Evaluation of anticancer activity of novel platinum(II) bis(thiosemicarbazone) complex against breast cancer.

The study aims to synthesize a novel bis(thiosemicarbazone) derivative based on platinum (thioPt) and evaluate its anticancer properties against MFC-7 and MDA-MB-231 breast cancer cells. A new platinum complex was synthesised by reacting K2PtCl4 with 2,2'-(1,2-diphenylethane-1,2-diylidene)bis(hydrazine-1-carbothioamide) in ethanol in the presence of K2CO3. In the obtained complex, the platinum atom is coordinated by a conjugated system = N-NC-S-The structures of the new compound were characterised using NMR spectroscopy, HR MS, IR, and X-ray structural analysis. The obtained results of the cytotoxicity assay indicate that compound thioPt had potent anticancer activity (MCF-7: 61.03 ± 3.57 µM, MDA-MB-231: 60.05 ± 5.40 µM) with less toxicity against normal MCF-10A breast epithelial cells, even compared to the reference compound (cisplatin). In addition, subsequent experiments found that thioPt induces apoptosis through both an extrinsic (↑caspase 8 activity) and intrinsic (↓ΔΨm) pathway, which ultimately leads to an increase in active caspase 3/7 levels. The induction of autophagy and levels of proteins involved in this process (LC3A/B and Beclin-1) were examined in MCF-7 and MDA-MB-231 breast cancer cells exposed to tested compounds (thio, thioPt, cisPt) at a concentration of 50 µM for 24 h. Based on these results, it can be concluded that thio and thioPt do not significantly affect the autophagy process. This demonstrates their superiority over cisplatin, which can stimulate cancer cell survival through its effect on stimulation of autophagy.

The activity of pyrazolo[4,3-e][1,2,4]triazine and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide derivatives in monolayer and spheroid breast cancer cell cultures.

In the last decade, an increasing interest in compounds containing pyrazolo[4,3-e][1,2,4]triazine moiety is observed. Therefore, the aim of the research was to synthesise a novel sulphonyl pyrazolo[4,3-e][1,2,4]triazines (2a, 2b) and pyrazolo[4,3-e]tetrazolo[1,5-b][1,2,4]triazine sulphonamide derivatives (3a, 3b) to assess their anticancer activity. The MTT assay showed that 2a, 2b, 3a, 3b have stronger cytotoxic activity than cisplatin in both breast cancer cells (MCF-7 and MDA-MB-231) and exhibited weaker effect on normal breast cells (MCF-10A). The obtained results showed that the most active compound 3b increased apoptosis via caspase 9, caspase 8, and caspase 3/7. It is worth to note that compound 3b suppressed NF-κB expression and promoted p53, Bax, and ROS which play important role in activation of apoptosis. Moreover, our results confirmed that compound 3b triggers autophagy through increased formation of autophagosomes, expression of beclin-1 and mTOR inhibition. Thus, our study defines a possible mechanism underlying 3b-induced anti-cancer activity against breast cancer cell lines.

Evaluation of Oromucosal Natural Gum-Based Emulgels as Novel Strategy for Photodynamic Therapy of Oral Premalignant Lesions.

Photodynamic therapy (PDT) recently has been shown as a promising option in the treatment of premalignant lesions of the soft oral tissues. Effective delivery of photosensitizer is challenging due to poor drug adherence to the oromucosal epithelium. In the present work, emulgels composed of natural polysaccharide gums (tragacanth, xanthan and gellan) were evaluated as novel oromucosal platforms of delta-aminolevulinic acid (ALA) for PDT. Apart from mucoadhesive and textural analysis, the specific steps involved studies on drug penetration behavior and safety profile using a three-dimensional human oral epithelium model (HOE). All designed emulgels presented greater mucoadhesiveness when compared to commercial oromucosal gel. Incorporation of ALA affected textural properties of emulgels, and tragacanth/xanthan formulation with greater hardness and cohesiveness exhibited a protective function against the mechanical tongue stress. Permeability studies revealed that ALA is capable of penetrating across oromucosal epithelium by passive transport and all formulations promoted its absorption rate when compared to a commercial topical product with ALA. Importantly, the combination of tragacanth and xanthan profoundly enhanced photosensitizer retention in the buccal epithelium. Tested samples performed negligible reduction in cell viability and moderately low IL-1ß release, confirming their non-irritancy and compatibility with HOE. Overall, the presented findings indicate that tragacanth/xanthan emulgel holds promise as an oromucosal ALA-carrier for PDT strategy.

Multi-Targeting Anticancer Activity of a New 4-Thiazolidinone Derivative with Anti-HER2 Antibodies in Human AGS Gastric Cancer Cells.

Combining chemotherapy with immunotherapy still remains a regimen in anticancer therapy. Novel 4-thiazolidinone-bearing hybrid molecules possess well-documented anticancer activity, and together with anti-HER2 antibodies, may represent a promising strategy in treating patients with gastric cancer with confirmed human epidermal growth factor receptor 2 (HER2) expression. The aim of the study was to synthesize a new 4-thiazolidinone derivative (Les-4367) and investigate its molecular mechanism of action in combination with trastuzumab or pertuzumab in human AGS gastric cancer cells. AGS cell viability and antiproliferative potential were examined. The effect of the tested combinations as well as monotherapy on apoptosis and autophagy was also determined. Metalloproteinase-2 (MMP-2), intercellular adhesion molecule 1 (ICAM-1), pro-inflammatory and anti-inflammatory cytokine concentrations were also demonstrated by the ELISA technique. We proved that pertuzumab and trastuzumab were very effective in increasing the sensitivity of AGS gastric cancer cells to novel Les-4367. The molecular mechanism of action of the tested combination is connected with the induction of apoptosis. Additionally, the anticancer activity is not associated with the autophagy process. Decreased concentrations of pro-inflammatory cytokines, MMP-2 and ICAM-1-were observed. The novel combination of drugs based on anti-HER2 antibodies with Les-4367 is a promising strategy against AGS gastric cancer cells.

Molecular design, synthesis and anticancer activity of new thiopyrano[2,3-d]thiazoles based on 5-hydroxy-1,4-naphthoquinone (juglone).

A series of 11-substituted 9-hydroxy-3,5,10,11-tetrahydro-2H-benzo[6,7]thiochromeno[2,3-d][1,3]thiazole-2,5,10-triones 3.1-3.13 were synthesized via hetero-Diels-Alder reaction of 5-ene-4-thioxo-2-thiazolidinones and 5-hydroxy-1,4-naphthoquinone (juglone). The structure of newly synthesized compounds was established by means of spectral data and a single-crystal X-ray diffraction analysis. The synthesized compounds were tested on a panel of cell lines representing different types of cancer as well as normal and pseudonormal cells and peripheral human blood lymphocytes. Compound 3.10 was found to be the most active derivative, exhibiting a cytotoxic effect similar to doxorubicin's one (IC50 ranged from 0.6 to 5.98 µM), but less toxic to normal and pseudonormal cells. All synthesized compounds were able to interact with DNA, although their anticancer activity did not correlate with the potency of interaction with DNA. The status of p53 in colorectal cancer cells correlated with the activity of the synthesized derivatives 3.1, 3.7, and 3.10. Compound 3.10 did not have an acute toxic effect on the body of С57BL/6 mice, unlike the well-known anticancer drug doxorubicin, which was used as a positive control. The injection of 3.10 (20 mg/kg) to mice had no effect on the counts of leukocytes, erythrocytes, platelets and hemoglobin level in their blood, in contrast to doxorubicin, which caused anemia and leukopenia, indicating bio-tolerance of 3.10in vivo.

Tamoxifen Modulates the Immune Landscape of the Tumour Microenvironment: The Paired Siglec-5/14 Checkpoint in Anti-Tumour Immunity in an In Vitro Model of Breast Cancer.

Since the role of sialome-Siglec axis has been described as a regulatory checkpoint of immune homeostasis, the promotion of stimulatory or inhibitory Siglec-related mechanisms is crucial in cancer progression and therapy. Here, we investigated the effect of tamoxifen on the sialic acid-Siglec interplay and its significance in immune conversion in breast cancer. To mimic the tumour microenvironment, we used oestrogen-dependent or oestrogen-independent breast cancer cells/THP-1 monocytes transwell co-cultures exposed to tamoxifen and/or ß-estradiol. We found changes in the cytokine profiles accompanied by immune phenotype switching, as measured by the expression of arginase-1. The immunomodulatory effects of tamoxifen in THP-1 cells occurred with the altered SIGLEC5 and SIGLEC14 genes and the expression of their products, as confirmed by RT-PCR and flow cytometry. Additionally, exposure to tamoxifen increased the binding of Siglec-5 and Siglec-14 fusion proteins to breast cancer cells; however, these effects appeared to be unassociated with oestrogen dependency. Our results suggest that tamoxifen-induced alterations in the immune activity of breast cancer reflect a crosstalk between the Siglec-expressing cells and the tumour's sialome. Given the distribution of Siglec-5/14, the expression profile of inhibitory and activatory Siglecs in breast cancer patients may be useful in the verification of therapeutic strategies and predicting the tumour's behaviour and the patient's overall survival.

Thiosemicarbazide Derivatives Targeting Human TopoIIα and IDO-1 as Small-Molecule Drug Candidates for Breast Cancer Treatment.

In 2020, breast cancer became the most frequently diagnosed type of cancer, with nearly 2.3 million new cases diagnosed. However, with early diagnosis and proper treatment, breast cancer has a good prognosis. Here, we investigated the effect of thiosemicarbazide derivatives, previously identified as dual inhibitors targeting topoisomerase IIα and indoleamine-2,3-dioxygenase 1 (IDO 1), on two distinct types of breast cancer cells (MCF-7 and MDA-MB-231). The investigated compounds (1-3) selectively suppressed the growth of breast cancer cells and promoted apoptosis via caspase-8- and caspase-9-related pathways. Moreover, these compounds caused S-phase cell cycle arrest and dose-dependently inhibited the activity of ATP-binding cassette transporters (MDR1, MRP1/2 and BCRP) in MCF-7 and MDA-MB-231 cells. Additionally, following incubation with compound 1, an increased number of autophagic cells within both types of the investigated breast cancer cells was observed. During preliminary testing of ADME-Tox properties, the possible hemolytic activities of compounds 1-3 and their effects on specific cytochrome P450 enzymes were evaluated.

ONCOBREAST-TEST Is a Quick Diagnostic, Prognostic and Predictive Method of Response to Systemic Treatment.

ONCOBREAST-TEST is a diagnostic and therapeutic procedure that is part of the comprehensive care of a patient with breast cancer.: Chemosensitivity of cancer cells was assessed using the MTT test, morphological assessment of cells, LDH activity in the culture medium, and flow cytometry technique (apoptosis, proliferation, CD24, CD44, GATA3, cytokeratin, Ki-67). Diagnostic tools included panels of simple tests which could be used to accurately predict the chemosensitivity of tumor cells previously isolated from a patient, even before actual chemotherapy. The proposed procedure allows for a simple (based on MTT results, cell morphology, LDH concentration), minimally invasive, quick, and accurate assessment of the sensitivity of breast cancer cells to the drugs used and, to select the most effective treatment plan as part of personalized therapy. In a patient with NOS G3, the most promising therapy will be docetaxel with cyclophosphamide and in the case of a patient with NOS G1, paclitaxel alone and in combination with trastuzumab. The implementation of such a procedure would undoubtedly increase the effectiveness of chemotherapy, reduce side effects by excluding drugs that are ineffective before using them, protect the patient's health, and shorten the treatment time, bringing economic and social benefits.

Assessment of an Anticancer Effect of the Simultaneous Administration of MM-129 and Indoximod in the Colorectal Cancer Model.

(1) Background: The purpose of the given study was to examine the antitumor activity of the simultaneous administration of MM-129, a 1,2,4-triazine derivative, and indoximod (IND), the kynurenine pathway inhibitor, toward colon cancer. (2) Methods: The efficiency of the co-administration of the studied compounds was assessed in xenografted zebrafish embryos. Then, the effects of the combined administration of compounds on cellular processes such as cell viability, apoptosis, and intracellular signaling pathways were evaluated. In vitro studies were performed using two colorectal cancer cell lines, namely, DLD-1 and HT-29. (3) Results: The results indicated that the simultaneous application of MM-129 and indoximod induced a stronger inhibition of tumor growth in zebrafish xenografts. The combination of these compounds intensified the process of apoptosis by lowering the mitochondrial potential, enhancing the externalization of phosphatidylserine (PS) and activation of caspases. Additionally, the expression of protein kinase B (AKT) and indoleamine 2,3-dioxygenase-(1IDO1) was disrupted under the applied compound combination. (4) Conclusions: Simultaneous targeting of ongoing cell signaling that promotes tumor progression, along with inhibition of the kynurenine pathway enzyme IDO1, results in the enhancement of the antitumor effect of the tested compounds against the colon cancer cells.

Biosynthesized Gold, Silver, Palladium, Platinum, Copper, and Other Transition Metal Nanoparticles.

Nanomedicine is a potential provider of novel therapeutic and diagnostic routes of treatment. Considering the development of multidrug resistance in pathogenic bacteria and the commonness of cancer, novel approaches are being sought for the safe and efficient synthesis of new nanoparticles, which have multifaceted applications in medicine. Unfortunately, the chemical synthesis of nanoparticles raises justified environmental concerns. A significant problem in their widespread use is also the toxicity of compounds that maintain nanoparticle stability, which significantly limits their clinical use. An opportunity for their more extensive application is the utilization of plants, fungi, and bacteria for nanoparticle biosynthesis. Extracts from natural sources can reduce metal ions in nanoparticles and stabilize them with non-toxic extract components.

LC-PDA-MS and GC-MS Analysis of Scorzonera hispanica Seeds and Their Effects on Human Breast Cancer Cell Lines.

Scorzonera hispanica is an herbaceous perennial cultivated in Central and Southern Europe. This study aimed to qualitatively and quantitatively evaluate the composition of oil, extracts, and fractions (SH1-SH12) obtained from S. hispanica seeds. Furthermore, an evaluation of biological activities in breast cancer cell lines was also performed. GC-MS analysis revealed that the primary components of the seed oil (SH12) were fatty acids and ß-sitosterol. In the evaluation of extracts (SH1-SH3, SH8-SH10) and fractions (SH4-SH7, SH11) composition, the presence of apigenin, derivatives of p-coumaric and caffeic acids, was reported. In the biological assays, methanolic extract (SH1), diethyl ether (SH4), and chloroform (SH11) fractions exhibited cytotoxicity toward cells. The highest activity was observed for fatty acids- and 3,4-dimethoxycinnamate-rich SH11 (IC50: 399.18 µg/mL for MCF-7, 781.26 µg/mL for MDA-MB-231). SH11 was also observed to induce apoptosis in MCF-7 cells (52.4%). SH1, SH4, and SH11 attenuate signaling pathways and affect the expression of apoptosis-, autophagy-, and inflammation-related proteins. SH12 was non-toxic toward either cancer or normal cell lines in concentrations up to 1 mg/mL. The results suggest that S. hispanica seeds exhibit a wide range of potential uses as a source of oil and bioactive compounds for complementary therapy of breast cancer.

Development of Novel Pyridine-Thiazole Hybrid Molecules as Potential Anticancer Agents.

Novel pyridine-thiazole hybrid molecules were synthesized and subjected to physico-chemical characterization and screening of their cytotoxic action towards a panel of cell lines derived from different types of tumors (carcinomas of colon, breast, and lung, glioblastoma and leukemia), and normal human keratinocytes, for comparison. High antiproliferative activity of the 3-(2-fluorophenyl)-1-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-propenone 3 and 4-(2-{1-(2-fluorophenyl)-3-[4-methyl-2-(pyridin-2-ylamino)-thiazol-5-yl]-3-oxopropylsulfanyl}-acetylamino)-benzoic acid ethyl ester 4 was revealed. The IC50 of the compound 3 in HL-60 cells of the acute human promyelocytic leukemia was 0.57 µM, while in the pseudo-normal human cell lines, the IC50 of this compound was >50 µM, which suggests that the compounds 3 and 4 might be perspective anticancer agents. The detected selectivity of the derivatives 3 and 4 for cancer cell lines inspired us to study the mechanisms of their cytotoxic action. It was shown that preincubation of tumor cells with Fluzaparib (inhibitor of PARP1) reduced the cytotoxic activity of the derivatives 3 and 4 by more than twice. The ability of these compounds to affect DNA nativity and cause changes in nucleus morphology allows for the suggestion that the mechanism of action of the novel pyridine-thiazole derivatives might be related to inducing the genetic instability in tumor cells.

Synthesis and Anticancer Activity of 1,3,4-Thiadiazoles with 3-Methoxyphenyl Substituent.

Based on the results of previous work, we designed and synthesized 1,3,4-thiadiazole derivatives. The cytotoxic activity of the obtained compounds was then determined in biological studies using MCF-7 and MDA-MB-231 breast cancer cells and a normal cell line (fibroblasts). The results showed that all compounds displayed weak anticancer activity towards two breast cancer lines: an estrogen-dependent cell line (MCF-7) and an estrogen-independent cell line (MDA-MB-231). The compound most active towards MCF-7 breast cancer cells was SCT-4, which decreased DNA biosynthesis to 70% ± 3 at 100 µM. The mechanism of the anticancer action of 1,3,4-thiadiazole was also investigated. We choose a set of the most investigated proteins, which are attractive anticancer targets. In silico studies demonstrated a possible multitarget mode of action for the synthesized compounds but the most likely mechanism of action for the new compounds is connected with the activity of caspase 8.

Novel Selenoesters as a Potential Tool in Triple-Negative Breast Cancer Treatment.

Disturbing cancer statistics, especially for breast cancer, are becoming a rationale for the development of new anticancer therapies. For the past several years, studies have been proving a greater role of selenium in the chemoprevention of many cancers than previously considered; hence, a trend to develop compounds containing this element as potential agents with anticancer activity has been set for some time. Therefore, our study aimed to evaluate the anticancer activity of novel selenoesters (EDA-71, E-NS-4) in MCF-7 and MDA-MB-231 human breast cancer cells. The assays evaluating proliferation and cell viability, and flow cytometer analysis of apoptosis/autophagy induction, changes in mitochondrial membrane potential, disruption of cell cycle phases, and protein activity of mTOR, NF-κB, cyclin E1/A2, and caspases 3/7, 8, 9, 10 were performed. The obtained results indicate that the tested selenoesters are highly cytotoxic and exhibit antiproliferative activity at low micromolar doses (<5 µM) compared with cisplatin. The most active compound­EDA-71­highly induces apoptosis, which proceeds via both pathways, as evidenced by the activation of all tested caspases. Furthermore, we observed the occurrence of autophagy (↓ mTOR levels) and cell cycle arrest in the S or G2/M phase (↓ cyclin E1, ↑ cyclin A2).

An Overview of the Importance of Transition-Metal Nanoparticles in Cancer Research.

Several authorities have implied that nanotechnology has a significant future in the development of advanced cancer therapies. Nanotechnology makes it possible to simultaneously administer drug combinations and engage the immune system to fight cancer. Nanoparticles can locate metastases in different organs and deliver medications to them. Using them allows for the effective reduction of tumors with minimal toxicity to healthy tissue. Transition-metal nanoparticles, through Fenton-type or Haber-Weiss-type reactions, generate reactive oxygen species. Through oxidative stress, the particles induce cell death via different pathways. The main limitation of the particles is their toxicity. Certain factors can control toxicity, such as route of administration, size, aggregation state, surface functionalization, or oxidation state. In this review, we attempt to discuss the effects and toxicity of transition-metal nanoparticles.

Wound Healing Properties of Jasione montana Extracts and Their Main Secondary Metabolites.

The effects of different extracts obtained from Jasione montana L. (JM1-JM6) and their main metabolites on biological processes during wound healing were evaluated. The effect on wound closure in the scratch test was established, and collagen type I synthesis and anti-inflammatory effects were assessed by flow cytometry in a human dermal fibroblast model (PCS-201-012). Additionally, the antioxidant activity (DPPH and FRAP) and degree of inhibition of elastase participating in the proliferation processes of skin fibroblasts were determined in an in vitro model. The extracts and fractions were analyzed using high-performance liquid chromatography-photodiode array detection (HPLC-PDA) to quantitatively characterize their main polyphenolic compounds. The high antioxidant activity of the JM4-JM5 fractions correlated with the content of luteolin and its derivative 7-O-glucoside. Luteolin also showed the highest anti-elastase activity with an IC50 value of 39.93 ± 1.06 µg/mL, and its substantial content in the JM4 fraction presumably determines its activity (359.03 ± 1.65 µg/mL). At lower concentrations (<50 µg/mL) of all extracts, cell proliferation and migration were significantly stimulated after 24 h of treatment. The stimulation of cell migration was comparable with that of allantoin, which was used as a positive control. However, most of the tested extracts showed limited capacity to affect collagen type I biosynthesis. Moreover, the tested samples exhibited a complex effect on cytokine secretion, and the strongest anti-inflammatory activity through the moderation of IL-1ß, IL-6 and IL-8 was observed for JM4 and luteolin. Based on the obtained results of the quantitative analysis, the anti-inflammatory activity of JM4 may be due to the high content of luteolin. In summary, extracts from J. montana, which is flavonoid-rich, promote the viability and accelerate the migration of fibroblasts as well as moderate oxidant and inflammatory processes and elastase activity. Hence, they may be potentially useful for topical therapeutic applications to stimulate the wound healing process.

Chitosan-Enriched Solution Blow Spun Poly(Ethylene Oxide) Nanofibers with Poly(Dimethylsiloxane) Hydrophobic Outer Layer for Skin Healing and Regeneration.

Chitosan (CS)/poly(ethylene oxide) (PEO)-based nanofiber mats have attracted particular attention as advanced materials for medical and pharmaceutical applications. In the scope of present studies, solution blow spinning was applied to produce nanofibers from PEO and CS and physicochemical and biopharmaceutical studies were carried out to investigate their potential as wound nanomaterial for skin healing and regeneration. Additional coating with hydrophobic poly(dimethylsiloxane) was applied to favor removal of nanofibers from the wound surface. Unmodified nanofibers displayed highly porous structure with the presence of uniform, randomly aligned nanofibers, in contrast to coated materials in which almost all the free spaces were filled in with poly(dimethylsiloxane). Infrared spectroscopy indicated that solution blow technique did not influence the molecular nature of native polymers. Obtained nanofibers exhibited sufficient wound exudate absorbency, which appears beneficial to moisturize the wound bed during the healing process. Formulations displayed greater tensile strength as compared to commercial hydrofiber-like dressing materials comprised of carboxymethylcellulose sodium or calcium alginate, which points toward their protective function against mechanical stress. Coating with hydrophobic poly(dimethylsiloxane) (applied to favor nanofiber removal from the wound surface) impacted porosity and decreased both mechanical properties and adherence to excised human skin, though the obtained values were comparable to those attained for commercial hydrofiber-like materials. In vitro cytotoxicity and irritancy studies showed biocompatibility and no skin irritant response of nanofibers in contact with a reconstituted three-dimensional human skin model, while scratch assay using human fibroblast cell line HDFa revealed the valuable potential of CS/PEO nanofibers to promote cell migration at an early stage of injury.

2-{5-[(Z,2Z)-2-Chloro-3-(4-nitrophenyl)-2-propenylidene]-4-oxo-2-thioxothiazolidin-3-yl}-3-methylbutanoic Acid as a Potential Anti-Breast Cancer Molecule.

It was established that the synthesis of hybrid molecules containing a thiazolidinone and a (2Z)-2-chloro-3-(4-nitrophenyl)prop-2-ene structural fragments is an effective approach for the design of potential anticancer agents. Given the results of the previous SAR-analysis, the aim of the study was to synthesize a novel 4-thiazolidinone derivative Les-3331 and investigate its molecular mechanism of action in MCF-7 and MDA-MB-231 breast cancer cells. The cytotoxic properties and antiproliferative potential of Les-3331 were determined. The effect of the tested compound on apoptosis induction and mitochondrial membrane potential was checked by flow cytometry. ELISA was used to determine caspase-8 and caspase-9, LC3A, LC3B, Beclin-1, and topoisomerase II concentration. Additionally, PAMPA, in silico or in vitro prediction of metabolism, CYP3A4/2D6 inhibition, and an Ames test were performed. Les-3331 possesses high cytotoxic and antiproliferative activity in MCF-7 and MDA-MB-231 breast cancer cells. Its molecular mechanism of action is associated with apoptosis induction, decreased mitochondrial membrane potential, and increased caspase-9 and caspase-8 concentrations. Les-3331 decreased LC3A, LC3B, and Beclin-1 concentration in tested cell lines. Topoisomerase II concentration was also lowered. The most probable metabolic pathways and no DDIs risk of Les-3331 were confirmed in in vitro assays. Our studies confirmed that a novel 4-thiazolidinone derivative represents promising anti-breast cancer activity.

Anti-cancer effects of pyrazole-platinum(II) complexes combined with anti-MUC1 monoclonal antibody versus monotherapy in DLD-1 and HT-29 colon cancer cells.

The membrane-bound MUC1 mucin is overexpressed and aberrantly glycosylated in many epithelium origin cancers. One of the promising strategies in cancer therapy is combining monoclonal antibodies against cancer related antigens, like MUC1, with chemotherapeutics. In the study we evaluated the potency of cisplatin (cisPt), two pyrazole-platinum(II) complexes PtPz4, PtPz6, and anti-MUC1 mAb applied as monotherapy, as well as the chemotherapeutics administrated with antibody, towards apoptotic response and cancer-related carbohydrate antigens (TACAs) in DLD-1 and HT-29 colon cancer cells. To assess the impact of the tested compounds on the examined factors flow cytometry, RT-PCR, Western blotting and ELISA were utilized. The combined therapy was more potent than monotherapy towards Bcl-2, Bid, caspases and TACAs of both cell lines. Combined therapy applied in DLD-1 cells induced apoptosis, was more effective than monotherapy in relation to p53, Bcl-xL, Bax, and Bim. In HT-29 cells, anti-MUC1 administrated with the drugs was more potent than monotherapy towards Bad. The proposed anti-MUC1/cisPt and pyrazole-platinum(II) complexes PtPz4, PtPz6 combined therapy may be promising anti-colon cancer therapy.

Anti-Cancer Potential of Afzelin towards AGS Gastric Cancer Cells.

Afzelin demonstrates anti-inflammatory and anti-cancer properties. Our purpose was to assess its influence on apoptosis, Bax, caspases, MUC1, cancer-related carbohydrate antigens, enzymes participating in their formation, and galectin-3 in AGS gastric cancer cells. A total of 60 and 120 µM afzelin was used in all experiments. Flow cytometry was applied to determine apoptotic response. Western blotting and RT PCR were used to detect the expression of mentioned factors. Flavonoid at higher concentration revealed slight apoptotic respond. Bax, caspase-3, -8, -9 increased upon afzelin action. Stimulatory effect of the flavonoid on MUC1 cytoplasmic tail and extracellular domain in cell lysates and on MUC1 gene was revealed. MUC1 release into the culture medium was inhibited by the flavonoid. The 60 µM afzelin dose stimulated GalNAcTL5 protein expression and inhibited C1GalT1. ST6GalNAcT mRNA was inhibited by both flavonoid doses. ST3GalT was inhibited by 120 µM afzelin on protein and mRNA level. Lewisa/b protein was reduced by both afzelin concentrations. FUT3 and FUT4 mRNA was inhibited by 120 µM dose of afzelin. Galectin-3 protein increased in cell lysates and decreased in culture supernatant by 60 and 120 µM flavonoid. Galectin-3 gene expression was stimulated by two used concentrations of afzelin in comparison to control. We conclude that afzelin can be considered as the potential anti-cancer agent, supporting conventional cancer treatment.