scholarly journals The Effect of Plasma Activated Medium and PBS on Human Melanoma Cells Compared With Other Cancer and Normal Cells

2021 ◽  
Author(s):  
Dominika Sersenová ◽  
Zdenko Machala ◽  
Vanda Repiská ◽  
Helena Gbelcová
Keyword(s):  
Cancer Cells ◽  
Treatment Time ◽  
Ambient Air ◽  
Melanoma Cells ◽  
Clinical Applications ◽  
Dermal Fibroblasts ◽  
Apoptosis Induction ◽  
Normal Cells ◽  
Anticancer Effects ◽  
Cold Plasmas

Plasma medicine is a new field focusing on biomedical and clinical applications of cold physical plasmas, including their anticancer effects. Cold plasmas can be applied directly or indirectly as plasma activated liquids (PAL). The effect of plasma activated cell growth medium (PAM) and plasma activated phosphate buffered saline (PAPBS) were tested using a plasma pen generating streamer corona discharge in ambient air, on different cancer cell lines (melanoma A375, glioblastoma LN229 and pancreatic cancer MiaPaCa-2) and normal cells (human dermal fibroblasts HDFa). The viability reduction and apoptosis induction were detected in all cancer cells after incubation in PAL. In melanoma cells we focused on detailed insights to the apoptotic pathways. The anticancer effects depend on the plasma treatment time or PAL concentration. The first 30 minutes of incubation in PAL were enough to start processes leading to the cell death. In fibroblasts, no apoptosis induction was observed, only PAPBS, activated for longer time, slightly decreased their viability. Anticancer effects of PAM and PAPBS on cancer cells showed selectivity compared to normal fibroblasts, depended on correctly chosen activation time and PAL concentration. This selectivity, supported by optimum ratio of hydrogen peroxide and nitrites in PAL, is very promising for potential clinical applications.

scholarly journals Selective Apoptotic Effect of Plasma Activated Liquids on Human Cancer Cell Lines

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4254
Author(s):  
Dominika Sersenová ◽  
Zdenko Machala ◽  
Vanda Repiská ◽  
Helena Gbelcová
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Ambient Air ◽  
Cancer Cell Lines ◽  
Clinical Applications ◽  
Dermal Fibroblasts ◽  
Apoptosis Induction ◽  
Anticancer Effects ◽  
Cold Plasmas

Plasma medicine is a new field focusing on biomedical and clinical applications of cold gas plasmas, including their anticancer effects. Cold plasmas can be applied directly or indirectly as plasma-activated liquids (PAL). The effects of plasma-activated cell growth medium (PAM) and plasma-activated phosphate buffered saline (PAPBS) were tested, using a plasma pen generating streamer corona discharge in ambient air, on different cancer cell lines (melanoma A375, glioblastoma LN229 and pancreatic cancer MiaPaCa-2) and normal cells (human dermal fibroblasts HDFa). The viability reduction and apoptosis induction were detected in all cancer cells after incubation in PAL. In melanoma cells we focused on detailed insights to the apoptotic pathways. The anticancer effects depend on the plasma treatment time or PAL concentration. The first 30 min of incubation in PAL were enough to start processes leading to cell death. In fibroblasts, no apoptosis induction was observed, and only PAPBS, activated for a longer time, slightly decreased their viability. Effects of PAM and PAPBS on cancer cells showed selectivity compared to normal fibroblasts, depending on correctly chosen activation time and PAL concentration, which is very promising for potential clinical applications. This selectivity effect of PAL is conceivably induced by plasma-generated hydrogen peroxide.

scholarly journals A Triple Co-Delivery Liposomal Carrier That Enhances Apoptosis via an Intrinsic Pathway in Melanoma Cells

Cancers ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1982 ◽  
Author(s):  
Nina Filipczak ◽  
Anna Jaromin ◽  
Adriana Piwoni ◽  
Mohamed Mahmud ◽  
Can Sarisozen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Melanoma Cells ◽  
Mitochondrial Pathway ◽  
Cytotoxic Action ◽  
Cancer Therapies ◽  
Normal Cells ◽  
Freeze And Thaw ◽  
Anti Cancer ◽  
Remote Loading ◽  
Activity Mechanism

The effectiveness of existing anti-cancer therapies is based mainly on the stimulation of apoptosis of cancer cells. Most of the existing therapies are somewhat toxic to normal cells. Therefore, the quest for nontoxic, cancer-specific therapies remains. We have demonstrated the ability of liposomes containing anacardic acid, mitoxantrone and ammonium ascorbate to induce the mitochondrial pathway of apoptosis via reactive oxygen species (ROS) production by the killing of cancer cells in monolayer culture and shown its specificity towards melanoma cells. Liposomes were prepared by a lipid hydration, freeze-and-thaw (FAT) procedure and extrusion through polycarbonate filters, a remote loading method was used for dug encapsulation. Following characterization, hemolytic activity, cytotoxicity and apoptosis inducing effects of loaded nanoparticles were investigated. To identify the anticancer activity mechanism of these liposomes, ROS level and caspase 9 activity were measured by fluorescence and by chemiluminescence respectively. We have demonstrated that the developed liposomal formulations produced a high ROS level, enhanced apoptosis and cell death in melanoma cells, but not in normal cells. The proposed mechanism of the cytotoxic action of these liposomes involved specific generation of free radicals by the iron ions mechanism.

scholarly journals Selective Targeting of Cancerous Mitochondria and Suppression of Tumor Growth Using Redox-Active Treatment Adjuvant

2020 ◽  
Vol 2020 ◽  
pp. 1-30
Author(s):  
Rumiana Bakalova ◽  
Severina Semkova ◽  
Donika Ivanova ◽  
Zhivko Zhelev ◽  
Thomas Miller ◽  
...  
Keyword(s):  
Immune System ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Anticancer Drugs ◽  
Mitochondrial Membrane ◽  
Combination Drug ◽  
Normal Cells ◽  
Mitochondrial Superoxide ◽  
Anticancer Effects ◽  
Redox Active

Redox-active substances and their combinations, such as of quinone/ascorbate and in particular menadione/ascorbate (M/A; also named Apatone®), attract attention with their unusual ability to kill cancer cells without affecting the viability of normal cells as well as with the synergistic anticancer effect of both molecules. So far, the primary mechanism of M/A-mediated anticancer effects has not been linked to the mitochondria. The aim of our study was to clarify whether this “combination drug” affects mitochondrial functionality specifically in cancer cells. Studies were conducted on cancer cells (Jurkat, Colon26, and MCF7) and normal cells (normal lymphocytes, FHC, and MCF10A), treated with different concentrations of menadione, ascorbate, and/or their combination (2/200, 3/300, 5/500, 10/1000, and 20/2000 μM/μM of M/A). M/A exhibited highly specific and synergistic suppression on cancer cell growth but without adversely affecting the viability of normal cells at pharmacologically attainable concentrations. In M/A-treated cancer cells, the cytostatic/cytotoxic effect is accompanied by (i) extremely high production of mitochondrial superoxide (up to 15-fold over the control level), (ii) a significant decrease of mitochondrial membrane potential, (iii) a decrease of the steady-state levels of ATP, succinate, NADH, and NAD+, and (iv) a decreased expression of programed cell death ligand 1 (PD-L1)—one of the major immune checkpoints. These effects were dose dependent. The inhibition of NQO1 by dicoumarol increased mitochondrial superoxide and sensitized cancer cells to M/A. In normal cells, M/A induced relatively low and dose-independent increase of mitochondrial superoxide and mild oxidative stress, which seems to be well tolerated. These data suggest that all anticancer effects of M/A result from a specific mechanism, tightly connected to the mitochondria of cancer cells. At low/tolerable doses of M/A (1/100-3/300 μM/μM) attainable in cancer by oral and parenteral administration, M/A sensitized cancer cells to conventional anticancer drugs, exhibiting synergistic or additive cytotoxicity accompanied by impressive induction of apoptosis. Combinations of M/A with 13 anticancer drugs were investigated (ABT-737, barasertib, bleomycin, BEZ-235, bortezomib, cisplatin, everolimus, lomustine, lonafarnib, MG-132, MLN-2238, palbociclib, and PI-103). Low/tolerable doses of M/A did not induce irreversible cytotoxicity in cancer cells but did cause irreversible metabolic changes, including: (i) a decrease of succinate and NADH, (ii) depolarization of the mitochondrial membrane, and (iii) overproduction of superoxide in the mitochondria of cancer cells only. In addition, M/A suppressed tumor growth in vivo after oral administration in mice with melanoma and the drug downregulated PD-L1 in melanoma cells. Experimental data suggest a great potential for beneficial anticancer effects of M/A through increasing the sensitivity of cancer cells to conventional anticancer therapy, as well as to the immune system, while sparing normal cells. We hypothesize that M/A-mediated anticancer effects are triggered by redox cycling of both substances, specifically within dysfunctional mitochondria. M/A may also have a beneficial effect on the immune system, making cancer cells “visible” and more vulnerable to the native immune response.

Evaluate the Cytotoxicity of Kojic Acid Nanocomposites on Melanoma Cells and Normal Cells of the Skin

2018 ◽  
Vol 36 ◽  
pp. 45-55 ◽  
Author(s):  
Samer Hasan Hussein-Al-Ali ◽  
Palanisamy Arulselvan ◽  
Mohd Zobir Hussein ◽  
Sharida Fakurazi ◽  
Bullo Saifullah
Keyword(s):  
Skin Cancer ◽  
Cancer Cells ◽  
Kojic Acid ◽  
Normal Skin ◽  
Melanoma Cells ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Human Dermal Fibroblasts ◽  
Skin Cell ◽  
Dose Dependent

Iron oxide nanoparticles (MNPs) was synthesized by coprecipitation of Fe+2and Fe+3into highly basic media, followed by coating with chitosan (CH) and polyethylene glycol (PG) to forming CH-MNPs and PG-MNPs nanoparticles, respectively. Kojic acid (Kj) drug was loaded on the CH-MNPs and PG-MNPs nanoparticles to forming Kj-CH-MNPs and Kj-PG-MNPs nanocomposites. The potential cytotoxicity of free Kj, MNPs, Kj-CH-MNPs and Kj-PG-MNPs nanocomposites was evaluated using skin cancer cells (B16-F10 melanoma cells) and normal skin cell (Human Dermal Fibroblasts murine). Kj at concentrations in the range 1.562–50 μg/mL did not affect on the viability of normal skin cell and skin cancer cells during a 72-hours incubation. The Kj-CH-MNPs and Kj-PG-MNPs nanocomposites exhibit significant cytotoxicity in skin cancer cells in a dose-dependent manner with an IC50value 47.1 and 8.4 μg/mL, respectively.

scholarly journals Targeting Mitochondria in Melanoma

Biomolecules ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 1395
Author(s):  
Sepideh Aminzadeh-Gohari ◽  
Daniela D. Weber ◽  
Luca Catalano ◽  
René G. Feichtinger ◽  
Barbara Kofler ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Lines ◽  
Melanoma Cell ◽  
Mitochondrial Respiration ◽  
Melanoma Cells ◽  
Dermal Fibroblasts ◽  
Glycolytic Activity ◽  
Anti Cancer ◽  
Cancer Agent ◽  
Melanoma Cell Lines

Drastically elevated glycolytic activity is a prominent metabolic feature of cancer cells. Until recently it was thought that tumor cells shift their entire energy production from oxidative phosphorylation (OXPHOS) to glycolysis. However, new evidence indicates that many cancer cells still have functional OXPHOS, despite their increased reliance on glycolysis. Growing pre-clinical and clinical evidence suggests that targeting mitochondrial metabolism has anti-cancer effects. Here, we analyzed mitochondrial respiration and the amount and activity of OXPHOS complexes in four melanoma cell lines and normal human dermal fibroblasts (HDFs) by Seahorse real-time cell metabolic analysis, immunoblotting, and spectrophotometry. We also tested three clinically approved antibiotics, one anti-parasitic drug (pyrvinium pamoate), and a novel anti-cancer agent (ONC212) for effects on mitochondrial respiration and proliferation of melanoma cells and HDFs. We found that three of the four melanoma cell lines have elevated glycolysis as well as OXPHOS, but contain dysfunctional mitochondria. The antibiotics produced different effects on the melanoma cells and HDFs. The anti-parasitic drug strongly inhibited respiration and proliferation of both the melanoma cells and HDFs. ONC212 reduced respiration in melanoma cells and HDFs, and inhibited the proliferation of melanoma cells. Our findings highlight ONC212 as a promising drug for targeting mitochondrial respiration in cancer.

scholarly journals Synthesis and Characterization of FITC Labelled Ruthenium Dendrimer as a Prospective Anticancer Drug

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 411 ◽  
Author(s):  
Sylwia Michlewska ◽  
Małgorzata Kubczak ◽  
Marta Maroto-Díaz ◽  
Natalia Sanz del Olmo ◽  
Paula Ortega ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Fluorescent Probe ◽  
Chemical Sensors ◽  
Cytotoxic Effect ◽  
Fluorescein Isothiocyanate ◽  
Synthesis And Characterization ◽  
Normal Cells ◽  
Anticancer Effects ◽  
Porphyrin Core

Metallodendrimers—dendrimers with included metals—are widely investigated as biocompatible equivalents to metal nanoparticles. Applications can be expected in the fields of catalysis, as chemical sensors in molecular recognition and as anticancer drugs. Metallodendrimers can also mimic certain biomolecules, for example, haemoprotein in the case of using a dendrimer with a porphyrin core. In previous papers, we showed the promising anticancer effects of carbosilane ruthenium dendrimers. The present paper is devoted to studying biocompatibility and the cytotoxic effect on normal and cancer cells of carbosilane ruthenium dendrimers labelled with fluorescent probe fluorescein isothiocyanate (FITC). The addition of fluorescent probe allowed tracking the metallodendrimer in both normal and cancer cells. It was found that carbosilane ruthenium dendrimer labelled with FITC in concentration up to 10 µmol/L was more cytotoxic for cancer cells than for normal cells. Thus, FITC labelled carbosilane ruthenium dendrimer is a good candidate for diagnostic imaging and studying anticancer effects of metallodendrimers in cancer therapy.

scholarly journals Development of accurate temperature regulation culture system with metallic culture vessel demonstrates different thermal cytotoxicity in cancer and normal cells

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chikahiro Imashiro ◽  
Haruka Takeshita ◽  
Takashi Morikura ◽  
Shogo Miyata ◽  
Kenjiro Takemura ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Cancer Cells ◽  
Culture System ◽  
Dermal Fibroblasts ◽  
Culture Vessel ◽  
Thermal Stimulus ◽  
Culture Temperature ◽  
Hyperthermia Treatment ◽  
Normal Cells ◽  
C 30

AbstractHyperthermia has been studied as a noninvasive cancer treatment. Cancer cells show stronger thermal cytotoxicity than normal cells, which is exploited in hyperthermia. However, the absence of methods evaluating the thermal cytotoxicity in cells prevents the development of hyperthermia. To investigate the thermal cytotoxicity, culture temperature should be regulated. We, thus, developed a culture system regulating culture temperature immediately and accurately by employing metallic culture vessels. Michigan Cancer Foundation-7 cells and normal human dermal fibroblasts were used for models of cancer and normal cells. The findings showed cancer cells showed stronger thermal cytotoxicity than normal cells, which is quantitatively different from previous reports. This difference might be due to regulated culture temperature. The thermal stimulus condition (43 °C/30 min) was, further, focused for assays. The mRNA expression involving apoptosis changed dramatically in cancer cells, indicating the strong apoptotic trend. In contrast, the mRNA expression of heat shock protein (HSP) of normal cells upon the thermal stimulus was stronger than cancer cells. Furthermore, exclusively in normal cells, HSP localization to nucleus was confirmed. These movement of HSP confer thermotolerance to cells, which is consistent with the different thermal cytotoxicity between cancer and normal cells. In summary, our developed system can be used to develop hyperthermia treatment.

scholarly journals Normal Skin Cells Increase Aggressiveness of Cutaneous Melanoma by Promoting Epithelial-to-Mesenchymal Transition via Nodal and Wnt Activity

2021 ◽  
Vol 22 (21) ◽  
pp. 11719
Author(s):  
Gustavo Untiveros ◽  
Lindsay Dezi ◽  
Megan Gillette ◽  
Julia Sidor ◽  
Luigi Strizzi
Keyword(s):  
Metastatic Disease ◽  
Epithelial To Mesenchymal Transition ◽  
Cultured Cells ◽  
Normal Skin ◽  
Melanoma Cells ◽  
Dermal Fibroblasts ◽  
Successful Outcome ◽  
Normal Cells ◽  
Mesenchymal Transition ◽  
Skin Cells

Melanoma is a lethal form of skin cancer triggered by genetic and environmental factors. Excision of early-stage, poorly aggressive melanoma often leads to a successful outcome; however, left undiagnosed these lesions can progress to metastatic disease. This research investigates whether the exposure of poorly aggressive melanoma to certain normal skin cells can explain how non-metastatic melanoma becomes more aggressive while still confined to the skin. To this end, we used a serial co-culture approach to sequentially expose cells from two different, poorly aggressive human melanoma cell lines against normal cells of the skin beginning with normal melanocytes, then epidermal keratinocytes, and finally dermal fibroblasts. Protein extraction of melanoma cells occurred at each step of the co-culture sequence for western blot (WB) analysis. In addition, morphological and functional changes were assessed to detect differences between the serially co-cultured melanoma cells and non-co-cultured cells. Results show that the co-cultured melanoma cells assumed a more mesenchymal morphology and displayed a significant increase in proliferation and invasiveness compared to control or reference cells. WB analysis of protein from the co-cultured melanoma cells showed increased expression of Snail and decreased levels of E-cadherin suggesting that epithelial-to-mesenchymal transition (EMT) is occurring in these co-cultured cells. Additional WB analysis showed increased levels of Nodal protein and signaling and signs of increased Wnt activity in the co-cultured melanoma cells compared to reference cells. These data suggest that interaction between poorly aggressive melanoma cells with normal cells of the skin may regulate the transition from localized, poorly aggressive melanoma to invasive, metastatic disease via Nodal and/or Wnt induced EMT.

scholarly journals Identification of a Unique Core Domain of Par-4 Sufficient for Selective Apoptosis Induction in Cancer Cells

2003 ◽  
Vol 23 (16) ◽  
pp. 5516-5525 ◽  
Author(s):  
Nadia El-Guendy ◽  
Yanming Zhao ◽  
Sushma Gurumurthy ◽  
Ravshan Burikhanov ◽  
Vivek M. Rangnekar
Keyword(s):  
Cancer Cells ◽  
Leucine Zipper ◽  
Function Analysis ◽  
Molecular Therapy ◽  
Target Range ◽  
Nuclear Localization Sequence ◽  
Apoptosis Induction ◽  
Normal Cells ◽  
Core Domain ◽  
Leucine Zipper Domain

ABSTRACT Recent studies indicated that the leucine zipper domain protein Par-4 induces apoptosis in certain cancer cells by activation of the Fas prodeath pathway and coparallel inhibition of NF-κB transcriptional activity. However, the intracellular localization or functional domains of Par-4 involved in apoptosis remained unknown. In the present study, structure-function analysis indicated that inhibition of NF-κB activity and apoptosis is dependent on Par-4 translocation to the nucleus via a bipartite nuclear localization sequence, NLS2. Cancer cells that were resistant to Par-4-induced apoptosis retained Par-4 in the cytoplasm. Interestingly, a 59-amino-acid core that included NLS2 but not the C-terminal leucine zipper domain was necessary and sufficient to induce Fas pathway activation, inhibition of NF-κB activity, and apoptosis. Most important, this core domain had an expanded target range for induction of apoptosis, extending to previously resistant cancer cells but not to normal cells. These findings have identified a unique death-inducing domain selective for apoptosis induction in cancer cells (SAC domain) which holds promise for identifying key differences between cancer and normal cells and for molecular therapy of cancer.

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