Human Epidermoid Carcinoma Cell Line Research Articles

Novel alloxazine analogues: design, synthesis, and antitumour efficacy enhanced by kinase screening, molecular docking, and ADME studies

This study describes the development of novel alloxazine analogues as potent antitumor agents with enhanced selectivity for tumour cells. Twenty-nine out of 45 newly compounds were investigated in vitro for their growth inhibitory activities, against two human tumour cell lines, namely, the human T-cell acute lymphoblastoid leukaemia cell line (CCRF-HSB-2) and human oral epidermoid carcinoma cell line (KB), and the antitumor agent “Ara-C” was used as a positive reference in this investigation. Compounds 9e and 10J were the highest among their analogues, against both tumour cell lines (CCRF-HSB-2 and KB). Correlation analyses demonstrated a strong relationship between the IC50 values and AutoDock binding free energy or calculated inhibition (Ki ). The study delves into structure–activity relationships (SARs) through advanced modelling tools integrated with structure-based drug design (SBDD) using GOLD 5.2.2, AutoDock 4.2, and Accelrys Discovery Studio 3.5. Physicochemical properties, pharmacokinetics, drug-likeness, and toxicity predictions of the most potent alloxazine derivatives were conducted using ProTox-II and Swiss ADME for effective antitumor agents with improved selectivity.

Lawsone attenuates acute low dose ethanol-induced skin inflammation in A431 epidermoid carcinoma skin cells and its possible mechanisms in targeting interleukin (IL)-1α in silico

Standard treatment for acute skin inflammatory conditions comes with unwanted side effects. Traditionally, Lawsonia inermis has been used to treat skin-related ailments, with lawsone as the main active phytochemical is predicted to inhibit a skin pro inflammatory cytokine, IL-1α. This study is aimed to evaluate the anti- inflammatory effect of lawsone in acute ethanol-induced skin inflammatory condition in vitro, by targeting IL-1α in silico. Basically, the IC50 of lawsone on human epidermoid carcinoma cell line (A431) was obtained by using MTT proliferation assay, followed by acute low dose ethanol-induced inflammatory skin condition on A431 cells to determine cell viability. Next, molecular docking study was done by utilizing Autodock Vina software, and further analyzed by ProteinsPlus and PyMol softwares. Meaningful interaction that exist in the binding of lawsone to IL-1α was determined by molecular docking results comparison with two other compounds (kirenol and curcumin diglucoside). In vitro study showed the IC50 of lawsone in low cytotoxicity level at 150 µM. Skin anti-inflammatory assay indicated that lawsone has highly significant (p<0.05) anti-inflammatory activity at 9.375 µM at low concentration, but not effective at higher concentrations (more than 18.75 µM). In silico studies indicated binding of lawsone to IL-1α with top binding affinity of -5.2 kcal/mol, at binding residues of Asp65 and Ile68. Docking comparison analysis to determine meaningful interaction comparison indicated three key IL-1α binding residues common to most tested compounds, such as Ile68 and Asp65 thus supported the predicted mechanistic pathway. This highlighted lawsone potential as a future skin anti-inflammatory agent with minimal toxicity.

Evaluation of antiproliferative activity of Naringin in Human epidermoid carcinoma cell line (A431)

Evaluation of antiproliferative activity of Naringin in Human epidermoid carcinoma cell line (A431)

Synthesis and biological evaluation of novel benzothiazole derivatives as potential anticancer and antiinflammatory agents.

Introduction: Cancer, a significant global health concern, necessitates innovative treatments. The pivotal role of chronic inflammation in cancer development underscores the urgency for novel therapeutic strategies. Benzothiazole derivatives exhibit promise due to their distinctive structures and broad spectrum of biological effects. This study aims to explore new anti-tumor small molecule drugs that simultaneously anti-inflammatory and anticancer based on the advantages of benzothiazole frameworks. Methods: The compounds were characterized by nuclear magnetic resonance (NMR), liquid chromatograph-mass spectrometer (LC-MS) and high performance liquid chromatography (HPLC) for structure as well as purity and other related physicochemical properties. The effects of the compounds on the proliferation of human epidermoid carcinoma cell line (A431) and human non-small cell lung cancer cell lines (A549, H1299) were evaluated by MTT method. The effect of compounds on the expression levels of inflammatory factors IL-6 and TNF-α in mouse monocyte macrophages (RAW264.7) was assessed using enzyme-linked immunosorbent assay (ELISA). The effect of compounds on apoptosis and cell cycle of A431 and A549 cells was evaluated by flow cytometry. The effect of compounds on A431 and A549 cell migration was evaluated by scratch wound healing assay. The effect of compounds on protein expression levels in A431 and A549 cells was assessed by Western Blot assay. The physicochemical parameters, pharmacokinetic properties, toxicity and drug similarity of the active compound were predicted using Swiss ADME and admetSAR web servers. Results: Twenty-five novel benzothiazole compounds were designed and synthesized, with their structures confirmed through spectrogram verification. The active compound 6-chloro-N-(4-nitrobenzyl) benzo[d] thiazol-2-amine (compound B7) was screened through a series of bioactivity assessments, which significantly inhibited the proliferation of A431, A549 and H1299 cancer cells, decreased the activity of IL-6 and TNF-α, and hindered cell migration. In addition, at concentrations of 1, 2, and 4μM, B7 exhibited apoptosis-promoting and cell cycle-arresting effects similar to those of the lead compound 7-chloro-N-(2, 6-dichlorophenyl) benzo[d] thiazole-2-amine (compound 4i). Western blot analysis confirmed that B7 inhibited both AKT and ERK signaling pathways in A431 and A549 cells. The prediction results of ADMET indicated that B7 had good drug properties. Discussion: This study has innovatively developed a series of benzothiazole derivatives, with a focus on compound B7 due to its notable dual anticancer and anti-inflammatory activities. B7 stands out for its ability to significantly reduce cancer cell proliferation in A431, A549, and H1299 cell lines and lower the levels of inflammatory cytokines IL-6 and TNF-α. These results position B7B7 as a promising candidate for dual-action cancer therapy. The study's mechanistic exploration, highlighting B7's simultaneous inhibition of the AKT and ERK pathways, offers a novel strategy for addressing both the survival mechanisms of tumor cells and the inflammatory milieu facilitating cancer progression.

Development of an Antiviral Ion-Activated In Situ Gel Containing 18β-Glycyrrhetinic Acid: A Promising Alternative against Respiratory Syncytial Virus.

The human respiratory syncytial virus (hRSV) is a major cause of serious lower respiratory infections and poses a considerable risk to public health globally. Only a few treatments are currently used to treat RSV infections, and there is no RSV vaccination. Therefore, the need for clinically applicable, affordable, and safe RSV prevention and treatment solutions is urgent. In this study, an ion-activated in situ gelling formulation containing the broad-spectrum antiviral 18β-glycyrrhetinic acid (GA) was developed for its antiviral effect on RSV. In this context, pH, mechanical characteristics, ex vivo mucoadhesive strength, in vitro drug release pattern, sprayability, drug content, and stability were all examined. Rheological characteristics were also tested using in vitro gelation capacity and rheological synergism tests. Finally, the cytotoxic and antiviral activities of the optimized in situ gelling formulation on RSV cultured in the human laryngeal epidermoid carcinoma (HEp-2) cell line were evaluated. In conclusion, the optimized formulation prepared with a combination of 0.5% w/w gellan gum and 0.5% w/w sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between the first day of the experiment (T0) and the last day of the experiment (T14) was 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53 Pa), mechanical characteristics (adhesiveness: 0.300 ± 0.05 mJ), ex vivo bioadhesion force (19.67 ± 1.90 g), drug content uniformity (RSD%: 0.494), and sustained drug release over a period of 6 h (24.56% ± 0.49). The optimized formulation demonstrated strong anti-hRSV activity (simultaneous half maximal effective concentration (EC50) = 0.05 µg/mL; selectivity index (SI) = 306; pre-infection EC50 = 0.154 µg/mL; SI = 100), which was significantly higher than that of ribavirin (EC50 = 4.189 µg/mL; SI = 28) used as a positive control against hRSV, according to the results of the antiviral activity test. In conclusion, this study showed that nasal in situ gelling spray can prevent viral infection and replication by directly inhibiting viral entry or modulating viral replication.

Biphasic response of epidermoid adenocarcinoma cells to curcumin and EGCG co-treatment

We investigated the combinatorial treatment of curcumin and epigallocatechin-gallate (EGCG) in human epidermoid carcinoma cell line A-431. When combined, concentrations of EGCG and curcumin lower than 25 μM increased proliferation, but 50 μM curcumin led to near complete proliferation/viability inhibition. As reference, the compounds were CCD-1070Sk, where they did not show any toxicity, except in the highest concentration sample. In A-431 cell line, curcumin and EGCG combinations induced cell death by apoptosis, collapse of thee also tested on normal FIbroblast cells, mitochondrial membrane depolarization (ΔΨm) and increase the cell number in S phase of cell cycle. Nevertheless, the most powerful compound in inducing the above effects was curcumin. Next, we have shown that EGCG scavenged ROS produced by 25 μM curcumin with an EC50 of 44.34 μM EGCG. In conclusion, curcumin and EGCG combinations exert ΔΨm collapse, cell death and cell cycle arrest in A-431 cells at concentrations not affecting the viability of normal skin fibroblasts.

Synthesis and in vitro photodynamic activity of aza-BODIPY-based photosensitizers.

Aza-BODIPY dyes have recently come to attention owing to their excellent chemical and photophysical properties. In particular, their absorption and emission maxima can efficiently be shifted to the red or even to the NIR spectral region. On this basis, aza-BODIPY derivatives are widely investigated as fluorescent probes or phototherapeutic agents. Here we report the synthesis of a set of novel aza-BODIPY derivatives as potential photosensitizers for use in photodynamic therapy. Triazolyl derivatives were obtained via Cu(I)-catalyzed azide-alkyne cycloaddition as the key step. In vitro photodynamic activities of the newly synthesized compounds were evaluated on the A431 human epidermoid carcinoma cell line. Structural differences influenced the light-induced toxicity of the test compounds markedly. Compared to the initial tetraphenyl aza-BODIPY derivative, the compound bearing two hydrophilic triethylene glycol side chains showed substantial, more than 250-fold, photodynamic activity with no dark toxicity. Our newly synthesized aza-BODIPY derivative, acting in the nanomolar range, might serve as a promising candidate for the design of more active and selective photosensitizers.

Preparation of radiolabeled erlotinib analogues and analysis of the effect of linkers

Erlotinib is a first generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which was granted Food and Drug administration (FDA) approval for treatment of patients with locally advanced or metastatic NSCLC. The present study aimed at development of radiolabeled erlotinib variants as tyrosine kinase inhibitors. Three DOTA-erlotinib conjugates were prepared for radiolabeling with 177Lu. The terminal alkyne group of erlotinib was modified by performing Cu-catalyzed click chemistry and three different linkers were introduced which were then conjugated to the chelator, DOTA. The DOTA-erlotinib conjugates were characterized by 1H NMR and ESI-MS. 177Lu-DOTA-erlotinib complexes were characterized using natLu-DOTA-erlotinib conjugates. The 177Lu-complexes exhibited high in vitro stability in human serum up to 48 h. They were highly hydrophilic in nature as observed from their log Po/w values (177Lu-DOTA-propyl-Er: −2.5 ± 0.1; 177Lu-DOTA-PEG3-Er: −3.0 ± 0.1; 177Lu-DOTA-PEG6-Er: −3.3 ± 0.1). The MTT assay in A431 human epidermoid carcinoma cell lines indicates that the chemical modification at the terminal alkyne group of the erlotinib molecule does not have significant effect on its TKI property. Biodistribution studies in normal Swiss mice demonstrated fast clearance and excretion of 177Lu-labeled erlotinib complexes. These studies indicate that erlotinib variants with hydrophobic pharmacokinetic modifiers/chelators may enhance the retention of 177Lu-labeled complexes in blood thereby increasing the probability to reach EGFR-expressing tumor.

Chemical Characteristics of Ethanol and Water Extracts of Black Alder (Alnus glutinosa L.) Acorns and Their Antibacterial, Anti-Fungal and Antitumor Properties.

The aim of this study was to identify polyphenolic compounds contained in ethanol and water extracts of black alder (Alnus glutinosa L.) acorns and evaluate their anti-cancer and antimicrobial effects. The significant anti-cancer potential on the human skin epidermoid carcinoma cell line A431 and the human epithelial cell line A549 derived from lung carcinoma tissue was observed. Aqueous and ethanolic extracts of alder acorns inhibited the growth of mainly Gram-positive microorganisms (Staphylococcus aureus, Bacillus subtilis, Streptococcus mutans) and yeast-like fungi (Candida albicans, Candida glabrata), as well as Gram-negative (Escherichia coli, Citrobacter freundii, Proteus mirabilis, Pseudomonas aeruginosa) strains. The identification of polyphenols was carried out using an ACQUITY UPLC-PDA-MS system. The extracts were composed of 29 compounds belonging to phenolic acids, flavonols, ellagitannins and ellagic acid derivatives. Ellagitannins were identified as the predominant phenolics in ethanol and aqueous extract (2171.90 and 1593.13 mg/100 g DM, respectively) The results may explain the use of A. glutinosa extracts in folk medicine.

Anticancer and Free Radical Scavenging Competence of Zinc Oxide Nanoparticles Synthesized by Aqueous Leaf Extract of Phyllanthus acidus.

The purpose of this study was aimed to investigate the zinc oxide nanoparticles (ZnONPs) synthesizing efficiency of aqueous leaf extract of Phyllanthus acidus. Furthermore, the antioxidant and anticancer activities of synthesized ZnONPs were also investigated through the in-vitro approach. The obtained results show that the aqueous extract of P. acidus can synthesize ZnONPs, as evidenced by a sharp absorbance peak at 375 nm. The Fourier transform infrared spectroscopy (FTIR) analysis confirmed that the aqueous extract contained significant numbers of functional groups, which were involved in reducing zinc nitrate into ZnONPs. Also, they participate in the capping and stabilization of synthesized ZnONPs and their size ranged from 27.14-35.74 nm with a spherical shape . The results obtained in ABTS radical scavenging activity 1, 1-diphenyl-2-picryl-hydroxyl (DPPH), hydrogen peroxide (H2O2), and 2,2'-Azino-Bis(3-ethylbenzene thiazoline-6-sulfonic acid) (ABTS) assays declared has excellent in-vitro radicals scavenging activity with reasonable IC50 values. Interestingly, these green synthesized ZnONPs have an excellent anticancer activity against human epidermoid carcinoma (Hep3) cell line in an in-vitro approach. These findings imply that an aqueous leaf extract of P. acidus can be used to synthesize pharmaceutically valuable ZnONPs. To consider such nanomaterials as potential therapeutic agents, optimization and in-vivo biomedical studies are required.

Cytotoxic effects of water and ethanolic extracts of Turkish propolis on human laryngeal epidermoid carcinoma cell lines

Propolis is a natural resinous substance collected by bees from various types of trees and plants and has antibacterial, antiviral and antitumoral features depending on its antioxidant properties. Major aim is to investigate cytotoxic effect of Turkish propolis on human laryngeal epidermoid carcinoma (HEp-2) cells. HEp-2 cells/well were loaded on RTCA(real time cell analysis) system and the cell index was followed up during 48 hours. Water extract of Turkish propolis (WEP) of 250-10.000 μg/mL concentrations and ethanolic extracts of Turkish propolis (EEP) of 10-2.400 μg/mL concentrations were treated with HEp-2 cells and followed by RTCA system. The cell indexes and IC50 values were determined. HEp-2 cells were incubated with WEP and EEP. Proliferation was followed by flow cytometric DNA cycle analysis. WEP and EEP were found to be cytotoxic to HEp-2 cells. When WEP and EEP were incubated with HEp-2 cells during 72 hours, the highest antiproliferative effect was seen by interfering DNA cycles. Turkish propolis extracts were found to be cytotoxic and antiproliferative to HEp- 2 cells in the present study, therefore, it was concluded that it may fall within chemotherapy or target therapies for larynx cancers.

Chemical profiling and cytotoxic activity of aqueous extract of Veronica peduncularis M.Bieb.: A chemotaxonomical approach

Background and Aims: Genus Veronica (Plantaginaceae) is represented by 79 species in Turkish flora, 26 of which are endemic. Veronica species have a variety of uses including diuretic, anticancer, and rheumatic pains, wounds, and respiratory problems. According to phytochemical studies, Veronica species contain predominantly iridoid glucosides with some phenylethanoid and flavonoid glycosides. Methods: The aqueous extract of Veronica peduncularis M.Bieb. was tested for its cytotoxic activity on human rhabdomyosarcoma (RD) and human epidermoid carcinoma (HEp-2) cell lines using the MTT method. Chemical profile of the extract was determined by HPLC-DAD, and isolation studies were conducted. Results: The extract was found to show concentration-dependent cytotoxicity against tested cell lines. In addition, a comparison of the iridoid fraction of Veronica peduncularis with previously isolated iridoid glucosides on the HPLC-DAD system, showed the presence of aucubin, amphicoside, veratroyl catalpol, and veronicoside in this fraction. On the other hand, isolation and structure elucidation of plantamajoside and 4'-O-methylisoscutellarein-7-O-2''-O-(6'''-O-acetyl-ß-D-allopyranosyl)- ß-D-glucopyranoside from the phenolic fractions were performed by serial chromatographic and spectroscopic methods. Conclusion: To the best of our knowledge, this is the first cytotoxic activity and phytochemical study on the titled plant. The presence of iridoid glucosides and 8-hydroxyflavone glycosides is important for the chemotaxonomy of the genus Veronica.

Cytotoxic and antibacterial depsidones from the endophytic fungus Chaetomium brasiliense isolated from Thai rice

Four new depsidones, mollicellins V-Y (1-4), together with eight known depsidones (5-12) were isolated from the endophytic fungus, Chaetomium brasiliense, detached from stems of Thai rice. Their structures were determined by extensive spectroscopic methods. Mollicellins X, H, and F (3, 8 and 10) showed potent cytotoxicity against the human oral epidermoid carcinoma (KB) cell line, and mollicellin F (10) also showed a potent cytotoxicity against the human hepatocellular carcinoma (HepG2) cell line. Besides, mollicellin B (11) exhibited cytotoxicity against the colorectal adenocarcinoma (HT-29) cell line. Moreover, most of the isolated depsidones displayed potent antibacterial activity against Gram-positive bacteria, Bacillus cereus and Bacillus subtilis, and several of them showed moderate activity against Methicillin-resistant Staphylococcus aureus (MRSA) and clinical isolates of S. aureus. In addition, a few of them also showed moderate activity against a Gram-negative bacteria Pseudomonas aeruginosa.

Halofuginone enhances the anti-tumor effect of ALA-PDT by suppressing NRF2 signaling in cSCC

Background5-aminolevulinic acid-mediated PDT (ALA-PDT) has been used in a variety of skin diseases including cSCC (cutaneous squamous cell carcinoma). Halofuginone (HL) is a less-toxic febrifugine derivative and has inhibitory effects on a variety of cancer cells. For now, there are no published study focusing on the combination use of ALA-PDT with HL to improve clinical efficacy of cSCC. ObjectiveIn this study, we will examine the effectiveness of combined treatment of ALA-PDT and HL in cSCC as well as its underlying mechanism. MethodsThe human epidermoid carcinoma cell line SCL-1 was treated with ALA-PDT or/ and HL, and cell viability, cell migration, ROS production, apoptosis were evaluated by CCK-8, colony formation, scratch assay, DCFH-DA probe, flow cytometry, respectively. The protein expression of NRF2 signaling was examined by western blot. ResultsHL strengthened ALA-PDT's inhibition of SCL-1 cell viability, migration, as well as NRF2 related β-catenin, p-Erk1/2, p-Akt and p-S6K1 expression. Overexpression of NRF2 conferred resistance to co-treatment's effects on c-Myc, Cyclin D1, Bcl-2, as well as cell proliferation. HL also strengthened ALA-PDT's inhibition of tumor volume in cSCC mouse model and elevated ROS generation of ALA-PDT. ConclusionHL enhances the anti-tumor effect of ALA-PDT in vitro and in vivo. HL has the potential to enhance the anti-tumor effect of ALA-PDT in cSCC via inhibiting NRF2 signaling.

Investigation of 3-sulfamoyl coumarins against cancer-related IX and XII isoforms of human carbonic anhydrase as well as cancer cells leads to the discovery of 2-oxo-2H-benzo[h]chromene-3-sulfonamide - A new caspase-activating proapoptotic agent.

Herein we report the synthesis of a set of seventeen 3-sulfonamide substituted coumarin derivatives. Prepared compounds were tested invitro for inhibition of four physiologically relevant isoforms of the metalloenzyme human carbonic anhydrase (hCA, EC 4.2.1.1). Several coumarin sulfonamides displayed low nanomolar KI values against therapeutically relevant hCA II, IX, and XII, whereas they did not potently inhibit hCA I. Some of these compounds exerted a concentration-dependent antiproliferative action toward RT4 human bladder cancer and especially A431 human epidermoid carcinoma cell lines. In the meantime, the viability of non-tumorigenic hTERT immortalized human foreskin fibroblast cell line Bj-5ta was not significantly affected by the obtained derivatives. Interestingly, compound 10q (2-oxo-2H-benzo [h]chromene-3-sulfonamide) showed a profound and selective dose-dependent inhibition of A431cell growth with low nanomolar IC50 values. We demonstrated that 10q possessed a concentration-dependent apoptosis induction activity associated with caspase 3/7 activation in cancer cells. As carbonic anhydrase isoforms in question were not potently inhibited by this compound, its antiproliferative effects likely involve other mechanisms, such as DNA intercalation. Compound 10q clearly represents a viable lead for further development of new-generation anticancer agents.

Assessment of antinuclear antibodies (ANA): National recommendations on behalf of the Croatian society of medical biochemistry and laboratory medicine.

Antinuclear antibodies (ANA) represent a family of autoantibodies targeting ubiquitous cellular constituents and are a hallmark of systemic inflammatory autoimmune rheumatic diseases named connective tissue diseases (CTD). The gold standard method for ANA determination is indirect immunofluorescence (IIF) on the human laryngeal epidermoid carcinoma cell line type 2 substrate (HEp-2), but with increasing demand for ANA testing, novel methods eased for automation emerged, which allows testing by staff less experienced in this specific field of laboratory diagnostic. In 2016 The working group (WG) for laboratory diagnostics of autoimmune diseases as part of the Committee for the Scientific Professional Development of the Croatian Society of Medical Biochemistry and Laboratory Medicine (CSMBLM) published the data of a survey regarding general practice in laboratory diagnostics of autoimmune diseases in Croatia. Results indicated high diversity in the performance of autoantibody testing as well as reporting of the results and indicated the need of creating recommendations for the assessment of ANA that would help harmonize diagnostics of systemic autoimmune rheumatic diseases in Croatia. This document encompasses twenty-seven recommendations for ANA testing created concerning indications for ANA testing, preanalytical, analytical, and postanalytical issues, including rational algorithm and quality control assurance. These recommendations are based on the relevant international recommendations and guidelines for the assessment of ANA testing and relevant literature search and should help to harmonize the approach in ANA testing and clarify differences in interpretation of the results obtained using different methods of determination.

Costunolide, a Sesquiterpene Lactone, Suppresses Skin Cancer via Induction of Apoptosis and Blockage of Cell Proliferation.

Costunolide is a naturally occurring sesquiterpene lactone that demonstrates various therapeutic actions such as anti-oxidative, anti-inflammatory, and anti-cancer properties. Costunolide has recently emerged as a potential anti-cancer agent in various types of cancer, including colon, lung, and breast cancer. However, its mode of action in skin cancer remains unclear. To determine the anti-cancer potential of costunolide in skin cancer, human epidermoid carcinoma cell line A431 was treated with costunolide. A lactate dehydrogenase assay showed that costunolide diminished the viability of A431 cells. Apoptotic cells were detected by annexin V/propidium iodide double staining and Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling assay assay, and costunolide induced cell apoptosis via activation of caspase-3 as well as induction of poly-ADP ribose polymerase cleavage in A431 cells. In addition, costunolide elevated the level of the pro-apoptotic protein Bax while lowering the levels of anti-apoptotic proteins, including Bcl-2 and Bcl-xL. To address the inhibitory effect of costunolide on cell proliferation and survival, various signaling pathways, including mitogen-activated protein kinases, signal transducer and activator of transcription 3 (STAT3), nuclear factor κB (NF-κB), and Akt, were investigated. Costunolide activated the p38 and c-Jun N-terminal kinase pathways while suppressing the extracellular signal-regulated kinase (ERK), STAT3, NF-κB, and Akt pathways in A431 cells. Consequently, it was inferred that costunolide suppresses cell proliferation and survival via these signaling pathways. Taken together, our data clearly indicated that costunolide exerts anti-cancer activity in A431 cells by suppressing cell growth via inhibition of proliferation and promotion of apoptosis. Therefore, it may be employed as a potentially tumor-specific candidate in skin cancer treatment.

Synthesis, Characterization, Antimicrobial and Anticancer Activity of New Bidentate Schiff Base Ligand and their Transition Metal(II) Complexes

The metal(II) complexes were synthesized by addition of corresponding MCl2 (M = Mn2+, Ni2+, Cu2+ and Zn2+) with 1,2-bis(1H-pyrrol-2-ylmethylene)diazane in methanol. The ligand acts as a bidentate as confirmed from the mass, IR, UV, NMR and EPR spectral studies. The Schiff base ligand forms hexa-coordinated complexes having octahedral geometry for Mn(II), Ni(II), Zn(II) and Cu(II) complexes. The metal complexes showed an excellent antimicrobial activity spectrum in vitro against both Gram-negative (Klebsiella pneumoniae and Acinetobacter baumannii), Gram-positive (Staphylococcus aureus and Enterococcus faecalis) and human pathogenic bacteria isolates. To find the binding affinity with protein BSA kinase, for that molecular docking studies were also carried for all the four synthesized metal(II) complexes. The anticancer activity of the synthesized metal(II) complexes was also screened against the three human tumor cell lines MCF7 human breast adenocarcinoma cell line, CaSki human caucasian cervical epidermoid carcinoma and HCT116 human colon cancer cell lines. The present study showed that Zn(II) complex showed potent inhibition by the ratio of 80% as compared to the inhibition in the normal cells (L-6).

Topical nanostructured lipid carrier gel of quercetin and resveratrol: Formulation, optimization, in vitro and ex vivo study for the treatment of skin cancer.

The objective of this investigation was to develop dual drug-loaded nanostructured lipid carrier (NLC) gel of quercetin and resveratrol to enhance their disposition in dermal and epidermal layers. The optimization of the lipidic phase, i.e., liquid lipid and solid lipid was done on the basis of the solubility of quercetin & resveratrol in lipids in the preformulation stage. NLC formulation was optimized by central composite rotatable design (CCRD). The NLC formulation contained lipid binary mixture (1.0% w/w) and Cremophor RH40 (5% w/v) as a surfactant and had a particle size of 191nm±5.20, polydispersity index (PDI) of 0.33±0.01, zeta potential (ZP) of -10.00mV±0.30 and entrapment efficiency (EE) of 92.85±0.25% (quercetin), 89.05±0.18% (resveratrol) respectively. The flux and permeability coefficient of quercetin and resveratrol from NLC gel were found to be 14.09µg/cm2/h, 3.70µg/cm2/h and 7.21×10-2cm/h, 4.69×10-2cm/h respectively. Dermatokinetic studies revealed that there was a significant increase in the CSkin max and AUC0-8h in skin treated with NLC gel as compared to skin treated with conventional gel, which was prepared using carbopol 934 (1.5% w/w). Further, all claims of dermatokinetic studies were proved by confocal microscopic (CLMS) studies, which revealed that the disposition of combinatorial NLC gel was higher (~3 folds) as compared to the conventional gel. Furthermore, skin treated with NLC gel and untreated skin were analysed by FTIR and DSC spectra to understand the permeation dynamics of NLC gel. The cytotoxic effect of combinatorial NLC gel and the conventional gel assessed in human epidermoid carcinoma (A431) cell line by MTT assay, revealed that IC50 of NLC gel and the conventional gel was 86.50µM and 123.64µM respectively. Thus, these results disclosed that NLC gel could be used as a potential carrier for the delivery of quercetin & resveratrol into deeper layers of the skin and can serve as a promising formulation for treatment of skin cancer.

Low-frequency mechanical vibration induces apoptosis of A431 epidermoid carcinoma cells.

Cancer research is increasingly focused on discovering strategies to induce cancer cell apoptosis without affecting surrounding normal cells. One potential biocompatible method is mechanical vibration, which has been developed as part of the emerging field of mechanomedicine. Previous studies of mechanical vibration have employed high‐frequency vibration, which damages healthy cells. In this study, we examined the effects of brief (1 h) low‐frequency (20 Hz) mechanical vibration on glucose consumption and survival (apoptosis, necrosis, HMGB1 release) of the human epidermoid carcinoma cell line A431. We found that apoptosis, but not necrosis, was significantly increased at 48 h after mechanical vibration compared with cells maintained in static culture. In keeping with this, extracellular release of HMGB1, a necrosis marker, was lower in cultures of A431 cells subjected to mechanical vibration compared with control cells. Glucose consumption was increased in the first 24 h after mechanical vibration but returned to control levels before the onset of apoptosis. Although the precise intracellular mechanisms by which low‐frequency mechanical vibration triggers apoptosis of A431 cells is unknown, these results suggest a possible role for metabolic pathways. Mechanical vibration may thus represent a novel application of mechanomedicine to cancer therapy.