The consequences of manipulating relaxin family peptide receptor 1 (RXFP1) level in ovarian cancer cells.

Deregulation of the relaxin family peptide system (RFPS) appears to increase the risk of range of cancers, including epithelial ovarian cancers (EOC). The present study examines the effect of relaxin family peptide receptor 1 (RXFP1) level on the biological properties of human epithelial ovarian adenocarcinoma cells (OVCAR4 and SKOV3). RXFP1 was downregulated (RXFP1↓) in the cells using the RXFP1 sgRNA CRISPR All-in-One Lentivirus set (pLenti-U6-sgRNA-SFFV-Cas9-2A-Puro), and upregulated (RXFP1↑) using the RXFP1 CRISPRa sgRNA Lentivector (pLenti-U6-sgRNA-PGK-Neo) kit, which activates the RXFP1 gene when paired with dCas9-SAM. The changes taking place during adhesion to extracellular matrix (ECM) proteins were assessed in multi-well plates coated with collagen, fibronectin, laminin and gelatin. Cellular viability was monitored based on mitochondrial metabolic activity (MTT Assay, Alamar Blue Assay) and adenosine triphosphate production (ATP Assay). The rate of cell proliferation was determined based on the percentage of Ki67 immunoreactive cells and the numbers of cells in particular cell-cycle phases. The mesenchymal-like (Boyden Chamber Assay) and amoeboid-like movements (Wound Healing Assay) of ovarian cancer cells were also analyzed after transfection. RXFP1 downregulation decreased the adhesion properties of ovarian cancer cells and increased the tendency for apoptosis under stressful conditions. In contrast, RXFP1 upregulation had pro-proliferative, pro-survival and promigratory effects. Our findings confirm that the relaxin-2/RXFP1 signaling pathway plays a role in the promotion of growth and progression of ovarian cancer.

Towards Cancer Nanoradiopharmaceuticals-Radioisotope Nanocarrier System for Prostate Cancer Theranostics Based on Radiation-Synthesized Polymer Nanogels.

Despite the tremendous development of oncology, prostate cancer remains a debilitating malignancy. One of the most promising approaches to addressing this issue is to exploit the advancements of nanomedicine in combination with well-established nuclear medicine and radiotherapy. Following this idea, we have developed a radioisotope nanocarrier platform of electron-beam-synthesized nanogels based on poly(acrylic acid). We have developed a functionalization protocol, showing the very high (>97%) efficiency of the conjugation in targeting a ligand-bombesin derivative. This engineered peptide can bind gastrin-releasing peptide receptors overexpressed in prostate cancer cells; moreover, it bears a radioisotope-chelating moiety. Our nanoplatform exhibits very promising performance in vitro; the radiolabeled nanocarriers maintained high radiochemical purity of >90% in both the labeling buffer and human serum for up to 14 days. The application of the targeted nanocarrier allowed also effective and specific uptake in PC-3 prostate cancer cells, up to almost 30% after 4 h, which is a statistically significant improvement in comparison to carrier-free radiolabeled peptides. Although our system requires further studies for more promising results in vivo, our study represents a vital advancement in radionanomedicine-one of many steps that will lead to effective therapy for castration-resistant prostate cancer.

Estrogen receptor α mediates alternariol-induced apoptosis and modulation of the invasiveness of ovarian cancer cells.

Mycotoxins are secondary metabolites of fungi that may affect both human and animal health. Some of them possess estrogenic activity, due to direct binding to estrogen receptors (ERs) and hence disturb the hormonal balance of the organism. Alternariol (AOH) was previously reported as genotoxic, estrogenic and immunomodulatory agent. However, detailed mechanism of its action has not been fully elucidated. Estrogen receptor α (ERα) was previously reported to modulate the proliferation and invasiveness of ovarian cancer cells. Thus, we decided to verify whether estrogenic-like mycotoxin may affect ovarian cancer cells via ERα. The results showed that AOH induces apoptosis and oxidative stress and that these effects are partially modulated by ERα. Moreover, AOH decreases the invasion and migration of ovarian cancer cells and promotes changes in the expression of genes and proteins that are associated with the invasiveness of cancer i.e. MMP9, SNAIL1/2, ZEB1/2, VIM, CDH1 and CDH2. In conclusion, we postulate that AOH might significantly affect the viability and invasiveness of ovarian cancer cells via modulation of ERα and therefore possibly act as an endocrine disruptive agent in ovarian cancer cells.

Revealing the Role of Alternariol in the Local Steroidogenesis in Human Prostate Normal and Cancer Cells.

The mycotoxin alternariol (AOH) can be found in food products infected by Alternaria spp. and is considered an endocrine-disruptive mycotoxin. The main mechanism of AOH toxicity is associated with DNA damage and modulation of the inflammation process. Still, AOH is considered as one of the emerging mycotoxins. In this study, we have evaluated how AOH might affect the local steroidogenesis process in the prostate, in both normal and cancer cells. We have found that AOH itself modulates the cell cycle, inflammation, and apoptosis, rather than the steroidogenesis process in prostate cancer cells; however, in the presence of another steroidogenic agent, the influence on steroidogenesis is significant. Therefore, this is the first study to report the effect of AOH on local steroidogenesis in normal and prostate cancer cells. We postulate that AOH might modulate the release of the steroid hormones and expression of the key components by interfering with the steroidogenic pathway and might be considered a steroidogenesis-altering agent.

Raman and Infrared Spectroscopy of Barium-Gallo Germanate Glasses Containing B2O3/TiO2.

Modified barium gallo-germanate glass hosts are still worthy of attention in studying structure-property relationships. In this work, two different series of glass systems based on (60-x)GeO2-xTiO2-30BaO-10Ga2O3 and (60-x)GeO2-xB2O3-30BaO-10Ga2O3 (x = 10, 30, 50 mol%) were synthesized, and their properties were studied using spectroscopic techniques. X-ray diffraction (XRD) patterns revealed that all fabricated glasses were fully amorphous material. The absorption edge shifted toward the longer wavelengths with a gradual substitution of GeO2. The spectroscopic assignments of titanium ions were performed with excitation and emission spectra compared to the additional sample containing an extremely low content of TiO2 (0.005 mol%). On the basis of Raman and FT-IR investigations, it was found that increasing the TiO2 content caused a destructive effect on the GeO4 and GeO6 structural units. The Raman spectra of a sample containing a predominantly TiO2 (50 mol%) proved that the band was located near 650 cm-1, which corresponded to the stretching vibration of Ti-O in TiO6 unit. The deconvoluted IR results showed that the germanate glass network consisted of the coexistence of two BO3 and BO4 structural groups. Based on the experimental investigations, we concluded that the developed materials are a promising candidate for use as novel glass host matrices for doping rare-earth and/or transition metal ions.

Effect of the mycotoxin deoxynivalenol in combinational therapy with TRAIL on prostate cancer cells.

Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) is reported as a promising anti-cancer therapeutic target. Unfortunately, prostate cancer cells (PCa) are partially resistant to TRAIL-induced apoptosis limiting its therapeutic potential. The existing body of knowledge suggests that naturally produced compounds, such as mycotoxin deoxynivalenol (DON), might potentially sensitize cells to TRAIL treatment and improve the efficiency of therapy. Previously, we observed that DON induces oxidative stress and apoptosis in PCa cell lines. Thus we addressed here whether DON can sensitize PCa cells to TRAIL-induced apoptosis. Our data demonstrates that three out of four tested PCa cell lines pretreated with DON increased TRAIL-induced apoptosis detected with flow cytometry. This effect was associated with oxidative stress (LNCaP and DU-145 cell line) and elevated DNA damage (DU-145, LNCaP, and 22Rv1 cell lines). Next, in the animal model we inoculated PC tumor to SCKID mice followed by administration of DON intraperitoneally and/or TRIAL intravenously. During 21 days monitoring of tumor growth, the animals received 7 doses of DON, TRAIL, DON+TRAIL or control injections. No significant reduction in tumor mass was observed after combinational treatment of TRAIL and DON compared to 1 µg/kg of body weight DON treatment alone, which itself decreased the tumor growth. However, despite the lack of the TRAIL + DON effect, DON itself inducing apoptosis is an interesting compound worth investigating in the context of other combination therapies.

Magnetocaloric performance of the three-component Ho1-xErxNi2 (x = 0.25, 0.5, 0.75) Laves phases as composite refrigerants.

To date, significant efforts have been put into searching for materials with advanced magnetocaloric properties which show promise as refrigerants and permit realization of efficient cooling. The present study, by an example of Ho1-xErxNi2, develops the concept of magnetocaloric efficiency in the rare-earth Laves-phase compounds. Based on the magneto-thermodynamic properties, their potentiality as components of magnetocaloric composites is illustrated. The determined regularities in the behaviour of the heat capacity, magnetic entropy change, and adiabatic temperature change of the system substantiate reaching high magnetocaloric potentials in a desired temperature range. For the Ho1-xErxNi2 solid solutions, we simulate optimal molar ratios and construct the composites used in magnetic refrigerators performing an Ericsson cycle at low temperatures. The tailored magnetocaloric characteristics are designed and efficient procedures for their manufacturing are developed. Our calculations based on the real empirical data are very promising and open avenue to further experimental studies. Systems showing large magnetocaloric effect (MCE) at low temperatures are of importance due to their potential utilization in refrigeration for gas liquefaction.

Near-IR Luminescence of Rare-Earth Ions (Er3+, Pr3+, Ho3+, Tm3+) in Titanate-Germanate Glasses under Excitation of Yb3.

Inorganic glasses co-doped with rare-earth ions have a key potential application value in the field of optical communications. In this paper, we have fabricated and then characterized multicomponent TiO2-modified germanate glasses co-doped with Yb3+/Ln3+ (Ln = Pr, Er, Tm, Ho) with excellent spectroscopic properties. Glass systems were directly excited at 980 nm (the 2F7/2 → 2F5/2 transition of Yb3+). We demonstrated that the introduction of TiO2 is a promising option to significantly enhance the main near-infrared luminescence bands located at the optical telecommunication window at 1.3 µm (Pr3+: 1G4 → 3H5), 1.5 µm (Er3+: 4I13/2 → 4I15/2), 1.8 µm (Tm3+: 3F4 → 3H6) and 2.0 µm (Ho3+: 5I7 → 7I8). Based on the lifetime values, the energy transfer efficiencies (ηET) were estimated. The values of ηET are changed from 31% for Yb3+/Ho3+ glass to nearly 53% for Yb3+/Pr3+ glass. The investigations show that obtained titanate-germanate glass is an interesting type of special glasses integrating luminescence properties and spectroscopic parameters, which may be a promising candidate for application in laser sources emitting radiation and broadband tunable amplifiers operating in the near-infrared range.

Bladder Cancer Cells Exert Pleiotropic Effects on Human Adipose-Derived Stem Cells.

Stem cell-based therapies are considered one of the most promising disciplines in biomedicine. Bladder cancer patients could benefit from therapies directed to promote healing after invasive surgeries or to lessen urinary incontinence, a common side effect of both cancer itself and the treatment. However, the local delivery of cells producing large amounts of paracrine factors may alter interactions within the microenvironment. For this reason, reconstructive cellular therapies for patients with a history of cancer carry a potential risk of tumor reactivation. We used an indirect co-culture model to characterize the interplay between adipose-derived stem cells and bladder cancer cells. Incubation with ASCs increased MCP-1 secretion by bladder cancer cells (from 2.1-fold to 8.1-fold, depending on the cell line). Cancer cell-derived factors altered ASC morphology. Cells with atypical shapes and significantly enlarged volumes appeared within the monolayer. Incubation in a conditioned medium (CM) containing soluble mediators secreted by 5637 and HB-CLS-1 bladder cancer cell lines decreased ASC numbers by 47.5% and 45.7%. A significant increase in adhesion to ECM components, accompanied by reduced motility and sheet migration, was also observed after incubation in CM from 5637 and HB-CLS-1 cells. No differences were observed when ASCs were co-cultured with HT-1376 cells. Our previous and present results indicate that soluble mediators secreted by ASCs and bladder cancer cells induce opposite effects influencing cells that represent the non-muscle-invasive urinary bladder.

Spectroscopic Properties of Pr3+, Tm3+, and Ho3+ in Germanate-Based Glass Systems Modified by TiO2.

In this paper, the effect of the GeO2:TiO2 molar ratio in glass composition on the spectroscopic properties of germanate glasses was systematically investigated. The visible luminescence bands associated with characteristic 1D2 → 3H4 (red), 5S2, 5F4 → 5I8 (green), and 1D2 → 3F4 (blue) transitions of Pr3+, Ho3+, and Tm3+ ions in systems modified by TiO2 were well observed, respectively. It was found that the luminescence intensity of glasses containing Pr3+ and Ho3+ ions increases, whereas, for Tm3+-doped systems, luminescence quenching with increasing content of TiO2 was observed. Based on Commission Internationale de I'Eclairage (CIE) chromaticity coordinates (x, y) analysis, it was demonstrated that the value of chromaticity coordinates for all glasses depends on the GeO2:TiO2 molar ratio. The addition of TiO2 to system compositions doped with Tm3+ ions shifts the (x, y) to the center of the CIE diagram. However, chromaticity coordinates evaluated for glasses containing Pr3+ ions move to a purer red color. Our results confirm that the spectroscopic properties of the studied glasses strongly depend on TiO2 content. Moreover, it can be stated that germanate-based glass systems modified by TiO2 can be used for optoelectronics in RGB technology as red (Pr3+), green (Ho3+), and blue (Tm3+) emitters.

Deoxynivalenol induces apoptosis and autophagy in human prostate epithelial cells via PI3K/Akt signaling pathway.

Phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway is one of the most deregulated signaling pathway in prostate cancer. It controls basic processes in cells: cell proliferation and death. Any disturbances in the balance between cell death and survival might result in carcinogenesis. Deoxynivalenol (DON) is one of the most common mycotoxins, a toxic metabolites of fungi, present in our everyday diet and feed. Although previous studies reported DON to induce oxidative stress, modulate steroidogenesis, DNA damage and cell cycle modulation triggering together its toxicity, its effect on normal prostate epithelial cells is not known. The aim of the study was to evaluate the effect of DON on the apoptosis and autophagy in normal prostate epithelial cells via modulation of PI3K/Akt signaling pathway. The results showed that DON in a dose of 30 µM and 10 µM induces oxidative stress, DNA damage and cell cycle arrest in G2/M cell cycle phase. The higher concentration of DON induces apoptosis, whereas lower one autophagy in PNT1A cells, indicating that modulation of PI3K/Akt by DON results in the induction of autophagy triggering apoptosis in normal prostate epithelial cells.

Transition Metals (Cr3+) and Lanthanides (Eu3+) in Inorganic Glasses with Extremely Different Glass-Formers B2O3 and GeO2.

Glasses containing two different network-forming components and doped with optically active ions exhibit interesting properties. In this work, glass systems based on germanium dioxide and boron trioxide singly doped with lanthanides (Eu3+) and transition metals (Cr3+) ions are research subjects. Optical spectroscopy was the major research tool used to record excitation and emission spectra in a wide spectral range for studied systems. The emitted radiation of glasses doped with Cr3+ ions is dominated by broadband luminescence centered at 770 nm and 1050 nm (4T2 → 4A2). Interestingly, the increase of concentration of one of the oxides contributed to the detectable changes of the R-line (2E → 4A2) of Cr3+ ions. Moreover, EPR spectroscopy confirmed the paramagnetic properties of the obtained glasses. The influence of molar ratio GeO2:B2O3 on spectroscopic properties for Eu3+ ions is discussed. The intensity of luminescence bands due to transitions of trivalent europium ions as well as the ratio R/O decrease with the increase of B2O3. On the other hand, the increase in concentration B2O3 influences the increasing tendency of luminescence lifetimes for the 5D0 state of Eu3+ ions. The results will contribute to a better understanding of the role of the glass host and thus the prospects for new optical materials.

Injecting drug users, MSM and people at the older age should be routinely tested for HCV in Poland - data derived from a post-exposure prophylaxis population.

OBJECTIVE: The aim of the study was to identify risk factors for HCV infection and thus identify groups for routine HCV testing in the group of people consulted for post-exposure prophylaxis (PEP). MATERIAL AND METHODS: A retrospective analysis was performed of cross-sectional data available from consultations due to post-exposure prophylaxis in HIV Out-patient Clinic and Emergency Department (ED) of Hospital for Infectious Diseases in Warsaw, Poland. Data were obtained from the electronic database, from 2008-o 2016. For statistical analysis, χ2 and t-tests were used for group comparisons, as appropriate. A total of 3,593 persons were included in the study, 60 (1.7%) were anti-HCV positive. In the first step, univariate models were estimated for each of predictors separately. RESULTS: The results showed that odds of infection are significantly higher in males (OR = 1.92), people after non-professional exposure (OR = 3.82), and increase with age (OR = 1.03). In the next step, a multivariate logistic model was fitted in the group of participants after non-professional exposure with gender, age, and route of exposure as predictors. Obtained results revealed significantly higher odds of infection, both in IDU (OR = 162.6) and gender exposure (OR = 3.59) groups. After including routes of exposure, effects of age remained significant (OR = 1.05), while the effects of gender did not (OR = 1.12). CONCLUSIONS: Based on the study results, it is recommended that routine testing for HCV should be provided for people at older age, and for individual with behavioural risk factors, such as history of injecting drus use or sexual exposure, particularly among men having sex with men (MSM).

Estrogen Receptor ß Participates in Alternariol-Induced Oxidative Stress in Normal Prostate Epithelial Cells.

Alternaria toxins are considered as emerging mycotoxins, however their toxicity has not been fully evaluated in humans. Alternariol (AOH), the most prevalent Alternaria mycotoxin, was previously reported to be genotoxic and to affect hormonal balance in cells; however, its direct molecular mechanism is not known. The imbalance in androgen/estrogen ratio as well as chronic inflammation are postulated as factors in prostate diseases. The environmental agents affecting the hormonal balance might participate in prostate carcinogenesis. Thus, this study evaluated the effect of two doses of AOH on prostate epithelial cells. We observed that AOH in a dose of 10 µM induces oxidative stress, DNA damage and cell cycle arrest and that this effect is partially mediated by estrogen receptor ß (ERß) whereas the lower tested dose of AOH (0.1 µM) induces only oxidative stress in cells. The modulation of nuclear erythroid-related factor 2 (Nrf2) was observed in response to the higher dose of AOH. The use of selective estrogen receptor ß (ERß) inhibitor PHTPP revealed that AOH-induced oxidative stress in both tested doses is partially dependent on activation of ERß, but lack of its activation did not protect cells against AOH-induced ROS production or DNA-damaging effect in case of higher dose of AOH (10 µM). Taken together, this is the first study reporting that AOH might affect basic processes in normal prostate epithelial cells associated with benign and malignant changes in prostate tissue.

FOXO3a and Its Regulators in Prostate Cancer.

Forkhead box O3 (FOXO3a) is a member of a subfamily of forkhead transcription factors involved in the basic processes within a cell, including proliferation, apoptosis, cell cycle regulation, and DNA damage. As a transcription factor, FOXO3a is involved in the response to cellular stress, UV radiation, or oxidative stress. Its regulation is based on the modification of proteins as well as regulation by other proteins, e.g., growth factors. FOXO3a is commonly deregulated in cancer cells, and its inactivation is associated with initiation and progression of tumorigenesis, suggesting its role as a tumor suppressor; however, its role is still disputed and seems to be dependent on upstream signaling. Nevertheless, FOXO3a serves as an interesting potential target in therapies as it is regulated during treatment with very common anti-cancer drugs such as paclitaxel, cisplatin, docetaxel, and doxorubicin. This review aims to update the reported role of FOXO3a in prostate cancer (PCa), with a focus on its regulators that might serve as potential therapeutic agents in PCa therapy.

In Vitro Analysis of Deoxynivalenol Influence on Steroidogenesis in Prostate.

Deoxynivalenol (DON) is a type-B trichothecene mycotoxin produced by Fusarium species, reported to be the most common mycotoxin present in food and feed products. DON is known to affect the production of testosterone, follicle stimulating hormone (FSH) and luteinizing hormone (LH) in male rats, consequently affecting reproductive endpoints. Our previous study showed that DON induces oxidative stress in prostate cancer (PCa) cells, however the effect of DON on the intratumor steroidogenesis in PCa and normal prostate cells was not investigated. In this study human normal (PNT1A) and prostate cancer cell lines with different hormonal sensitivity (PC-3, DU-145, LNCaP) were exposed to DON treatment alone or in combination with dehydroepiandrosterone (DHEA) for 48 h. The results of the study demonstrated that exposure to DON alone or in combination with DHEA had a stimulatory effect on the release of estradiol and testosterone and also affected progesterone secretion. Moreover, significant changes were observed in the expression of genes related to steroidogenesis. Taken together, these results indicate that DON might affect the process of steroidogenesis in the prostate, demonstrating potential reproductive effects in humans.

Angiotensin II and Angiotensin Receptors 1 and 2-Multifunctional System in Cells Biology, What Do We Know?

For years, the renin-angiotensin system (RAS) has been perceived as a system whose role is to primarily modulate the functioning of the cardiovascular system. Years of research into the role of RAS have provided the necessary data to confirm that the role of RAS is very complex and not limited to the cardiovascular system. The presence of individual elements of the renin-angiotensin (RA) system allows to control many processes, ranging from the memorization to pro-cancer processes. Maintaining the proportions between the individual axes of the RA system allows for achieving a balance, often called homeostasis. Thus, any disturbance in the expression or activity of individual RAS elements leads to pathophysiological processes.

Nrf2: a main responsive element in cells to mycotoxin-induced toxicity.

Nuclear factor erythroid 2-like 2 (Nrf2) is a transcription factor participating in response to cellular oxidative stress to maintain the redox balance. Generation of reactive oxygen species (ROS) and, in consequence, oxidative stress, are physiological as well as pathological processes which take place in almost all types of cells. Nrf2, in response to oxidative stress, activates expression and production of antioxidant enzymes to remove free radicals. However, the role of Nrf2 seems to be more sophisticated and its increased expression observed in cancer cells allows to draw a conclusion that its role is tissue-and condition-dependent. Interestingly, Nrf2 might also play a crucial role in response to environmental factors like mycotoxins. Thus, the aim of the study is to review the role of Nrf2 in cells exposed to most common mycotoxins to check if the Nrf2 signaling pathway serves as the main response element to mycotoxin-induced oxidative stress in human and animal cells and if it can be a target of detoxifying agents.

Mycotoxin Alternariol (AOH) Affects Viability and Motility of Mammary Breast Epithelial Cells.

Mycotoxins are present in everyday diet as common food and feed pollutants. A part of them is still concerned as so-called emerging mycotoxins. Due to the lack of toxicity data, the safety limits and detail molecular mechanism have been not established yet for all of them. Alternariol (AOH), as one of these mycotoxins, produced by Alternaria species, is so far reported as an estrogenic, genotoxic, and immunomodulatory agent; however, its direct effect on human health is not known. Especially, in the case of hormone-dependent tissues which are sensitive to both endogenic, as well as external estrogenic agents, it might be crucial to assess the effect of AOH. Thus, this study evaluated how exposure to AOH affects viability and motility of the human normal mammary gland epithelial in vitro model. We observed that AOH significantly affects viability of cells in a time- and dose-dependent manner. Moreover, the induction of oxidative stress, DNA damage, and cell cycle arrest in the G2/M cell cycle phase was observed. The motility of 184A1 cells was also significantly affected. On the molecular level, AOH induced antioxidative stress response via activation of Nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway agents, as well as decrease in the phosphorylation of protein kinase B (Akt) and p44/42 (ERK 1-2) molecules, indicating that AOH might affect crucial signaling pathways in both physiological and pathophysiological processes in breast tissue.

Methylsulfonylmethane sensitizes endometrial cancer cells to doxorubicin.

BACKGROUND: Methylsulfonylmethane (MSM) is a commonly used diet supplement believed to decrease the inflammation in joints and fastens recovery in osteoarthritis, gastric mucosal injury, or obesity-related disorders. It was also suggested that MSM might play a beneficial role in cancer treatment. PURPOSE: So far, the MSM might have a potentially beneficial effect in endometrial cancer (EC) treatment. STUDY DESIGN: This study evaluated the effect and usefulness of MSM in combinatory therapy with known drug doxorubicin (DOX). METHODS: The effect of combinational treatment of MSM and DOX on the induction of apoptosis was evaluated in EC cell lines (ISHIKAWA, MFE-296, MFE-280). RESULTS: We observed that MSM itself induces apoptosis in EC cell lines, and pre-treatment with MSM for 24 h increases the sensitivity of EC cells to DOX-induced apoptosis and DNA damage and that effect might be regulated by p42/44 (Erk1/2) MAPK and Akt (protein kinase B). CONCLUSION: These results for the first time show that MSM might act as a sensitizer of EC cells to known drugs, for which EC cells quickly acquire resistance. Graphical abstract.