharide displayed anti-oxidant activities in dose dependent manner with the maximum scavenging of ABTS radicals (42.45%), DPPH radicals (75.34%), Hydroxyl radicals (63.64%), Superoxide anion radical (76.54%) and Ferric Reducing Antioxidant Power with IC50 value of 231µg/mL. Additionally, evaluation of anti-proliferative properties revealed that EPS significantly inhibited the proliferation of HepG2 and HT-29 cancer cells followed by moderate inhibition of HeLa and MCF-7 cancer cell lines and quite less inhibition of L-132 and KB cell lines. The IC50 values of EPS for the abovementioned cell lines are 9.465µg/mL, 11.25µg/mL, 38.98µg/mL, 87.78µg/mL, 2061µg/mL and 2361µg/mL respectively. Moreover EPS also possess good anti-microbial as well as anti-biofilm properties. The studies on emulsification potential described that EPS is good emulsifier of different vegetable oils and the emulsion formed was quite stable up to 144h.

Introducing a novel chemotherapeutic supplement prepared by silver nanoparticles green-formulated by Salvia officinalis leaf aqueous extract to treat the human oral squamous cell carcinoma

• A clear peak at the wavelength of 448 nm confirms the nanoparticles formation. • The peaks related to the aliphatic O-H and C-H stretching, C=C, C=O and Ag-O are at the wavelengths of 3507, 2913, 1369, 1665 and 462 cm -1 . • The average size of 50-90 nm was recorded. This research displays the synthesis of Silver nanoparticles (Ag NPs) by Salvia officinalis . The structural features of the synthesized nanocomposite were investigated by FT-IR, FE-SEM, UV-Vis studies. MTT assay was used on common human oral squamous cell carcinoma cell lines i.e., KB, HSC-4, HSC-3, HSC-2, and Ca9-22 to survey the cytotoxicity and anti-human oral squamous cell carcinoma effects of the synthesized nanocomposite. The synthesized nanocomposite had very low cell viability and high anti-human oral squamous cell carcinoma activities dose-dependently against KB, HSC-4, HSC-3, HSC-2, and Ca9-22 cell lines without cytotoxicity on the normal cell line (HUVEC). To determine the antioxidant properties of the synthesized nanocomposite, the DPPH test was used in the presence of butylated hydroxytoluene as the positive control. The synthesized nanocomposite inhibited half of the DPPH molecules in the concentration of 181 µg/mL. Maybe significant anti-human oral squamous cell carcinoma potentials of the synthesized nanocomposite against common human oral squamous cell carcinoma cell lines are linked to their antioxidant activities.

Folate receptor-targeted near-infrared photodynamic therapy for folate receptor-overexpressing tumors.

Photodynamic therapy (PDT) is a minimally invasive form of cancer therapy, and the development of a novel photosensitizer (PS) with optimal properties is important for enhancing PDT efficacy. Folate receptor (FR) membrane protein is frequently overexpressed in 40% of human cancer and a good candidate for tumor-specific targeting. Specific active targeting of PS to FR can be achieved by conjugation with the folate moiety. A folate-linked, near-infrared (NIR)-sensitive probe, folate-Si-rhodamine-1 (FolateSiR-1), was previously developed and is expected to be applicable to NIR-PDT. To investigate the therapeutic efficacy of NIR-PDT induced by FolateSiR-1, a FR-targeted PS, in preclinical cancer models. FolateSiR-1 was developed by conjugating a folate moiety to the Si-rhodamine derivative through a negatively charged tripeptide linker. FR expression in the designated cell lines was examined by western blotting (WB). The selective binding of FolateSiR-1 to FR was confirmed in FR overexpressing KB cells (FR+) and tumors by fluorescence microscopy and in vivo fluorescence imaging. Low FR expressing OVCAR-3 and A4 cell lines were used as negative controls (FR-). The NIR light (635 ± 3 nm)-induced phototoxic effect of FolateSiR-1 was evaluated by cell viability imaging assays. The time-dependent distribution of FolateSiR-1 and its specific accumulation in KB tumors was determined using in vivo longitudinal fluorescence imaging. The PDT effect of FolateSiR-1 was evaluated in KB tumor-bearing mice divided into four experimental groups: (1) FolateSiR-1 (100 μmol/L) alone; (2) FolateSiR-1 (100 μmol/L) followed by NIR irradiation (50 J/cm2); (3) NIR irradiation (50 J/cm2) alone; and (4) no treatment. Tumor volume measurement and immunohistochemical (IHC) and histological examinations of the tumors were performed to analyze the effect of PDT. High FR expression was observed in the KB cells by WB, but not in the OVCAR-3 and A4 cells. Substantial FR-specific binding of FolateSiR-1 was observed by in vitro and in vivo fluorescence imaging. Cell viability imaging assays showed that NIR-PDT induced cell death in KB cells. In vivo longitudinal fluorescence imaging showed rapid peak accumulation of FolateSiR-1 in the KB tumors 2 h after injection. In vivo PDT conducted at this time point caused tumor growth delay. The relative tumor volumes in the PDT group were significantly reduced compared to those in the other groups [5.81 ± 1.74 (NIR-PDT) vs 12.24 ± 2.48 (Folate-SiR-1), vs 11.84 ± 3.67 (IR), vs 12.98 ± 2.78 (Untreated), at Day 16, P < 0.05]. IHC analysis revealed reduced proliferation marker Ki-67-positive cells in the PDT treated tumors, and hematoxylin-eosin staining revealed features of necrotic- and apoptotic cell death. FolateSiR-1 has potential for use in PDT, and FR-targeted NIR-PDT may open a new effective strategy for the treatment of FR-overexpressing tumors.

Nanostructured lipid carrier-loaded metformin hydrochloride: Design, optimization, characterization, assessment of cytotoxicity and ROS evaluation

Metformin hydrochloride (MET) is commonly used in diabetes treatment. Recently, it has gained interest for its anticancer potential against a wide range of cancers. Owing to its hydrophilic nature, the delivery and clinical actions of MET are limited. Therefore, the present work aims to develop MET-encapsulated NLCs using the hot-melt emulsification and probe-sonication method. The optimization was accomplished by 33 BB design wherein lipid ratio, surfactant concentration, and sonication time were independent variables while the PS (nm), PDI, and EE (%) were dependent variables. The PS, PDI, % EE and ZP of optimized GMSMET-NLCs were found to be 114.9 ± 1.32 nm, 0.268 ± 0.04 %, 60.10 ± 2.23 %, and ZP − 15.76 mV, respectively. The morphological features, DSC and PXRD, and FTIR analyses suggested the confirmation of formation of the NLCs. Besides, optimized GMSMET-NLCs showed up to 88 % MET release in 24 h. Moreover, GMSMET-NLCs showed significant cell cytotoxicity against KB oral cancer cells compared with MET solution as shown by the reduction of IC50 values. Additionally, GMSMET-NLCs displayed significantly increased intracellular ROS levels suggesting the GMSMET-NLCs induced cell death in KB cells. GMSMET-NLCs can therefore be explored to deliver MET through different routes of administration for the effective treatment of oral cancer.

Palladium (II), platinum (II) and silver (I) complexes with oxazolines: Their synthesis, characterization, DFT calculation, molecular docking and antitumour effects

Six new Pd(II), Pt(II) and Ag(I) complexes, (1);{Pd (L1)]2C6H4}2Cl4} (2); Pt(L2)(DMSO)Cl; 3; {PtL5]2C6H4}2·PhCOO-⋅11NO3-; 4; {[Pt(L4)]2C6H4}; the binuclear cyclometalated complex the polymer chain (5); {[PtL5]C6H4}·NO3-}; and the polymeric silver species (6); Zn(L6)2·AgNO3·CHCl3 were synthesized and thoroughly characterized using X-ray diffraction and spectroscopic techniques (L1=(S,S)-1,4-i-PrOx]2C6H4}2Cl4, L2=Di(2,2-bis(4R-isopropyl-4,5-dihydro-oxazol-2-yl)acetonitrile) zinc (II) (BR1);L3= 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene (AR2); L4= 1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)benzene，L5=1,4-bis(4R-benzyl-4,5-dihydro-oxazol-2-yl)-benzene，L6=Di(2,2-bis(4S-isopropyl-4,5-dihydrooxazol-2-yl)acetonitrile) zinc (II).Complexes 1-6 showed cytotoxic effects against human tumour cell lines, including a multidrug-resistant subline. Oxazoline and Pd complex 1 induced apoptosis in A549 cells. DFT calculations were also performed to exhibit the excellent bioactivity of complex 1 against A549, MDA-MB-231, and KB cells. Complex 1, with the best docking score and a stable interaction network within the binding site of the G-quadruplex, could stably interact with the G-quadruplex. Additionally, complex 1 was further used in the animal experiment of human lung adenocarcinoma cells in nude mice. By comparing with the model control group, the tumour volume, relative tumour volume and relative tumour proliferation rate T/C decreased significantly in the cisplatin group and compound 1 (complex 1) group.

Cyclometalated platinum(II) complexes bearing natural arylolefin and quinolines ligands: Synthesis, characterizations, and in vitro cytotoxicity

Nine new cyclometalated platinum(II) complexes of the formula [PtCl(arylolefin)(Q)] (2, 3) and [Pt(arylolefin)(N,O)] (4–10) (arylolefinH: eugenoxyacetic acid, isopropyl eugenoxyacetate; Q: quinoline; (N,OH): quinolin-8-ol, 2-methylquinolin-8-ol, 5,7-dichloroquinloin-8-ol and quinoline-2-carboxylic acid] were synthesized and fully characterized by EA, ESI mass spectrometry, IR and NMR spectroscopy and single-crystal X-ray diffraction for 3, 7 and 10. The results show that the arylolefin binds with PtIIvia the C5 atom of the phenyl ring and the CC allyl in all the synthesized complexes. Quinoline coordinates with PtIIvia its N atom in 2, 3, while deprotonated (N,OH) coordinates with PtIIvia both the N and O atoms in 4–10. The N atom of Q and (N,O) in all complexes are at the cis position with respect to the allyl group of the arylolefin. The XRD confirms the square-planar coordination of PtII and trans position of the arylolefin and quinoline ligands. The results of in vitro cytotoxicity tests against human cancer cell lines KB and Lu of 2, 4–8 indicate that 4 and 5 exhibit the highest activities against Lu and KB cell lines with the IC50 values of 7.1 and 4.1 µM, respectively, which are approximately 6 and 4 times lower than cisplatin.

EVALUATION OF ANTI TUMORIGENIC ACTIVITY OF Boswelliaserrata USING KB CELL LINE

Background: B.serrata is commonly known as Indian olibanum, it is mainly used in the production of Indian frankincense. B.serrata is used for many other purposes including asthma diabetes. The medicinal plant Boswelliaserrata has great potential for treating cancer. Since many cancer therapies have their origins in natural ingredients, this study aims to explore the anti-tumorigenic effect of B.serrata using KB cell line.Materials and methods: Seed of B.serrata was collected and extraction was done. Then the extract was added to the culture and the oral cancer cells were obtained from Pune. The cultured oral cells were incubated in a CO2 incubator. Treated oral cancer cell sample was done MTT assay and gene expression analysis.Result: The collected data from MTT assay and gene expression analysis tabulated using SPSS software. MTT assay results showed gradual decrease in cell viability with increase in concentration of Boswelliaserrata and the gene expression showed up regulation of caspase 3 and 9 expression.Conclusion: From the study, Boswelliaserrata has a significant effect on anti-tumorigenic activity; this might be due to the active bio components present in Boswelliaserrata extract.

Erianin inhibits oral cancer cell growth, migration, and invasion via the Nrf2/HO-1/ GPX4 pathway

Objective: To evaluate the effect of erianin on the viability, migration, and invasion of KB cells and elucidate its underlying mechanisms. Methods: Cell Counting Kit-8, colony formation, wound healing, and Transwell assays were used to determine the proliferation, migration, and invasion of oral cancer KB cells. Furthermore, malondialdehyde (MDA) and glutathione (GSH) levels were determined. Fluorescent probes were used to detect changes in intracellular reactive oxygen species and iron ions. Additionally, the expressions of ferroptosis-related proteins, NF-E2-related factor 2 (Nrf2), ferritin heavy chain 1 (FTH1), heme oxygenase 1 (HO-1), and glutathione peroxidase 4 (GPX4) were analyzed by Western blotting assays. Results: Erianin induced ferroptosis and inhibited the proliferation, migration, and invasion of KB cells. Moreover, erianin decreased GSH level, increased MDA level, elevated intracellular ROS and Fe2+ contents, and downregulated the expression of the ferroptosis-related proteins Nrf2, HO-1, GPX4, and FTH1 in KB cells. These effects of erianin were effectively reversed by a ferroptosis inhibitor, ferrostatin-1. Conclusions: Erianin inhibits the proliferation, migration, and invasion of oral cancer cells and induces ferroptosis via the Nrf2/HO-1/GPX4 signaling pathway. Therefore, erianin may be a potential candidate for the treatment of oral cancer.

Design, synthesis and characterization of novel Benzothiazolyl pyrazoles as potential antitubercular scaffold

The present study validates the synthesis of two new series of benzothiazole conjugated pyrazole analogs by the coupling of benzothiazole hydrazine with 4-formyl pyrazole derivatives, which was set up by Vilsmeier-Haack reaction. The synthetic approach was initiated by coupling different acetophenones and phenyl hydrazine to synthesize the Schiff's bases, which further undergo cyclization with Vilsmeier-Haack reagent followed by the imine formation. A singlet at 7.1 ppm in 1 H NMR indicated the protons of azo methane linkage (Schiff's base formation). Synthesized compounds were characterized by FT-IR, LC-MS, 1 H NMR and 13 C NMR spectroscopic techniques. The peak at 1593 cm −1 (>C=N-) indicated the formation of the azo methane linkage in the synthesized compounds. In 1 H NMR spectroscopy, a singlet peak at 8.89 ppm indicated the pyrazole proton, which confirmed the presence of 5-membered pyrazole ring.The recently synthesized compounds were screened for the anticancer and anti-tubercular (anti-TB) activities. MIC values of the compounds for in-vitro anti-TB activity were 1.6 μg/ml and MIC value of the compounds for in-vitro anti-cancer activities were 67.65 µg/ml and 70.31 µg/ml, against HELA and KB cell lines respectively. Most active compounds were found to be less toxic, which was determined by MTT assay method with normal cell line (L292). Biological screening of the synthesized series of compounds reveals that, Compound 5b was the potent molecule. .

Synthesis and Cytotoxic Evaluation of Fluoro and Trifluoromethyl Substituents Containing Novel Naphthoquinone-Fused Podophyllotoxins

A series of novel naphthoquinone-fused podophyllotoxins containing fluoro and trifluoromethyl substituents were synthesized in a medium with good yields using two different synthetic approaches: microwave-assisted four-component reactions of 2-hydroxy-1,4-naphthoquinone, tetronic acid, fluorinated arylaldehydes, and ammonium acetate, and microwave-assisted three-component reactions of 2-amino-1,4-naphthoquinone, tetronic acid, and fluorinated arylaldehydes. The structures of all products were confirmed by spectral analysis. Together, cytotoxicity assessment of the products against four human cancer cell lines (human carcinoma [KB], human hepatocellular carcinoma [HepG2], lung cancer [A549], breast carcinoma [MCF7], and human embryonic kidney [Hek-293]) was performed by MTT assay. Among the obtained compounds, compound 7f turned out to be the most potent anticancer agent with significant cytotoxic activity against KB, HepG2, and MCF cancer cell lines.