Changes of c-myc expression in b16 melanoma cells induced by 8-chloroadenosine-3′, 5′-monophosphate and tiazofurin

The aim of this study was to investigate the in vitro effects of 8- chloroadenosine 3′, 5′-monophosphate (8-Cl-cAMP) and tiazofurin (TR) on the expression of c-myc gene in B16/F10 and B16/C3 mouse melanoma cells. Exponentially growing cells were treated with 8-Cl-cAMP or TR (5µmol - 25µmol) for 6h and 24h. The level of c-myc expression, estimated by RT-PCR, did not significantly change in B16/F10 cells after treatment with 8-Cl-cAMP or TR. Similar results were obtained in B16/C3 cells after treatment with 8-Cl-cAMP. The level of c-myc expression has shown a significant increase in B16/C3 cells after treatment with TR. Further studies of these agents will lead to better understanding of molecular mechanisms of their action.Physical chemistry 2004 : 7th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 21-23 September 200

Effects of short time exposure of HTB140 melanoma cells to fotemustine and dacarbazine

Different experimental set-ups were designed to study cytotoxic and cytoststic effects on HTB140 melanoma cells after 1 h treatment with fotemustine (FM) or dacarbazine (DTIC). FM induced dose dependent cell inactivation, boosted by its toxicity, particularly for higher doses. DTIC treatment for 1 h was insufficient to provoke almost any effect on melanoma cells. Good correlation between viability and proliferation assays applied was detected for both drugs.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Sensitivity of HTB140 cell exposed to protons and alkylating agents

Malignant melanoma is a highly aggressive cancer with a poor prognosis due to resistance to radiotherapy and chemotherapy regimens. The mainstay of treatment remains DNA-alkylatingagent dacarbazine (DTIC). Fotemustine (FM), chloroethylnitrosourea agent, also has demonstrated significant antitumoral effects in malignantmelanoma. However, the resistance of melanoma cells limits their clinical application. In order to enhance the inhibition of melanoma cell growth, in this study, combined treatment of FM and DTIC with proton irradiation, was investigated. We analyzed the effects of combined treatment on HTB140 melanoma cell viability and proliferation. Significant inhibition of cell growth, especially cell proliferation, was obtained after treatment with protons and FM compare to single irradiation or drug treatment. Treatment with protons and DTIC has shown improved growth inhibition compare to appropriate single drug treatment, but not compare to irradiation as a single treatment.Physical chemistry 2006 : 8th international conference on fundamental and applied aspects of physical chemistry; Belgrade (Serbia); 26-29 September 200

Cancer cell death induced by ruthenium complexes

Summary. Cancer is a complex and often fatal disease characterized by uncontrolled cell division. The most commonly used chemotherapeutics target rapidly dividing cancer cells but, at the same time, damage healthy dividing cells. New metal-based complexes, such as ruthenium complexes, that possess cytotoxic properties, have been developed to overcome these challenges. Ruthenium complexes achieve their antitumor effect mainly by inducing apoptosis. In recent years, induction of other types of cell death, such as ferroptosis and autophagy, was also reported. The dual role of autophagy in cancer cells is a major challenge for the application of metallocomplexes in cancer treatment, either as inducers or inhibitors of autophagy. Also, the effect of ruthenium complexes on other cellular processes such as cell cycle, cell migration, and adhesion are promising approaches in cancer treatment. Our results indicated a significant influence of Ru(II) complexes on these processes in melanoma, cervical and pancreatic cancer. The aim of this review is to summarize the latest data on the effect of ruthenium complexes on different types of cell death

The influence of Fe(III) incorporation on anti-cancer potential of a Wells-Dawson nanocluster

The objective of this study was to evaluate in vitro the antitumor properties of Fe(III)- substituted monolacunary Wells-Dawson polyoxotungstate, K7[FeIII(α2-P2W17O61)(H2O)] (FeWD) using cervical carcinoma HeLa cells as a model system. HeLa cells were exposed in vitro to FeWD within the concentration range from 0.001 to 1 mM, for 24, 48, and 72 hours. The studied Fe(III)- substituted polyoxotungstate affected HeLa cell viability in a concentration- and time-dependent manner. The obtained IC50 values (µM), as an indicator of the cytotoxic potential of FeWD, were: 16.64 ± 0.49, 10.75 ± 0.97, and 9.64 ± 0.19 for 24-, 48-, and 72-hour treatment, respectively. FeWD exhibited a stronger antitumor potential against HeLa cells than the structurally similar monolacunary Wells-Dawson polyoxotungstate, K10P2W17O61.20H2O (lacunary WD). Lacunary WD achieved IC50 at 24,11 µM after 24-hour exposure, which is about 44% higher concentration compared to the corresponding IC50 obtained for FeWD. This indicates that incorporating Fe(III) might be a new strategy for improving the antitumor efficacy of polyoxometalates as promising candidates for next-generation chemotherapeutics.ICCBIKG 2023 : 2nd International Conference on Chemo and Bioinformatics, 28-29 September 2023, Kragujevac, Serbi

In vitro cytotoxic activity of a monolacunary Wells-Dawson nanocluster against cervical carcinoma HeLa cells

The aim of this study was to assess in vitro cytotoxic activity of a monolacunary Wells- Dawson nanocluster, α2-K10P2W17O61.20H2O (lacunary WD) against cervical carcinoma HeLa cells as a commonly used model system for the evaluation of antitumor properties. After HeLa cells had been exposed to the investigated polyoxotungstate (the concentration range of 0.001 - 1 mM) for 24, 48, and 72 h, relative cell viability (expressed as a percentage of control) was determined. The obtained results showed that lacunary WD affected HeLa cell viability in a concentration- and time-dependent manner. IC50 values (in μM), calculated using sigmoidal fitting experimental plots, were as follows: 24.11 ± 9.95, 12.74 ± 0.096, and 11.48 ± 0.12 for 24, 48, and 72 hours treatment, respectively. In comparison with cisplatin, (positive control), IC50 values (μM) for 24 hours treatment were similar – 24.11 (lacunary WD) vs. 24.49 (cisplatin). However, after 48 and 72 hours IC50 obtained for cisplatin were found to be lower – 8.81 and 4.93 μM, respectively. Accordingly, the studied WD polyoxotungstate could not be regarded as a superior anticancer agent in comparison with the standard chemotherapeutic. Nevertheless, this studied nanocluster deserves attention as a promising antitumor therapeutic and as a good platform for the design of next-generation metal-based anticancer agents.ICCBIKG 2023 : 2nd International Conference on Chemo and Bioinformatics, 28-29 September 2023, Kragujevac, Serbi

Prooxidative and antimigratory effects of cerium oxide nanoparticles on melanoma and pancreatic cancer cells

The development of new types of nanoparticles has become the focus of biomedical research in recent years. Cerium oxide nanoparticles (CONP) have shown particularly promising results as antitumor agents with a selective effect on tumor and normal cells. On the other side, melanoma and pancreatic carcinoma are among the most aggressive types of cancer with no satisfactory therapy1,2 . Considering that, they represent important model systems for studying new treatment approaches. In this study, the antitumor potential of CONP (size below 10 nm) was studied on human A375 melanoma and PANC-1 pancreatic carcinoma cells. The obtained results indicated that analyzed CONP significantly inhibited clonogenic survival, with the number of colonies reduced on ~30% in A375 cells, while treated PANC-1 cells didn’t form colonies. Growth inhibition was followed by G 2 cell cycle arrest (9% for A375, 17% for PANC-1). Percent of apoptotic PANC-1 cells was 38%, whereas ROS production increased for 78%. CONP significantly reduced metastatic potential through the decrease in cell migration and the increase in cell adhesiveness (up to 30 and 40% for A375 and PANC-1 respectively). These findings emphasize the significant CONP antitumor potential, based on the increase in ROS production, as well as a reduction of A375 and PANC-1 metastatic potential

Examination of Prooxidative Activity of Red Wine in Melanoma Cells

Melanoma is responsible for 75% of all deaths from skin cancer. Its lethality arises from its rapid progression, easy metastasis and drug-resistance as well. Red wine is a natural product rich in polyphenolic compounds with potent anticancer activities. It seems that in cancer cells these compounds behave as prooxidants initiating reactive oxygen species mediated cellular DNA breakage and consequent cell death. The aim of this study was to investigate prooxidative activity of red wine samples (Merlot variety, commercial as well as VCR1 and VCR101 clonal wines) in melanoma A375 cells, through measuring the relationship of reduced and oxidized form of glutathione (GSH/GSSG) and comparison with the GSH/GSSG ratio in control (untreated melanoma cells). The data obtained showed that tested red wine samples decrease GSH/GSSG ratio in A375 cells compared to control (4.6 ± 0), with the largest decrease noticed in treatment with VCR101 wine (0.66 ± 0.05)

Bismuth ferrite nanoparticles increase ROS production and p62 expression in A375 melanoma and HeLa cells

Background: Cancer nanomedicine is a rapidly developing fi eld that uses nanoparƟ cles (NPs) for the diagnosis and treatment of cancer. Currently, many nanomaterials with diff erent shapes, sizes, structures, and composiƟ ons have been invesƟ gated to produce eff ecƟ ve anƟ cancer NPs. The interest in the biomedical applicaƟ ons of bismuth-containing nanoparƟ cles, such as bismuth ferrite (BFO-NP) is a result of their promising properƟ es such as cost-effecƟ veness, chemical inertness, high stability, and simplicity of funcƟ onalizaƟ on. Material and Methods: A375 human melanoma and HeLa cervical carcinoma cells were used to study the anƟ tumor acƟ vity of BFO-NP. Clonogenicity of treated cells was analyzed by colony forming assay, while cell death was examined using fl ow cytometry. DCF-DA fl uorescent assay was applied to measure ROS producƟ on. Protein expression of p62 and TfR1 was detected by Western blot. Cell migraƟ on was analyzed using a wound scratch assay, while an SRB assay was used to assess cell adhesion. Results: BFO-NP (200 ng/L) signifi cantly reduced the clonogenicity of A375 and HeLa cells by 46 and 60%, respecƟ vely. Detected ROS producƟ on was increased considerably, especially for A375 melanoma cells, and amounted to 400%. The number of late apoptoƟ c and/or necroƟ c cells increased by 10-12%, compared to the control. Signifi cantly increased expression of autophagy-related protein p62 was observed in both cell lines aŌ er BFO-NP treatment. Ferroptosis-related transferrin receptor (TfR1) expression was slightly increased in treated A375 end HeLa cells (~14%). The noƟ ced increase in cell adhesion ranged from 20-30% followed by a decrease in cell migraƟ on. Conclusion:BFO-NP is a promising anƟ tumor agent with a signifi cant inhibitory eff ect on A375 and HeLa cell growth and metastaƟ c potenƟ al. Molecular mechanisms involved in these processes include ROS producƟ on and increased p62 expression. Reduced metastaƟ c potenƟ al resulted from the inducƟ onof cell adhesion and decreased cell migraƟ on.The first number of Oncology Insights includes Proceedings book of The Sixth Congress of the Serbian Association for Cancer Research with international participation (Oct 2-4, 2023, Belgrade

Antitumor effect of Ru(II) complex on A375 and HeLa cell growth, migration and adhesion ability

Platinum-based complexes represent the mainstay of treatment for various cancer types. However, their usage is often restricted by numerous side effects or intrinsic and acquired resistance. Therefore, significant research efforts have focused on developing therapeutics based on other transition metals, such as ruthenium 1,2. In this study, effects of transition metal complex, cis-dichlorobis (2,2ʹ-bipyridyl-4,4ʹ-dicarboxylic acid)ruthenium(II) (Ru(II) complex) were analyzed on A375 human melanoma and HeLa cell growth, adhesion ability andmigration. Cell viability assay indicated significant antitumor activity of Ru(II) complex on A375 (~60% of control) up to 72 h after treatment, but not on HeLa cells. However, analysis by clonogenic assay showed that growth of both cell lines was decreased 7 days after treatment. Growth inhibition was followed by G1 phase cell cycle arrest (5–10% G1 increase for A375 and 5–8% for HeLa cells compared to control). Moreover, Ru(II) complex increased adhesivity of A375 and HeLa cells by 11 and 16 % respectively and decreased cell migration, as shown by scratch assay. The obtained results indicate that the analyzed Ru(II) complex is a promising metallodrug, as itinduced growth inhibition of A375 and HeLa cells through induction of G1 arrest and decreased metastatic potential of these cells through the increase ofadhesivity and decrease of cell migration