Carcinoma KB Cells Research Articles

Ecofriendly Curcumin-Conjugated Copper Oxide Nanoparticles: Targeted Cytotoxicity and Apoptosis in Oral Carcinoma KB Cells

Ecofriendly Curcumin-Conjugated Copper Oxide Nanoparticles: Targeted Cytotoxicity and Apoptosis in Oral Carcinoma KB Cells

Negative regulation of thyroid adenoma-associated protein (THADA) in the cardiac glycoside-induced anti-cancer effect

Cardiac glycosides, known as inhibitors of Na+,K+-ATPase, have anti-cancer effects such as suppression of cancer cell proliferation and induction of cancer cell death. Here, we examined the signaling pathway elicited by cardiac glycosides in the human hepatocellular carcinoma HepG2 cells and human epidermoid carcinoma KB cells. Three kinds of cardiac glycosides (ouabain, oleandrin, and digoxin) inhibited the cancer cell proliferation and decreased the expression level of thyroid adenoma-associated protein (THADA). Interestingly, the knockdown of THADA inhibited cancer cell proliferation, and the proliferation was significantly rescued by re-expression of THADA in the THADA-knockdown cells. In addition, the THADA-knockdown markedly decreased the expression level of L-type amino acid transporter LAT1. Cardiac glycosides also reduced the LAT1 expression. The LAT1 inhibitor, JPH203, significantly weakened the cancer cell proliferation. These results suggest that the binding of cardiac glycosides to Na+,K+-ATPase negatively regulates the THADA-LAT1 pathway, exerting the anti-proliferative effect in cancer cells.

Multifunctional curcumin mediated zinc oxide nanoparticle enhancing biofilm inhibition and targeting apoptotic specific pathway in oral squamous carcinoma cells.

Oral health remains a significant global concern with the prevalence of oral pathogens and the increasing incidence of oral cancer posing formidable challenges. Additionally, the emergence of antibiotic-resistant strains has complicated treatment strategies, emphasizing the urgent need for alternative therapeutic approaches. Recent research has explored the application of plant compounds mediated with nanotechnology in oral health, focusing on the antimicrobial and anticancer properties. In this study, curcumin (Cu)-mediated zinc oxide nanoparticles (ZnO NPs) were synthesized and characterized using SEM, EDAX, UV spectroscopy, FTIR, and XRD to validate their composition and structural features. The antioxidant and antimicrobial activity of ZnO-CU NPs was investigated through DPPH, ABTS, and zone of inhibition assays. Apoptotic assays and gene expression analysis were performed in KB oral squamous carcinoma cells to identify their anticancer activity. ZnO-CU NPs showcased formidable antioxidant prowess in both DPPH and ABTS assays, signifying their potential as robust scavengers of free radicals. The determined minimal inhibitory concentration of 40µg/mL against dental pathogens underscored the compelling antimicrobial attributes of ZnO-CU NPs. Furthermore, the interaction analysis revealed the superior binding affinity and intricate amino acid interactions of ZnO-CU NPs with receptors on dental pathogens. Moreover, in the realm of anticancer activity, ZnO-CU NPs exhibited a dose-dependent response against Human Oral Epidermal Carcinoma KB cells at concentrations of 10µg/mL, 20µg/mL, 40µg/mL, and 80µg/mL. Unraveling the intricate mechanism of apoptotic activity, ZnO-CU NPs orchestrated the upregulation of pivotal genes, including BCL2, BAX, and P53, within the KB cells. This multifaceted approach, addressing both antimicrobial and anticancer activity, positions ZnO-CU NPs as a compelling avenue for advancing oral health, offering a comprehensive strategy for tackling both oral infections and cancer.

Zinc oxide nanoparticles functionalized with cinnamic acid for targeting dental pathogens receptor and modulating apoptotic genes in human oral epidermal carcinoma KB cells.

Oral diseases are often attributed to dental pathogens such as S. aureus, S. mutans, E. faecalis, and C. albicans. In this research work, a novel approach was employed to combat these pathogens by preparing zinc oxide nanoparticles (ZnO NPs) capped with cinnamic acid (CA) plant compounds. The synthesized ZnO-CA NPs were characterized using SEM, FTIR, and XRD to validate their composition and structural features. The antioxidant activity of ZnO-CA NPs was confirmed using DPPH and ABTS free radical scavenging assays. The antimicrobial effects of ZnO-CA NPs were validated using a zone of inhibition assay against dental pathogens. Autodock tool was used to identify the interaction of cinnamic acid with dental pathogen receptors. ZnO-CA NPs exhibited potent antioxidant activity in both DPPH and ABTS assays, suggesting their potential as powerful antioxidants. The minimal inhibitory concentration of ZnO-CA NPs against dental pathogens was found 25µg/mL, indicating their effective antimicrobial properties. Further, ZnO-CA NPs showed better binding affinity and amino acid interaction with dental pathogen receptors. Also, the ZnO-CA NPs exhibited dose-dependent (5µg/mL, 15µg/mL, 25µg/mL, and 50µg/mL) anticancer activity against Human Oral Epidermal Carcinoma KB cells. The mechanism of action of apoptotic activity of ZnO-CA NPs on the KB cells was identified through the upregulation of BCL-2, BAX, and P53 genes. This research establishes the potential utility of ZnO-CA NPs as a promising candidate for dental applications. The potent antioxidant, anticancer, and effective antimicrobial properties of ZnO-CA NPs make them a valuable option for combating dental pathogens.

Swietemicrolides A-D, mexicanolide-type limonoids from the bark of Swietenia macrophylla with in vitro cytotoxic and α-glucosidase inhibitory activities.

Four new mexicanolide-type limonoids, swietemicrolides A-D (1-4), together with three known compounds (5-7) were isolated from an ethyl acetate extract of the bark of Swietenia microphylla. 1 and 2 had 1,8-hemiacetal systems whilst 3 and 4 shared hexacyclic skeletons consisting of three fused five-membered rings. The structures of the isolated compounds were determined using spectroscopic methods. The five limonoids (1-5) were tested in vitro for their cytotoxic effects against two human cancer cell lines (KB carcinoma and A549 lung cancer cells) and α-glucosidase inhibitory activity. None of them showed significant cytotoxic activity, however, swietemicrolide C (3) exhibited strong effect towards α-glucosidase. Moreover, a possible biosynthetic pathway for compounds 1-4 was proposed to support a comprehensive understanding of the configurations of the new limonoids.

Molecular perspective on starfish tissue extracts: Targeting human carcinoma KB cells for anticancer therapy

The marine environment is rich in natural bioactive compounds, including zebrafish and starfish species, which have garnered attention in drug research for their remarkable tissue regeneration abilities. Zebrafish, in particular, share a genetic resemblance of around 70% with humans. We chose to investigate Luidia maculata, a starfish species, due to its remarkable tissue regeneration abilities and the potential bioactive compounds it holds, making it a promising candidate for anticancer and antioxidant therapies. Human KB carcinoma cells were subjected to L. maculata tissue extracts to assess cytotoxicity using the MTT test. Intracellular ROS levels were measured via DCFH-DA, and mitochondrial membrane potential changes were evaluated using Rh-123 staining. Oxidative DNA damage was examined with the comet test, while morphological apoptotic changes were observed through the AO/EtBr dual staining technique. The active compounds in the starfish extracts were identified using HPLC, GC–MS/MS, and FTIR analyses.The bioactive fractions extracted from L. maculata demonstrated significant anti-proliferative effects on KB carcinoma cells, inducing apoptosis. These fractions led to a notable increase in intracellular ROS levels, resulting in alterations in mitochondrial membrane potential and oxidative DNA damage in the cells. Upregulation of Bax/Caspase 3 protein expression and downregulation of Bcl-2 protein expression indicated the involvement of apoptotic pathways. Comprehensive analyses confirmed 35 starfish-derived anticancer compounds that inhibit cell proliferation, induce apoptosis, and target cancer-related pathways. Additionally, our study underscores the antioxidant potential of L. maculata starfish extracts, offering insights into marine organism-based therapies with promising medical applications.

Mechanistic investigation of photodynamic therapy using Visudyne in human KB carcinoma cells

Photodynamic therapy is a therapy that utilizes a specialized drug, a photosensitizer, which is not toxic by itself, but upon activation with light, is activated and leads to the production of singlet oxygen species. This production of singlet oxygen species starts a cascade that leads to cell death. Photodynamic therapy is a potential treatment for cancer patients, and it might be helpful to promote human health by providing alternative treatment to cancer. In-vitro study with Visudyne (VD) in KB carcinoma cells unveiled the mechanism of cell injury to cell death upon photodynamic therapy (PDT). In this study, we investigated real time monitoring of the production of singlet oxygen (SO), reactive oxygen species (ROS), mitochondria integrity and chromatin integrity in VD treated live cells by irradiating with a mercury lamp light source and 665–675 nm and 480–560 nm emission filter. Upon PDT we also observed cytoskeleton remodeling and cytochrome –C release using immunofluorescence techniques. We investigate the cytotoxicity of PDT and performed quantitative analysis for SO, ROS and mitochondrial potential change using colocalization analysis between VD and mitochondria.

Synthesis and Structure-Activity Relationship of Salvinal Derivatives as Potent Microtubule Inhibitors.

Salvinal is a natural lignan isolated from the roots of Salvia mitorrhiza Bunge (Danshen). Previous studies have demonstrated its anti-proliferative activity in both drug-sensitive and -resistant cancer cell lines, with IC50 values ranging from 4-17 µM. In this study, a series of salvinal derivatives was synthesized and evaluated for the structure-activity relationship. Among the twenty-four salvinal derivatives, six compounds showed better anticancer activity than salvinal. Compound 25 displayed excellent anticancer activity, with IC50 values of 0.13-0.14 µM against KB, KB-Vin10 (overexpress MDR/Pgp), and KB-7D (overexpress MRP) human carcinoma cell lines. Based on our in vitro microtubule depolymerization assay, compound 25 showed depolymerization activity in a dose-dependent manner. Our findings indicate that compound 25 is a promising anticancer agent with depolymerization activity that has potential for the management of malignance.

Effect of PEG anchor in PEGylation of folate-modified cationic liposomes with PEG-derivatives on systemic siRNA delivery into the Tumor

In this study, we prepared small interfering RNA (siRNA)/cationic liposome complexes (lipoplexes) modified with folate (FA)-polyethylene glycol (PEG, MW 2000, 3400 or 5000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) to facilitate their uptake into tumor cells via folate receptor (FR), and with PEG1600-cholesterol (PEG1600-Chol) or PEG2000-chondroitin sulfate conjugate (PEG2000-CS), to enhance their systemic stability. Among the FA-PEG-modified siRNA lipoplexes, 0.5 mol% FA-PEG5000-DSPE-modified lipoplexes with 2.5 mol% PEG2000-CS or PEG1600-Chol (LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL, respectively) exhibited selective growth inhibition of human nasopharyngeal carcinoma KB cells through transduction with polo-like kinase 1 (PLK1) siRNA. Furthermore, the LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL lipoplexes exhibited decreased agglutination with erythrocytes through PEGylation, and markedly decreased the accumulation of siRNA in murine lungs after systemic injection. Finally, systemic injection of LP-0.5F5/2.5P2-CS and LP-0.5F5/2.5P1.6-CL lipoplexes resulted in accumulation of siRNA in KB tumor xenografts. These findings suggest that PEGylation of FA-PEG5000-DSPE-modified siRNA lipoplexes with PEG2000-CS or PEG1600-Chol might improve their systemic stability without the loss of selective transfection activity in tumor cells.

Synthesis, Cytotoxicity, ADMET and Molecular Docking Studies of Some Quinoline-Pyrimidine Hybrid Compounds: 3-(2-Amino-6-arylpyrimidin-4- yl)-4-hydroxy-1-methylquinolin-2(1H)-ones.

This study aims are the synthesis of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1- methylquinolin-2(1H)-ones and estimation their anticancer activities on HepG2 and KB cancer lines. Many derivatives of quinoline-2-on have been interested to synthesize and evaluate their biological properties by organic chemists due to their various biological effects, including antibacterial, antioxidant, anti-inflammatory, anticancer activities. Quinoline-pyrimidine hybrid compounds exhibited various biological activities, such as antituberculosis, antibacterial, anticancer, antifungal, etc. The connection of 4-hydroxyquinoline-2-one with 2-amino-pyrimidine could initiate the new activities. α,β-Unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one were prepared. Novel 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines have been synthesized by reaction of these corresponding α,β-unsaturated ketones with guanidine hydrochloride. Human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines were used for screening their cytotoxicity. 3-Acetyl-4-hydroxy-N-methylquinolin-2-one was prepared from N-methylaniline and diethyl malonate. Reaction of (un)substituted benzaldehydes with this 4-hydroxyquinoline-2-one produced corresponding substituted α,β-unsaturated ketones in the presence of piperidine as catalyst. 2- Amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines have been synthesized from these α,β-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding α,β-unsaturated ketones with guanidine hydrochloride. All obtained pyrimidines were screened for anticancer activity using MTT bio-assay method. Seven substituted (E)-4-hydroxy-3-(3-(aryl)acryloyl)-1-methylquinolin-2(1H)-ones were prepared and converted to corresponding substituted 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin- 2'-on-3'-yl)pyrimidines with yields of 58-74%. All the synthesized pyrimidines were screened for their in vitro anticancer activity against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC50 values equal to 1.32 and 1.33 μM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f possessed the drug-likeness behavior. Cross-docking results indicated that residues GLN778(A), DT8(C), DT9(D), DA12(F), and DG13(F) in the binding pocket as potential ligand binding hot-spot residues for compounds 6b, 6e, and 6f. New substituted 2-amino-6-aryl-4-(4'-hydroxy-N-methylquinolin-2'-on-3'-yl)pyrimidines were obtained and displayed significant inhibition against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines.

Scutellarein apoptosis mediated by mitochondria in oral squamous cell carcinomas

Background: The growth of several cancers can be inhibited by naturally occurring medicinal plants. A flavone called Scutellarein found in the perennial herb Scutellaria lateriflora does have a wide range of biological functions. Scutellarein was studied to determine whether it could induce apoptosis and cause cytotoxicity. Methods: On oral squamous cell carcinoma KB cell lines, Scutellarein's cytotoxic activity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. Scutellarein was added to KB cells at concentrations ranging from 25 to 125 g/mL for 24 h. The real-time polymerase chain reaction was also used to investigate apoptotic induction potential in Scutellarein-incubated KB cell lines by analyzing Bcl-2 protein and gene expression. Results: In KB-cell lines treated with scutellarein, cytotoxicity and anticancer effects were observed, as well as inhibit the growth of cancer cells. In comparison to the cells not treated with scutellarein, KB cells that had been exposed to scutellarein displayed reduced Bcl-2 expression. Conclusion: KB cells were treated with scutellarein to induce apoptosis, suggesting its potential as a chemo preventative agent. This activity appears to be mediated through the modulation of Bcl-2, a cytotoxic gene.

Regulation of Jun and Fos AP-1 transcription factors by JNK MAPKs signaling cascade in areca nut extract treated KB cells

The edible endosperm of Areca catechu is recognized as a potent carcinogenic agent either consumed alone or in combination with tobacco. Habitual chewing of areca nut leads to orally potential malignant disorders which are highly effective in malignant transformation and thereby lead to oral carcinogenesis. Human buccal epithelial KB carcinoma cells were used as an experimental cell system to inspect the mechanistic act of aqueous extract of areca nut on biochemical status and their implications on transcriptional activation of cancer signaling cascade that could possibly trigger numerous oncogenic players and finally decides the cells fate. Extract treated cells showed reduced viability with altered balance between oxidants and antioxidants which lead to redox status and which is known to distort various biological processes within the cell system. Results of RT-PCR demonstrated decreased expression of BCl2, cell cycle regulators along with Activator Protein −1 (AP-1) components. While Bax, p16 and p21 mRNAs showed increased expression in extract treated KB cells. Likewise, the translational levels of proliferation cell nuclear antigen (PCNA), tumor suppressor p53, retinoblastoma (Rb) and cyclin dependent kinase 4 (CDK4) were decreased along with AP-1 subunits (c-Jun/c-Fos) with increased protein levels of p21 in extract treated KB cells. Further, the downstream activation and regulation of AP-1 transcription factors could be through stress activated c-Jun – N terminal Kinase (JNK) Mitogen Activated Protein Kinases (MAPKs) which downregulated both Jun and Fos mRNA transcripts in areca nut extract exposed KB cells. Thus, outcome of the study provides insights into mechanistic path of pathogenesis of areca related disorders. Further, it could aid in designing new therapeutic modalities that specific targets these oncogenic players and help in disease management.

Synthesis and Characterization of Radiogallium-Labeled Cationic Amphiphilic Peptides as Tumor Imaging Agents.

Simple SummaryCationic amphiphilic peptides (CAPs), such as SVS-1, exhibit preferential cytotoxicity towards cancer cells. SVS-1 can also be used as a diagnostic tool for the detection of cancer. Here, we report the development of three 67Ga-labeled SVS-1 derivatives as potential cancer diagnostic agents. All of these radiotracers showed high accumulation in cancerous KB cells. Notably, the uptake of 67Ga-NOTA-KV6 and 67Ga-NOTA-HV6 into 3T3-L1 fibroblasts was significantly lower than in KB cells. In vivo biodistribution studies showed that 67Ga-NOTA-KV6, 67Ga-NOTA-RV6, and 67Ga-NOTA-HV6 exhibit high tumor accumulation, tumor/blood ratios (3.8–8.0), and tumor/muscle ratios (3.3–5.0) 120 min after administration. These radiolabeled SVS-1 analogues target the surface membranes of cancer cells, and are prospective scaffolds for in vivo imaging agents.SVS-1 is a cationic amphiphilic peptide (CAP) that exhibits a preferential cytotoxicity towards cancer cells over normal cells. In this study, we developed radiogallium-labeled SVS-1 (67Ga-NOTA-KV6), as well as two SVS-1 derivatives, with the repeating KV residues replaced by RV or HV (67Ga-NOTA-RV6 and 67Ga-NOTA-HV6). All three peptides showed high accumulation in epidermoid carcinoma KB cells (53–143% uptake/mg protein). Though 67Ga-NOTA-RV6 showed the highest uptake among the three CAPs, its uptake in 3T3-L1 fibroblasts was just as high, indicating a low selectivity. In contrast, the uptake of 67Ga-NOTA-KV6 and 67Ga-NOTA-HV6 into 3T3-L1 cells was significantly lower than that in KB cells. An endocytosis inhibition study suggested that the three 67Ga-NOTA-CAPs follow distinct pathways for internalization. In the biodistribution study, the tumor uptakes were found to be 4.46%, 4.76%, and 3.18% injected dose/g of tissue (% ID/g) for 67Ga-NOTA-KV6, 67Ga-NOTA-RV6, and 67Ga-NOTA-HV6, respectively, 30 min after administration. Though the radioactivity of these peptides in tumor tissue decreased gradually, 67Ga-NOTA-KV6, 67Ga-NOTA-RV6, and 67Ga-NOTA-HV6 reached high tumor/blood ratios (7.7, 8.0, and 3.8, respectively) and tumor/muscle ratios (5.0, 3.3, and 4.0, respectively) 120 min after administration. 67Ga-NOTA-HV6 showed a lower tumor uptake than the two other tracers, but it exhibited very low levels of uptake into peripheral organs. Overall, the replacement of lysine in SVS-1 with other basic amino acids significantly influenced its binding and internalization into cancer cells, as well as its in vivo pharmacokinetic profile. The high accessibility of these peptides to tumors and their ability to target the surface membranes of cancer cells make radiolabeled CAPs excellent candidates for use in tumor theranostics.

Synthesis and cytotoxicity of substituted aromatic curcuminoids against human oral epidermal carcinoma-KB cell line

Introduction: The survival rate of oral cancer, like other types of cancers, has not been improved regardless of the early diagnosis and the introduction of advanced therapies. Treatment for oral cancer includes surgery, radiation therapy, and chemotherapy. However, the effectiveness has been limited due to recurrence and undesirable side effects. Metabolites from plant sources have been shown to be relatively less toxic and thus are considered as potential anti-cancer agents. Interestingly, curcumin isolated from the rhizome of Curcuma longa L. possesses broad-spectrum bioactivities. We focused on the synthesis of curcumin-based analogs bearing -OH/-OCH3/-F groups on the phenyl rings in our continuous efforts to search for curcumin-based anti-cancer agents. The synthesized compounds were subsequently evaluated for the cytotoxic activities against KB cancer cell line (an epidermal carcinoma of the mouth).
 Methods: The desired curcuminoids were synthesized via aldol reactions between benzaldehyde derivatives and pentane-2,4-dione using n-butylamine as a catalyst. Structures were distinguished by NMR and MS spectra. The cytotoxic activity against KB was determined through the half-maximal inhibitory concentration (IC50, mM).
 Results: Six curcumin analogs (1-6) were successfully synthesized in a yield of 48-76%. The 3- hydroxy/fluoro curcumin analogs (3, IC50 = 15.61 0.13 mM; 6, IC50 = 22.65 1.76 mM) exhibited better anti-cancer activities when compared to curcumin (1, IC50 = 33.35 2.66 mM), whereas the para-fluoro substitution patterns displayed lower inhibitory activities (4, 5) against KB cancer cell line.
 Conclusions: The synthetic yields are dependent on the position and nature of substituents in aromatic rings. The presence of electron-donating groups gives products (1-3) in lower yields when compared to those (4-6) prepared from fluorinated benzaldehydes as starting materials. The curcuminoids bearing -OH groups at para-positions in aromatic rings (1, 2) can be responsible for better inhibition of cell growth, whereas the fluoro-substituted compounds (4, 5) make a negative contribution to inhibitory activity. Furthermore, the contributions -OH/-F groups at meta-position in aromatic rings of (3, 6) on the cytotoxicity against KB are remarkable and firstly reported in our findings.

Design, Synthesis and Anticancer Activity of New Polycyclic: Imidazole, Thiazine, Oxathiine, Pyrrolo-Quinoxaline and Thienotriazolopyrimidine Derivatives.

In this article, we showed the synthesis of new polycyclic aromatic compounds, such as thienotriazolopyrimidinones, N-(thienotriazolopyrimidine) acetamide, 2-mercapto-thienotriazolo-pyrimidinones, 2-(((thieno-triazolopyrimidine) methyl) thio) thieno-triazolopyrimidines, thieno-pyrimidotriazolo-thiazines, pyrrolo-triazolo-thienopyrimidines, thienopyrimido-triazolopyrrolo-quinoxalines, thienopyrimido-triazolo-pyrrolo-oxathiino-quinoxalinones, 1,4-oxathiino-pyrrolo- triazolothienopyrimidinones, imidazopyrrolotriazolothienopyrimidines and 1,2,4-triazoloimidazo- pyrrolotriazolothienopyrimidindiones, based on the starting material 2,3-diamino-6-benzoyl-5- methylthieno[2,3-d]pyrimidin-4(3H)-one (3). The chemical structures were confirmed using many spectroscopic ways (IR, 1H, 13C, −NMR and MS) and elemental analyses. A series of thiazine, imidazole, pyrrole, thienotriazolopyrimidine derivatives were synthesized and evaluated for their antiproliferative activity against four human cancer cell lines, i.e., CNE2 (nasopharyngeal), KB (oral), MCF-7 (breast) and MGC-803 (gastric) carcinoma cells. The compounds 20, 19, 17, 16 and 11 showed significant cytotoxicity against types of human cancer cell lines.

Quinoline-pyrimidine hybrid compounds from 3-acetyl-4-hydroxy-1-methylquinolin-2(1H)-one: Study on synthesis, cytotoxicity, ADMET and molecular docking

Some novel 2-amino-6-aryl-4-(4′-hydroxy-N-methylquinolin-2′-on-3′-yl)pyrimidines have been synthesized from α,β-unsaturated ketones of 3-acetyl-4-hydroxy-N-methylquinolin-2-one by reaction of corresponding α,β-unsaturated ketones with guanidine hydrochloride. The purity and structure of the obtained products have been confirmed by thin layer chromatography, IR, 1H NMR, 13C NMR, HSQC, HMBC and MS spectra. All the synthesized of 3-(2-amino-6-arylpyrimidin-4-yl)-4-hydroxy-1-methylquinolin-2(1H)-ones 6a-i were screened for their in vitro cytotoxic activity against human hepatocellular carcinoma HepG2 and squamous cell carcinoma KB cancer lines. Compounds 6b and 6e had the best activity in the series, with IC50 values equal to 1.33 μM. Compounds 6a-g exhibited weak or insignificant activity with liver cancer cell lines HepG2, while compounds 6a and 6g had more powerful activity in this sequence, with IC50 values equal to 47.99 and 89.38 μM, respectively. ADMET properties showed that compounds 6b, 6e, and 6f possessed the drug-likeness behavior. Cross-docking results indicated that two hydrogen bonding interactions in the binding pocket, as potential ligand binding hot-spot residues for compounds 6b and 6e, may be one of the mechanisms of action responsible for the higher cytotoxic effect on HepG2 and KB cells.

Fe3O4@Au/reduced graphene oxide nanostructures: Combinatorial effects of radiotherapy and photothermal therapy on oral squamous carcinoma KB cell line

Combination therapy including radiotherapy (RT) and photothermal therapy (PTT), as an alternative treatment for cancer treatment, recently has generated substantial interest. Graphene-based nanocarbons and gold content metallic nanoparticles, as one of the most attractive materials with their extraordinary physical and chemical properties, are extremely useful in this regard. We herein reported the effects of combination of cancer therapy including RT (doses of 2 and 4 Gy) and PTT (808 nm laser irradiation, NIR irradiation) as radio-photothermal therapy (RPTT) of KB oral squamous carcinoma cell line in the presence of Fe3O4@Au/reduced graphene oxide (rGO) nanostructures (NSs) at different concentrations. Fe3O4@Au/rGO NSs with different rGO contents have been synthesized by hydrothermal reaction method. They characterized by XRD, FE-SEM, TEM, EDS, FTIR and TGA. Cell viability for cytotoxicity, RT, PTT and RPTT were studied by MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyltetrazolium bromide) assay. High photothermal conversion efficiency of Fe3O4@Au/rGO NSs reaches to 61%. The resulting Fe3O4@Au NPs with approximate size of about 10–60 nm covered the rGO nanosheets with 40 wt% rGO at concentration of 20 μg ml−1, exhibited satisfactory cytotoxicity. They provided significant cell destruction under RT, PTT and specially RPTT in dose of 4 Gy. Furthermore, they have good biocompatibility on the healthy cells. Our results show that Fe3O4@Au/rGO NSs integrated with radiosensitization, photothermal therapy and their combination promising for nanomedicine and clinical applications.

Impaired actin filaments decrease cisplatin sensitivity via dysfunction of volume-sensitive Cl- channels in human epidermoid carcinoma cells.

Cisplatin is a widely used platinum-based anticancer drug in the chemotherapy of numerous human cancers. However, cancer cells acquire resistance to cisplatin. So far, functional loss of volume-sensitive outwardly rectifying (VSOR) Cl- channels has been reported to contribute to cisplatin resistance of cancer cells. Here, we analyzed protein expression patterns of human epidermoid carcinoma KB cells and its cisplatin-resistant KCP-4 cells. Intriguingly, KB cells exhibited higher β-actin expression and clearer actin filaments than KCP-4 cells. The β-actin knockdown in KB cells decreased VSOR Cl- currents and inhibited the regulatory volume decrease (RVD) process after cell swelling. Consistently, KB cells treated with cytochalasin D, which depolymerizes actin filaments, showed smaller VSOR Cl- currents and slower RVD. Cytochalasin D also inhibited cisplatin-triggered apoptosis in KB cells. These results suggest that the disruption of actin filaments cause the dysfunction of VSOR Cl- channels, which elicits resistance to cisplatin in human epidermoid carcinoma cells.

Cordyceps militaris fraction inhibits angiogenesis of hepatocellular carcinoma in vitro and in vivo

Background: Cordyceps militaris fraction (CMF) was found to inhibit the proliferation of chronic myeloid leukemia K562 cells, oral squamous carcinoma KB cells, and the metastasis of lung cancer cells. This study focuses on the activity of CMF against angiogenesis of hepatocellular carcinoma (HCC). Objectives: The objective of the study is to research the antiangiogenic activity of CMF in HCC cells and the underlying mechanism in vitro and in vivo. Materials and Methods: Transwell migration and invasion assays were used to measure the effects of CMF on migration and invasion of SMMC-7721 cells and human umbilical vein endothelial cells (HUVECs). Tube formation and rat aortic ring assays were used to assess the antiangiogenic potential of CMF. The antiangiogenic mechanism was detected by immunofluorescence and western blot analysis. The nude mice xenografted with SMMC-7721 cells were used to study the antiangiogenic activity of CMF and its underlying mechanism in vivo. Immunohistochemistry analysis was used to evaluate the effect of CMF on the expression of CD31, and western blot analysis was also performed to detect the expression of vascular endothelial growth factor (VEGF) and other related proteins in tumor tissues. Results: CMF inhibited the migration and invasion of SMMC-7721 cells and HUVECs and suppressed VEGF-induced tube formation of HUVECs and the formation of aortic ring capillaries of rats in a concentration-dependent manner. CMF attenuated the phosphorylation of VEGF receptor 2 (VEGFR2), Akt, and ERK in SMMC-7721 cells and HUVECs. CMF significantly inhibited tumor growth in nude mice xenografted with SMMC-7721 cells. CMF reduced the expression level of CD31, western blot analysis indicated that CMF downregulated the expression of VEGFR2 and attenuated the phosphorylation of Akt and ERK in the tumor tissues, which was consistent with the results obtained from in vitro study. Conclusion: CMF can inhibit the angiogenesis of HCC and the mechanism is associated with suppression of the VEGF/VEGFR2 signaling pathway.

Diterpenoids and Flavonoids from Andrographis paniculata.

Chemical investigation of the aerial parts of Andrographis paniculata resulted in isolation of nine compounds, including a new ent-labdane diterpenoid, andrographic acid methyl ester (1), a new chalcone glucoside, pashanone glucoside (5), and seven known metabolites, andrograpanin (2), andrographolide (3), andropanolide (4), andrographidine A (6), andrographidine F (7), 6-epi-8-O-acetyl-harpagide (8), and curvifloruside F (9). Their chemical structures were elucidated based on comprehensive analyses of the spectroscopic data, including NMR and MS. Among the isolated compounds, andropanolide exerted cytotoxicity toward LNCaP, HepG2, KB, MCF7, and SK-Mel2 carcinoma cells, with IC50 values ranging from 31.8 to 45.9 µM. In addition, andropanolide significantly inhibited the overproduction of nitric oxide (NO) in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages, with an IC50 value of 13.4 µM.