Epidermoid Carcinoma Cells Research Articles

Design, synthesis, and biological evaluation of hederagenin derivatives with improved aqueous solubility and tumor resistance reversal activity.

Multidrug resistance (MDR) has become a major obstacle to malignancies treatment by chemotherapeutic drugs, therefore, it is important to develop MDR reversal agents with high activity. We have previously found that the hederagenin (HD) derivative HBQ showed good tumor MDR reversal activity invitro and invivo but had poor solubility. In this study, to enhance the aqueous solubility and tumor MDR reversal activity of HBQ, three series of HD derivatives were designed and synthesized. Nitrogen-containing heterocyclic-substituted, PEGylated, and ring-A substituted derivatives significantly reversed the MDR phenotype of KBV (multidrug-resistant oral epidermoid carcinoma) cells toward paclitaxel at a concentration of 10μM in MTT assays. The PEGylated derivatives 10c-10e had increased aqueous solubility compared with HBQ by 18-657 fold, while maintaining tumor MDR reversal activity. The most invitro active compound 10c possessed good chemical stability to an esterase over 24h and enhanced the sensitivity of KBV cells to paclitaxel and vincristine with IC50 values of 4.58 and 0.79nM, respectively. Mechanism studies indicated that compound 10c increased the accumulation of P-glycoprotein (P-gp) substrates rhodamine 123 and Flutax1 in KBV cells and MCF-7T (paclitaxel-resistant breast carcinoma) cells, that is to say, compound 10c exerted the reversal effect of tumor MDR by inhibiting the efflux function of P-gp. Finally, the structure-activity relationships were further investigated by analyzing the relationship between structure and tumor MDR reversal activity of HD derivatives. This study highlights the potential of PEGylated HD derivatives such as compound 10c for the development of tumor MDR reversal agents and provides information for the further improvement of the aqueous solubility and tumor MDR reversal activity of HD derivatives in the future.

Verbascum nigrum: Cytotoxicity Evaluation in A431 Epidermoid Carcinoma Cells and Untargeted LC-HR-MS/MS Metabolite Profiling.

The crude methanolic extract obtained from Verbascum nigrum aerial parts (VNE) and its six fractions (VNF1-VNF6) were initially screened regarding their effects on the viability of immortalized HaCaT keratinocytes and A431 epidermoid carcinoma cells (MTT assay, 24 h). None of the tested samples affected the viability of HaCaT cells in a concentration range of 25-150 μg/mL. VNE and VNF4 exhibited significant cytotoxic effects in A431 cells, with IC50 values of 81.92 and 12.27 μg/mL, respectively; the selectivity index was higher than 10 for VNF4. The untargeted LC/HR-MS/MS metabolite profiling led to the tentative annotation of a total number of 23 compounds. Of these, VNE comprised mainly iridoid glycosides (harpagoside, laterioside, acylated aucubin derivatives), whereas VNF4 showed a high abundance of triterpene saponin glycosides (ilwensisaponins A and C, songarosaponins A and B), constituents known for their selective cytotoxic potential.

The otc gene of Streptococcus suis plays an important role in biofilm formation, adhesion, and virulence in a murine model

Streptococcus suis (S. suis) is an emerging zoonotic pathogen that can cause meningitis, arthritis, pneumonia, and sepsis. It poses a serious threat to the swine industry and public health worldwide. Ornithine carbamoyltransferase (OTC) is involved in the arginine deiminase system. OTC, which is a widely distributed enzyme in microorganisms, mammals, and higher plants, catalyzes the conversion of ornithine to citrulline. The present study showed that the otc gene plays an important role in the pathogenesis of S. suis infections. The ability of an otc-deficient mutant (Δotc) to form a biofilm was significantly reduced compared to the wild-type (WT) strain, as determined by crystal violet staining. Confocal laser scanning microscopy and scanning electron microscopy observations showed that the weakening of biofilm formation by the Δotc strain is related to a decrease in the extracellular matrix. In addition, compared to the WT strain, the Δotc strain had a reduced capacity to adhere to human laryngeal epidermoid carcinoma (HEp-2) cells compared to the WT strain. A real-time PCR analysis showed that the expression of adhesion-related genes by the Δotc strain was also lower than that of the WT strain. The virulence of the Δotc strain was significantly lower than that of the WT strain in a murine infection model. In addition, a histological analysis showed that the pathogenicity of the Δotc strain was lower than that of the WT strain, causing only slight inflammatory lesions in lung, liver, spleen, and kidney tissues. No significant differences were observed between the complemented mutant (CΔotc) and WT strains with respect to biofilm formation, adhesion, gene expression, and virulence. The present study provided evidence that the otc gene plays a pivotal role in the regulation of S. suis adhesion and biofilm formation. It also suggested that the otc gene is indirectly involved in the pathogenesis of S. suis serotype 2 infections.

53P Light-driven photoswitching of novel combretastatin A-4 analogues: Therapeutic targeting of epidermoid carcinoma cells

53P Light-driven photoswitching of novel combretastatin A-4 analogues: Therapeutic targeting of epidermoid carcinoma cells

Metabolic profile and skin-related bioactivities of Cerioporus squamosus hydromethanolic extract

Abstract. Elkhateeb WA, Daba GM, Elnahas MO, Thomas PW, Emam M. 2020. Metabolic profile and skin-related bioactivities of Cerioporus squamosus hydromethanolic extract. Biodiversitas 21: 4732-4740. Being a functional food capable of showing nutritional as well as medicinal properties have great attention. Mushrooms have been proven as leading targets in this field. For this purpose, the edible mushroom Cerioporus squamosus was investigated in this study to evaluate the in vitro skin-related bioactivities of its hydromethanolic extract in terms of enhancing wound healing, and human skin cancer suppression capabilities. Treatment of fibroblast cells (BJ-1) with the hydromethanolic extract of this mushroom at 50 µg/mL enhanced cell migration rates by 71.7% after 24 h of exposure to the extract. Moreover, the same extract exhibited a promising impact on human skin cancer using an epidermoid carcinoma cell line (A431). The gradual increase in C. squamosus hydromethanolic extract concentration caused gradual decrease in the A431 cell viability and proliferation. Maximum effect on reducing the cell viability was obtained at a concentration of 100 µg/mL, where cell viability was 3.7%, and recorded IC50 was 52.6 µg/mL. The metabolic profile of the extract was analyzed by GC-MS, which was performed on its silylated metabolites. Nineteen compounds were detected including sugar alcohols, amino acids, fatty and organic acids. Promising results of this mushroom extract encourage conducting further steps towards using this mushroom as a functional food showing promising bioactivities.

Zinc Oxide Nanoparticle Induces Apoptosis in Human Epidermoid Carcinoma Cells Through Reactive Oxygen Species and DNA Degradation.

Zinc oxide nanoparticles (ZnO-NPs) are used immensely in technology and medicine, but very less is known about toxicity mechanism to human epidermal cells. The objective of this study was to evaluate possible anticancer properties of ZnO-NPs on human epidermoid carcinoma cells using MTT assay, measurement of reactive oxygen species, DNA fragmentation, and nuclear condensation. ZnO-NPs were synthesized by sol-gel method using zinc acetate dihydrate, ethylene glycol, and 2-propyl alcohol. Numerous characterization techniques such as UV-visible spectroscopy, X-ray powder diffraction, transmission electron microscopy, and dynamic light scattering spectroscopy were used to confirm synthesis, purity, optical, and surface characteristics, size, shape, and distribution of ZnO-NPs. Our finding showed that ZnO-NPs considerably decreased cell viability of human epidermoid carcinoma A431 cells with a parallel increase in nuclear condensation and DNA fragmentation in a dose dependent manner. Moreover, real time PCR expression study showed that treatment of human epidermoid carcinoma cells with ZnO-NPs trigger increased expression of tumor suppressor gene p53, bax, and caspase-3 while downregulate antiapoptotic gene bcl-2. Thus ZnO-NPs induce apoptosis in A431 cells through DNA degradation and generation of reactive oxygen species via p53, bax/bcl-2, and caspase pathways.

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.

The Role of miR-143, miR-145, and miR-590 in Expression Levels of CD44 and Vascular Endothelial Cadherin in Oral Squamous Cell Carcinoma

Background: Oral squamous cell carcinoma (OSCC) is the most common head and neck cancer with a continuing rise of incidence in developing countries. Despite the improvement in the clinical outcome of OSCC, the overall 5-year survival rate of patients is still disappointing. MicroRNAs (miRNAs) regulate gene expression in the post-transcriptional stage by targeting mRNAs. Advances in knowledge of the pathogenesis and molecular events lead to the improvement of OSCC treatments. Materials and Methods: Human oral epidermoid carcinoma cells (KB), HGF1, and HEK 293T cell line were cultured. Lentiviral vectors were constructed and Western Blot analysis was performed. Then, immunocytochemistry staining was performed by using CD44 and vascular endothelial cadherin (VE-Cadherin) antibodies. All data were analyzed using the REST 2009 software. P values of ≤0.05 were considered statistically significant. Results: MiR-143, miR-145, and miR 590 were down-regulated in the oral cancer cell line. Following transfection of Lv miR 143, Lv-miR-145, and Lv-miR-590, the expression of CD44 was markedly decreased in KB cells. In addition, transfection of miR-143 and miR- 590 mimics into the oral cancer cell line significantly decreased the expresion level of VE-Cadherin; however, transfection of miR-145 mimic had no significant effect on the expression of VE-Cadherin. Western blot analysis and immunocytochemistry staining confirmed the results. Conclusion: This study revealed that miR-143, miR-145, and miR-590 negatively regulate CD44 and VE-Cadherin (except miR-145) expression, which might play a crucial role in the induction of cancer stem cells proliferation and angiogenesis in OSCC cells. The knowledge about the involved factors may provide new insights for the clinical use of miR- 143, mR-145, and miR-590 in the treatment of patients with OSCC.

Synthesis, Cytotoxic Activity and Molecular Docking Studies of New Condensed Thieno[2,3-d]Pyrimidines as Antitumor Agents

A series of twenty molecules based on thienopyrimidine nucleus fused with 5-, 6-, and 7-membered lactam rings as well as triazole were synthesized via 4-step reactions. The target compounds were obtained in good yield and confirmed for their structural integrity. The cytotoxic activity against A431 human epidermoid carcinoma and H9c2 rat cardiomyocyte cells were studied by MTT assay. Most of the synthesized compounds except 8a showed 85% cell death in both human A341 and rat H9c2 cell lines, indicating potential anticancer activity of these compounds. Interestingly, compound 8a showed a reversal in trend by enhancing the growth of both A341 and H9c2 cells.

ALOX12B promotes carcinogenesis in cervical cancer by regulating the PI3K/ERK1 signaling pathway.

Cervical cancer is a malignant disease and a threat to women's health worldwide. Surgical resection followed by radiotherapy or chemotherapy is the main treatment strategy for cervical cancer; however, patients with cervical cancer, especially those with late-stage disease, may not benefit from these traditional therapies, which results in poor clinical outcome. ALOX12B is a gene encoding lipoxygenase, and a mutation in ALOX12B was detected in lung and breast cancer. Furthermore, ALOX12B is essential to the proliferation of epidermoid carcinoma cells; however, the role of ALOX12B in cervical cancer has not been studied thus far, to the best of our knowledge. In the present study, the expression levels of ALOX12B were reduced in cervical cancer cells by lentiviral transfection, and it was found that both cell proliferation and clone formation ability were significantly reduced, and the cell cycle was blocked at G1 phase. Tumor growth was also suppressed in vivo in a xenograft tumor model, but the migration of tumor cells was not affected by ALOX12B. Subsequently, using western blotting, it was demonstrated that knockdown of ALOX12B decreased the expression levels of PI3K, MEK1, ERK1, C-fos and cdc25. Meanwhile, overexpression of ALOX12B increased the expression levels of these five molecules. Conclusively, ALOX12B promoted cell proliferation in cervical cancer via regulation of the PI3K/ERK1 signaling pathway. The present study may improve our understanding of the molecular mechanisms underlying the function of ALOX12B in cervical cancer and inform new therapeutic strategies.

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.

Targeted Delivery of 111In Into the Nuclei of EGFR Overexpressing Cells via Modular Nanotransporters With Anti-EGFR Affibody.

Since cell nucleus is one of the most vulnerable compartments, the maximum therapeutic effect from a variety of locally acting agents, such as photosensitizers, alfa-emitters, Auger electron emitters, will be expected when they get there. Therefore, the targeted delivery of these agents into the nuclei of target tumor cells is necessary for their anticancer effects and minimization of side effects. Modular nanotransporters (MNT) are artificial polypeptides comprising several predefined modules that recognize target cell, launching their subsequent internalization, escape from endosomes, and transport the drug load to the nucleus. This technology significantly enhances the cytotoxicity of locally acting drugs in vitro and in vivo. Epidermal growth factor receptors (EGFR) are useful molecular targets as they are overexpressed in glioblastoma, head-and-neck cancer, bladder cancer, and other malignancies. Here, we examined the possibility of using internalizable anti-EGFR affibody as an EGFR-targeting MNT module for drug transport into the cancer cell nuclei. It binds to both murine and human EGFR facilitating preclinical studies. We showed that MNT with affibody on the N-terminus (MNTN-affibody) effectively delivered the Auger electron emitter 111In to target cell nuclei and had pronounced cytotoxic efficacy against EGFR-overexpressing human A431 epidermoid carcinoma cells. Using EGFR-expressing human adenocarcinoma MCF-7 cells, we demonstrated that in contrast to MNT with N-terminal epidermal growth factor (EGF), MNTN-affibody and MNT with EGF on the C-terminus did not stimulate cancer cell proliferation.

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.

Escherichia coli-based synthesis of cadmium sulfide nanoparticles, characterization, antimicrobial and cytotoxicity studies.

The present research describes the synthesis of cadmium sulfide (CdS) nanoparticles from Escherichia coli under the influence of bacterial enzyme sulphate reductase and study on their cytotoxicity for applications in cancer therapy. Escherichia coli cells were used to synthesize CdS nanoparticles under different concentrations of cadmium chloride and sodium sulfide. The morphology of the nanoparticles was analysed using scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDX) was used for elemental analysis of nanoparticles. Fourier-transform infrared spectroscopy analysis (FTIR) was performed to assess the functional groups of the nanoparticles. Crystalline nature of nanoparticles was assessed using powder X-ray diffraction (XRD). Antibacterial studies of CdS nanoparticles were carried out on foodborne pathogens and cytotoxicity studies were carried out on Mus musculus skin melanoma (B16F10) and human epidermoid carcinoma (A431) cell lines. CdS nanoparticle showed more cytotoxic effect on cancer cells compared with standard 5-aminolevulinic acid (5-ALA). The Escherichia coli-synthesized CdS nanoparticles showed highest zone of inhibition in the ratio 4:1 of cadmium chloride and sodium sulfide on all tested bacterial strains. The nanoparticles were also tested for haemolytic activity on RBC cells, which exhibited lower cytotoxicity than sodium dodecyl sulphate which was used as positive control. The cytotoxicity of CdS nanoparticles assessed on A431 cells showed an inhibition of 81.53% at 100μM concentration while the cytotoxicity assessed on B16F10 cells showed an inhibition of 75.71% at 200μM concentration which was much efficient than 5-ALA which showed an inhibition of 31.95% at a concentration against B16F10 cells and 33.45% against A431 cells at a concentration of 1mM. Cadmium sulfide nanoparticles were thus found to be highly toxic on cancer cells compare with standard anticancerous drug 5-ALA.

Pegylated carbon nitride nanosheets for enhanced reactive oxygen species generation and photodynamic therapy under hypoxic conditions

The application of photodynamic therapy (PDT) is of ever-increasing importance in the treatment of malignant tumors; however, there are several major constraints that make it impossible to achieve optimal therapeutic effects. Our objective is to develop a novel photosensitizing drug for skin cancer. In the experiment, we fabricated four-arm-poly ethylene glycol modified amino-rich graphite phase carbon nitride nanosheets (AGCN-PEG), which have good stability in physiological solution and show selective accumulation in tumor cells. Under hypoxic conditions, the AGCN-PEG induced PDT can effectively inhibit growth on A431 human epidermoid carcinoma cells in vivo and in vitro. What's more, after being combined with TMPyP4, the therapeutic effect of AGCN-PEG was greatly improved.

The PI3K subunits, P110\u03b1 and P110\u03b2 are potential targets for overcoming P-gp and BCRP-mediated MDR in cancer

BackgroundPI3K/AKT is a vital signaling pathway in humans. Recently, several PI3K/AKT inhibitors were reported to have the ability to reverse cancer multidrug resistance (MDR); however, specific targets in the PI3K/AKT pathways and the mechanisms associated with MDR have not been found because many of the inhibitors have multiple targets within a large candidate protein pool. AKT activation is one presumed mechanism by which MDR develops during cancer treatment.MethodsThe effects of inhibiting PI3K 110α and 110β by BAY-1082439 treatment and CRISPR/Cas9 knockout were examined to determine the possible functions of BAY-1082439 and the roles of PI3K 110α and 110β in the reversal of MDR that is mediated by the downregulation of P-gp and BCRP. Inhibition of AKT with GSK-2110183 showed that the downregulation of P-gp and BCRP is independent of generalized AKT inactivation. Immunofluorescence, immunoprecipitation, MTT, flow cytometry and JC-1 staining analyses were conducted to study the reversal of MDR that is mediated by P-gp and BCRP in cancer cells. An ATPase assay and a structural analysis were also used to analyze the potential mechanisms by which BAY-1082439 specifically targets PI3K 110α and 110β and nonspecifically influences P-gp and BCRP.ResultsBy inhibiting the activation of the PI3K 110α and 110β catalytic subunits through both the administration of BAY-1082439 and the CRISPR/Cas9 deletion of Pik3ca and Pik3cb, the ATP-binding cassette transporters P-gp/ABCB1 and BCRP/ABCG2 were downregulated, thereby reestablishing the drug sensitivity of human epidermoid carcinoma and non-small cell lung cancer (NSCLC) MDR cells. Inhibition of AKT did not reverse the MDR mediated by P-gp or BCRP. The ABC family proteins and AKT may play MDR-enhancing roles independently.ConclusionsThe reversal of the dual functions of ABC-transporter-mediated and AKT-activation-enhanced MDR through the inhibition or knockout of PI3K 110α or 110β promises to improve current strategies based on combined drug treatments to overcome MDR challenges.

Enhanced anti-tumor efficacy of 5-aminolevulinic acid-gold nanoparticles-mediated photodynamic therapy in cutaneous squamous cell carcinoma cells.

The objective of this study was to investigate whether the conjugation of gold nanoparticles (GNPs) to 5-aminolevulinic acid (5-ALA) could enhance the anti-tumor efficiency of photodynamic therapy (PDT) in epidermoid carcinoma cells. The mRNA and protein expression levels were determined by quantitative real-time PCR and western blot, respectively. Cell viability, apoptosis, invasion, and migration were determined by MTT assay, flow cytometry, transwell invasion assay, and migration assay, respectively. Singlet oxygen generation was detected by the singlet oxygen sensor green reagent assay. Our results showed that PDT with 5-ALA and GNPs-conjugated 5-ALA (5-ALA-GNPs) significantly suppressed cell viability, increased cell apoptosis and singlet oxygen generation in both HaCat and A431 cells, and PDT with 5-ALA and 5-ALA-GNPs had more profound effects in A431 cells than that in HaCat cells. More importantly, 5-ALA-GNPs treatment potentiated the effects of PDT on cell viability, cell apoptosis, and singlet oxygen generation in A431 cells compared to 5-ALA treatment. Further in vitro assays showed that PDT with 5-ALA-GNPs significantly decreased expression of STAT3 and Bcl-2 and increased expression of Bax in A431 cells compared with PDT with 5-ALA. In addition, 5-ALA-GNPs treatment enhanced the inhibitory effects of PDT on cell invasion and migration and Wnt/β-catenin signaling activities in A431 cells compared to 5-ALA treatment. In conclusion, our results suggested that GNPs conjugated to 5-ALA significantly enhanced the anti-tumor efficacy of PDT in A431 cells, which may represent a better strategy to improve the outcomes of patients with cutaneous squamous cell carcinoma.

Synthesis and antitumor activities investigation of a C-nucleoside analogue of ribavirin

SRO-91 is a non-natural ribofuranosyl-1,2,3-triazole C-nucleoside obtained by a synthetic sequence involving a C-alkynyl glycosylation mediated by metallic indium and a Huisgen cycloaddition for the construction of the triazole. Its structure is close to the one of ribavirin, a drug presenting a broad-spectrum against viral infections. SRO-91 antitumor activities were investigated on 9 strains of tumor cells and IC50 of the order of 1 μM were obtained on A431 epidermoid carcinoma cells and B16F10 skin melanoma cells. In addition, studies of ovarian tumor cell inhibitions show an interesting activity in regard to the need for new drugs for this pathology. Finally, cytotoxicity and mouse toxicity studies reveal a favorable therapeutic index for SRO-91.

Multifloroside Suppressing Proliferation and Colony Formation, Inducing S Cell Cycle Arrest, ROS Production, and Increasing MMP in Human Epidermoid Carcinoma Cell Lines A431.

Multifloroside (4), together with 10-hydroxyoleoside 11-methyl ester (1), 10-hydroxyoleoside dimethyl ester (2), and 10-hydroxyligustroside (3), are all secoiridoids, which are naturally occurring compounds that possess a wide range of biological and pharmacological activities. However, the anti-cancer activity of 1–4 has not been evaluated yet. The objective of this work was to study the anti-cancer activities of 1–4 in the human epidermoid carcinoma cell lines A431 and the human non-small cell lung cancer (NSCLC) cell lines A549. The results indicate that 1–4 differ in potency in their ability to inhibit the proliferation of human A431 and A549 cells, and multifloroside (4) display the highest inhibitory activity against A431 cells. The structure-activity relationships suggest that the o-hydroxy-p-hydroxy-phenylethyl group may contribute to the anti-cancer activity against A431 cells. Multifloroside treatment can also inhibit cell colony formation, arrest the cell cycle in the S-phase, increase the levels of reactive-oxygen-species (ROS), and mitochondrial membrane potential (MMP), but it did not significantly induce cell apoptosis at low concentrations. The findings indicated that multifloroside (4) has the tendency to show selective anti-cancer effects in A431 cells, along with suppressing the colony formation, inducing S cell cycle arrest, ROS production, and increasing MMP.

Andrographolide as a Therapeutic Agent Against Breast and Ovarian Cancers.

Andrographolide (ANDR), isolated from Andrographis paniculata, is a medicinal compound effective against infections, inflammatory disorders, and various cancers. In the present study, the effects of ANDR on NFkB (nuclear factor kappa-light-chain-enhancer of activated B cells) activation, caspase-8-mediated apoptosis and pyroptosis, and extra cellular matrix (ECM) degradation were analyzed in A431, MDA-MB231, and SKOV-3 cell lines. Results showed that ANDR inhibited the growth and proliferation of cancer cell lines by inhibiting NFkB signaling. A significant decrease in phospho-p65 level was observed upon increasing ANDR concentration in epidermoid carcinoma and breast cancer cell lines, A431 and MDA-MB231, respectively. Accordingly, upon ANDR treatment, the expression of caspase-8 was increased, whereas no significant induction of caspase-1 expression was observed. Moreover, we observed a significant increase in the expression of tissue inhibitor of metallopeptidase-1 (TIMP1) upon increasing ANDR concentration. Such induction of TIMP1 inhibited the activity of matrix metallopeptidase-7 (MMP-7), thus preventing the degradation of ECM. Therefore, as ANDR shows cytotoxicity towards cancer cells via the NFkB signal transduction pathway without inducing pyroptosis and blocks breast and ovarian cancer invasion by inhibiting MMP-7 expression through TIMP1 up-regulation, it has the potential to be developed as a drug targeting ovarian and breast cancers.