Landscape of Endometrial Cancer: Molecular Mechanisms, Biomarkers, and Target Therapy.

Endometrial cancer is one the most prevalent gynecological cancers and, unfortunately, has a poor prognosis due to low response rates to traditional treatments. However, the progress in molecular biology and understanding the genetic mechanisms involved in tumor processes offers valuable information that has led to the current classification that describes four molecular subtypes of endometrial cancer. This review focuses on the molecular mechanisms involved in the pathogenesis of endometrial cancers, such as genetic mutations, defects in the DNA mismatch repair pathway, epigenetic changes, or dysregulation in angiogenic or hormonal signaling pathways. The preclinical genomic and molecular investigations presented allowed for the identification of some molecules that could be used as biomarkers to diagnose, predict, and monitor the progression of endometrial cancer. Besides the therapies known in clinical practice, targeted therapy is described as a new cancer treatment that involves identifying specific molecular targets in tumor cells. By selectively inhibiting these targets, key signaling pathways involved in cancer progression can be disrupted while normal cells are protected. The connection between molecular biomarkers and targeted therapy is vital in the fight against cancer. Ongoing research and clinical trials are exploring the use of standard therapy agents in combination with other treatment strategies like immunotherapy and anti-angiogenesis therapy to improve outcomes and personalize treatment for patients with endometrial cancer. This approach has the potential to transform the management of cancer patients. In conclusion, enhancing molecular tools is essential for stratifying the risk and guiding surgery, adjuvant therapy, and cancer treatment for women with endometrial cancer. In addition, the information from this review may have an essential value in the personalized therapy approach for endometrial cancer to improve the patient's life.

Synthesis of 1,3,4-Thiadiazole Derivatives and Their Anticancer Evaluation.

Thiadiazole derivatives have garnered significant attention in the field of medicinal chemistry due to their diverse pharmacological activities, including anticancer properties. This article presents the synthesis of a series of thiadiazole derivatives and investigates their chemical characterization and potential anticancer effects on various cell lines. The results of the nuclear magnetic resonance (NMR) analyses confirmed the successful formation of the target compounds. The anticancer potential was evaluated through in silico and in vitro cell-based assays using LoVo and MCF-7 cancer lines. The assays included cell viability, proliferation, apoptosis, and cell cycle analysis to assess the compounds' effects on cancer cell growth and survival. Daphnia magna was used as an invertebrate model for the toxicity evaluation of the compounds. The results revealed promising anticancer activity for several of the synthesized derivatives, suggesting their potential as lead compounds for further drug development. The novel compound 2g, 5-[2-(benzenesulfonylmethyl)phenyl]-1,3,4-thiadiazol-2-amine, demonstrated good anti-proliferative effects, exhibiting an IC50 value of 2.44 µM against LoVo and 23.29 µM against MCF-7 after a 48-h incubation and little toxic effects in the Daphnia test.

Cell Culture Model Evolution and Its Impact on Improving Therapy Efficiency in Lung Cancer.

Optimizing cell culture conditions is essential to ensure experimental reproducibility. To improve the accuracy of preclinical predictions about the response of tumor cells to different classes of drugs, researchers have used 2D or 3D cell cultures in vitro to mimic the cellular processes occurring in vivo. While 2D cell culture provides valuable information on how therapeutic agents act on tumor cells, it cannot quantify how the tumor microenvironment influences the response to therapy. This review presents the necessary strategies for transitioning from 2D to 3D cell cultures, which have facilitated the rapid evolution of bioengineering techniques, leading to the development of microfluidic technology, including organ-on-chip and tumor-on-chip devices. Additionally, the study aims to highlight the impact of the advent of 3D bioprinting and microfluidic technology and their implications for improving cancer treatment and approaching personalized therapy, especially for lung cancer. Furthermore, implementing microfluidic technology in cancer studies can generate a series of challenges and future perspectives that lead to the discovery of new predictive markers or targets for antitumor treatment.

Synthesis, Characterization and Cytotoxic Evaluation of New Pyrrolo[1,2-b]pyridazines Obtained via Mesoionic Oxazolo-Pyridazinones.

New pyrrolo[1,2-b]pyridazines were synthesized by 3 + 2 cycloaddition reaction between mesoionic oxazolo-pyridazinones and methyl/ethyl propiolate. The mesoionic compounds were generated in situ by action of acetic anhydride on 3(2H)pyridazinone acids obtained from corresponding esters by alkaline hydrolysis followed by acidification. The structures of the compounds were confirmed by elemental analyses and IR, 1H-NMR, 13C-NMR, and X-ray diffraction data. The regioselectivity of cycloaddition was evidenced by NMR spectroscopy and confirmed by X-ray analysis. The compounds were evaluated for their cytotoxicity on plant cells (Triticum aestivum L.) and crustacean animal cells (Artemia franciscana Kellogg and Daphnia magna Straus). The results indicated that the tested compounds exhibited low toxicity on the plant cell (IC50 values higher than 200 µM), while on Artemia nauplii no lethality was observed. Daphnia magna assay showed that pyrrolo[1,2-b]pyridazines 5a and 5c could exhibit toxic effects, whereas, for the other compounds, toxicity was low to moderate. Also, the cytotoxic effects of the compounds were tested on three human adenocarcinoma-derived adherent cell lines (colon LoVo, ovary SK-OV-3, breast MCF-7). The in vitro compound-mediated cytotoxicity assays, performed by the MTS technique, demonstrated dose- and time-dependent cytotoxic activity for several compounds, the highest anti-tumor activity being observed for 5a, 2c, and 5f, especially against colon cancer cells.

Polygonum cuspidatum Loaded Nanostructured Lipid Carriers for Dual Inhibition of TNF-α- and IL-6 Cytokines and Free Radical Species.

The main objective of this study was the testing of natural compounds, such as Polygonum cuspidatum (PgnC) loaded into nanostructured lipid carriers (NLC), which can act as a "double-edged sword" aimed at simultaneously combating dangerous free radicals and inhibiting pro-inflammatory cytokines. Resveratrol-rich PgnC extract was paired with another phytochemical, Diosgenin (DSG), in NLC. The lipid nanocarriers carrying both herbals (NLC-DSG-PgnC) had spherical diameters (100 ± 2 50 nm), a polydispersity index of ~0.15, and electrokinetic potentials greater than -46.5 mV. Entrapment efficiencies of 65% for PgnC and 87% for DSG were determined by chromatographic and UV-Vis spectroscopy assays. Cell cytotoxicity analysis proved that 50 µg/mL of NLC-PgnC and dual-NLC ensured a biocompatible effect like the untreated cells. The dual-NLC assured a much slower in vitro release of DSG and PgnC (67% PgnC and 48% DSG) than the individual-NLC (78% PgnC and 47% DSG) after 4 h of experiments. NLC encapsulating PgnC presented a superior ability to capture cationic radicals: 74.5 and 77.9%. The chemiluminescence results pointed out the non-involvement of DSG in stopping oxygenated free radicals, while the antioxidant activity was maintained at a level higher than 97% for dual-NLC. NLC-DSG-PgnC ensured a promising capacity for inhibition of pro-inflammatory cytokine IL-6, ranging from 91.9 to 94.9%.

Novel Bovine Serum Albumin-Decorated-Nanostructured Lipid Carriers Able to Modulate Apoptosis and Cell-Cycle Response in Ovarian, Breast, and Colon Tumoral Cells.

A novel nanoscale approach was developed for the improved cellular internalization of hybrid bovine serum albumin-lipid nanocarriers loaded with piperine (NLC-Pip-BSA) in different tumor cells. The effect of the BSA-targeted-NLC-Pip and untargeted-NLC-Pip on the viability, proliferation, and levels of cell-cycle damage and apoptosis in the colon (LoVo), ovarian (SKOV3) and breast (MCF7) adenocarcinoma cell lines was comparatively discussed. NLCs were characterized concerning particle size, morphology, zeta potential, phytochemical encapsulation efficiency, ATR-FTIR, and fluorescence spectroscopy. The results showed that NLC-Pip-BSA showed a mean size below 140 nm, a zeta potential of -60 mV, and an entrapment efficiency of 81.94% for NLC-Pip and 80.45% for NLC-Pip-BSA. Fluorescence spectroscopy confirmed the coating of the NLC with the albumin. By MTS and RTCA assays, NLC-Pip-BSA showed a more pronounced response against the LoVo colon cell line and MCF-7 breast tumor cell lines than against the ovarian SKOV-3 cell line. Flow cytometry assay demonstrated that the targeted NLC-Pip had more cytotoxicity and improved apoptosis than the untargeted ones in MCF-7 tumor cells (p < 0.05). NLC-Pip caused a significant increase in MCF-7 breast tumor cell apoptosis of ~8X, while NLC-Pip-BSA has shown an 11-fold increase in apoptosis.

A Study on Repositioning Nalidixic Acid via Lanthanide Complexation: Synthesis, Characterization, Cytotoxicity and DNA/Protein Binding Studies.

"Drug repositioning" is a modern strategy used to uncover new applications for out-of-date drugs. In this context, nalidixic acid, the first member of the quinolone class with limited use today, has been selected to obtain nine new metal complexes with lanthanide cations (La3+, Sm3+, Eu3+, Gd3+, Tb3+); the experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms, findings that are supported by DFT calculations. The cytotoxic activity of the complexes has been studied using the tumoral cell lines, MDA-MB-231 and LoVo, and a normal cell line, HUVEC. The most active compounds of the series display selective activity against LoVo. Their affinity for DNA and the manner of binding have been tested using UV-Vis spectroscopy and competitive binding studies; our results indicate that major and minor groove binding play a significant role in these interactions. The affinity towards serum proteins has also been evaluated, the complexes displaying higher affinity towards albumin than apotransferrin.

New Pyrrole Derivatives as Promising Biological Agents: Design, Synthesis, Characterization, In Silico, and Cytotoxicity Evaluation.

The current study describes the synthesis, physicochemical characterization and cytotoxicity evaluation of a new series of pyrrole derivatives in order to identify new bioactive molecules. The new pyrroles were obtained by reaction of benzimidazolium bromide derivatives with asymmetrical acetylenes in 1,2-epoxybutane under reflux through the Huisgen [3 + 2] cycloaddition of several ylide intermediates to the corresponding dipolarophiles. The intermediates salts were obtained from corresponding benzimidazole with bromoacetonitrile. The structures of the newly synthesized compounds were confirmed by elemental analysis, spectral techniques (i.e., IR, 1H-NMR and 13C-NMR) and single-crystal X-ray analysis. The cytotoxicity of the synthesized compounds was evaluated on plant cells (i.e., Triticum aestivum L.) and animal cells using aquatic crustaceans (i.e., Artemia franciscana Kellogg and Daphnia magna Straus). The potential antitumor activity of several of the pyrrole derivatives was studied by performing in vitro cytotoxicity assays on human adenocarcinoma-derived cell lines (i.e., LoVo (colon), MCF-7 (breast), and SK-OV-3 (ovary)) and normal human umbilical vein endothelial cells (HUVECs). The obtained results of the cytotoxicity assessment indicated that the tested compounds had nontoxic activity on Triticum aestivum L., while on Artemia franciscana Kellogg nauplii, only compounds 2c and 4c had moderate toxicity. On Daphnia magna, 4b and 4c showed high toxicity; 2a, 2b, and 2c moderate to high toxicity; only 4a and 4d were nontoxic. The compound-mediated cytotoxicity assays showed that several pyrrole compounds demonstrated dose- and time-dependent cytotoxic activity against all tested tumor cell lines, the highest antitumor properties being achieved by 4a and its homologue 4d, especially against LoVo colon cells.

Challenges in Coopted Hydrophilic and Lipophilic Herbal Bioactives in the Same Nanostructured Carriers for Effective Bioavailability and Anti-Inflammatory Action.

There is ongoing research on various herbal bioactives and delivery systems which indicates that both lipid nanocarriers and herbal medicines will be fine tunned and integrated for future bio-medical applications. The current study was undertaken to systematically develop NLC-DSG-yam extract for the improved efficacy of herbal Diosgenin (DSG) in the management of anti-inflammatory disorders. NLCs were characterized regarding the mean size of the particles, morphological characteristics, physical stability in time, thermal behaviour, and entrapment efficiency of the herbal bioactive. Encapsulation efficiency and in vitro antioxidant activity measured the differences between the individual and dual co-loaded-NLC, the co-loaded one assuring a prolonged controlled release of DSG and a more emphasized ability of capturing short-life reactive oxygen species (ROS). NLCs safety properties were monitored following the in vitro MTS ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay) and RTCA (Real-Time Cell Analysis) assays. Concentrations less than 50 µg/mL showed no cytotoxic effects during in vitro cytotoxicity assays. Besides, the NLC-DSG-yam extract revealed a great anti-inflammatory effect, as the production of pro-inflammatory cytokines (TNF-alpha, IL-6) was significantly inhibited at 50 µg/mL NLC (e.g., 98.2% ± 1.07 inhibition of TNF-α, while for IL-6 the inhibition percentage was of 62% ± 1.07). Concluding, using appropriate lipid nanocarriers, the most desirable properties of herbal bioactives could be improved.

Multifaced Role of Dual Herbal Principles Loaded-Lipid Nanocarriers in Providing High Therapeutic Efficacity.

Although many phytochemicals have been used in traditional medicine, there is a great need to refresh the health benefits and adjust the shortcomings of herbal medicine. In this research, two herbal principles (Diosgenin and Glycyrrhiza glabra extract) coopted in the Nanostructured Lipid Carriers have been developed for improving the most desirable properties of herbal medicine-antioxidant and anti-inflammatory actions. The contribution of phytochemicals, vegetable oils and of lipid matrices has been highlighted by comparative study of size, stability, entrapment efficiency, morphological characteristics, and thermal behavior. According to the in vitro MTS and RTCA results, the dual herbal-NLCs were no cytotoxic toward endothelial cells at concentrations between 25 and 100 µg/mL. A rapid release of Glycyrrhiza glabra and a motivated delay of Diosgenin was detected by the in vitro release experiments. Dual herbal-NLCs showed an elevated ability to annihilate long-life cationic radicals (ABTS•+) and short-life oxygenated radicals (an inhibition of 63.4% ABTS•+, while the ability to capture radical oxygen species reached 96%). The production of pro-inflammatory cytokines was significantly inhibited by the newly herbals-NLC (up to 97.9% inhibition of TNF-α and 62.5% for IL-6). The study may open a new pharmacotherapy horizon; it provides a comprehensive basis for the use of herbal-NLC in the treatment of inflammatory diseases.

Resveratrol Modulation of Apoptosis and Cell Cycle Response to Cisplatin in Head and Neck Cancer Cell Lines.

In head and neck cancers, the effectiveness of cisplatin (CisPt) treatment is limited by its toxicity, especially when higher doses are necessary, and the possible occurrence of cisplatin resistance. This study evaluated the effects of resveratrol (RSV) on the expression of different genes involved in the response of human tumor cells (FaDu, PE/CA-PJ49) to cisplatin therapy. Our results revealed that RSV induced apoptosis amplification in both FaDu and PE/CA-PJ49 cells and modulated the expression of specific genes differently than in normal HaCaT cells. In FaDu cells, combined CisPt + RSV treatment induced an increase in apoptosis, which was associated with an increase in c-MYC and TP53 and a decrease in BCL-2 expression. While CisPt + RSV treatment induced apoptosis in PE/CA-PJ49 cells by inhibition of BCL-2 associated with high levels of MDM-2 and subsequently led to inhibition of TP53 gene expression. Decreased c-MYC expression in PE/CA-PJ49 treated with CisPt + RSV was accompanied by cell cycle blockage in G0/G1 phase. In conclusion, RSV influences tumor cell response to CisPt by inducing apoptosis and modulating gene expression. In addition, in normal HaCaT cells, RSV was able to reduce the harmful effects of CisPt.

Synthesis and Anticancer Evaluation of New 1,3,4-Oxadiazole Derivatives.

In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of new 2,5-diaryl/heteroaryl-1,3,4-oxadiazoles were designed and synthesized. The structures of the new compounds were established using elemental analyses, IR and NMR spectral data. The compounds were evaluated for their anticancer potential on two standardized human cell lines, HT-29 (colon adenocarcinoma) and MDA-MB-231 (breast adenocarcinoma). Cytotoxicity was measured by MTS assay, while cell cycle arrest and apoptosis assays were conducted using a flow cytometer, the results showing that the cell line MDA-MB-231 is more sensitive to the compounds' action. The results of the predictive studies using the PASS application and the structural similarity analysis indicated STAT3 and miR-21 as the most probable pharmacological targets for the new compounds. The promising effect of compound 3e, 2-[2-(phenylsulfanylmethyl)phenyl]-5-(4-pyridyl)-1,3,4-oxadiazole, especially on the MDA-MB-231 cell line motivates future studies to improve the anticancer profile and to reduce the toxicological risks. It is worth noting that 3e produced a low toxic effect in the D. magna 24 h assay and the predictive studies on rat acute toxicity suggest a low degree of toxic risks.

Rare-Earth Metal Complexes of the Antibacterial Drug Oxolinic Acid: Synthesis, Characterization, DNA/Protein Binding and Cytotoxicity Studies.

"Drug repositioning" is a current trend which proved useful in the search for new applications for existing, failed, no longer in use or abandoned drugs, particularly when addressing issues such as bacterial or cancer cells resistance to current therapeutic approaches. In this context, six new complexes of the first-generation quinolone oxolinic acid with rare-earth metal cations (Y3+, La3+, Sm3+, Eu3+, Gd3+, Tb3+) have been synthesized and characterized. The experimental data suggest that the quinolone acts as a bidentate ligand, binding to the metal ion via the keto and carboxylate oxygen atoms; these findings are supported by DFT (density functional theory) calculations for the Sm3+ complex. The cytotoxic activity of the complexes, as well as the ligand, has been studied on MDA-MB 231 (human breast adenocarcinoma), LoVo (human colon adenocarcinoma) and HUVEC (normal human umbilical vein endothelial cells) cell lines. UV-Vis spectroscopy and competitive binding studies show that the complexes display binding affinities (Kb) towards double stranded DNA in the range of 9.33 × 104 - 10.72 × 105. Major and minor groove-binding most likely play a significant role in the interactions of the complexes with DNA. Moreover, the complexes bind human serum albumin more avidly than apo-transferrin.

Alterations of regulatory factors and DNA methylation pattern in thyroid cancer.

PURPOSE: DNA methylation plays an important role in thyroid oncogenesis. The aim of this study was to investigate the connection between global and local DNA methylation status and to establish the levels of important DNA methylation regulators (TET family and DNMT1) in thyroid tumours: follicular adenoma-FA, papillary thyroid carcinoma-PTC (classic papillary thyroid carcinoma-cPTC and papillary thyroid carcinoma follicular variant fvPTC). METHODS: Global DNA methylation profile in thyroid tumours tissue (41 paired samples) was assessed by 5-methylcytosine and 5-hydroxymethylcytosine levels evaluation (ELISA), along with TETs and DNMT1 genes expression quantification. Also, it was investigated for the first time TET1 and TET2 promoter's methylation in thyroid tumours. BRAF V600E mutation and RET/PTC translocation testing were performed on all investigated samples. In vitro studies upon DNA methylation in K1 thyroid cancer cells were performed with demethylating agents (5-AzaC and vitamin C). RESULTS: TET1 and TET2 displayed a significantly reduced gene expression level in PTC, while DNMT1 gene presented a high level of expression. PTC samples presented increased levels of 5-methylcytosine and low levels of 5-hydroxymethylcytosine. 5-methylcytosine levels were associated with TET1/TET2 expression levels. TET1 gene expression was significantly lower in patients positive for BRAF mutation and with RET/PTC rearrangement. TET2 gene was found hypermethylated in thyroid carcinoma patients overall, especially in PTC-follicular variant samples (p= 0.0002), where TET2 gene expression levels were significantly reduced (p= 0.0031). Furthermore, the data indicate for all thyroid cancer patients a good sensitivity (81.08%) and specificity (86.49%) regarding the use of TET1 (p< 0.0001), and TET2 (71.79%, 64.10%, p= 0.0001) hypermethylation as biomarkers for thyroid oncogenesis. CONCLUSIONS: These results suggest that TET1/TET2 gene expression and methylation may serve as potential diagnostic tools for thyroid neoplasia. Our study showed that the methylation of TET1 increases in malignant thyroid tumours. fvPTC patients presented lower methylation levels compared to cPTC and could be a discriminatory factor between two cancer types and benign lesions. TET2 is a poorer discriminator between FA and fvPTC, but it can be useful for cPTC identification. K1-cells treated with demethylating agents showed a demethylation effect, especially upon TET2 gene. The cumulative effect of L-AA and 5-AzaC proved to have a potent combined demethylating effect on genes promoter's activation and could open new perspectives for thyroid cancer therapy.

Cisplatin effect on head and neck squamous cell carcinoma cells is modulated by ERK1/2 protein kinases.

The extracellular signal-regulated kinases (ERKs) are key transducers of the extracellular signals into intracellular responses and represent major molecular players in tumorigenesis. The aim of this study was to determine how curcumin (CRM) used as an adjuvant supports the apoptotic process induced by a single chemical agent treatment (cisplatin-CisPT) on two head and neck squamous cell carcinoma cell lines (FaDu and PE/CA-PJ49) and the involvement of ERK1/2 and/or p53 activation in this process. Data have shown that the CisPt effect is potentiated by CRM. CRM induced an increase of p53 protein phosphorylation in both cell lines. CisPt decreased p53 protein phosphorylation in FaDu cells, but increased it in PE/CA-PJ49 cells. Data showed that the constitutive expression of activated ERK1/2 protein-kinase was different in the two analyzed tumor cell lines. ERK1/2 activation status was essential for both cell processes, proliferation and apoptosis induced by CisPt and/or CRM treatment on squamous cell carcinoma cells. Our data suggest that p53 phosphorylation in the apoptotic process induced by CRM treatment might require the involvement of ERK1/2. In this regard the CisPt treatment suggested that p53 phosphorylation is ERK1/2 independent in FaDu cells having a p53 gene deletion and ERK1/2 dependent in PE/CA-PJ49 cells having a p53 gene amplification. Moreover, in both tumor cell lines our results support the involvement of p53 phosphorylation-ERK1/2 activation-dependent in the apoptosis induced by combined treatments (CisPt and CRM). The use of CRM as adjuvant could increase the efficiency of chemotherapy by modulating cellular activation processes of ERK1/2 signaling pathways. In conclusion, the particular mode of intervention by which ERK1/2 might influence cell proliferation and/or apoptosis processes depends on the type of therapeutic agent, the cells' particularities, and the activation status of the ERK1/2.

Methylation of tumour suppressor genes associated with thyroid cancer.

BACKGROUND: Thyroid carcinoma is the most common endocrine malignancy worldwide. Changes in DNA methylation can cause silencing of normally active genes, especially tumour suppressor genes (TSG) or activation of normally silent genes. OBJECTIVE: The aim of this study is to evaluate the degree of promoter methylation for a panel of markers for thyroid neoplasms and to establish their relationship with thyroid oncogenesis. METHODS: To generate a comprehensive DNA methylation signature of TSGs involved in thyroid neoplasia, we use Human TSG EpiTect Methyl II Signature PCR Array-Qiagen for 24 samples (follicular adenomas and papillary thyroid carcinomas) compared with normal thyroid tissue. We extended the evaluation for three TSGs (TP73, WIF1, PDLIM4) using qMS-PCR. Statistical analysis was performed with GraphPad Prism. RESULTS: We noted four important genes NEUROG1, ESR1, RUNX3, MLH1, which presented methylated promoter in tumour samples compared to normal. We found new characteristic of thyroid tumours: methylation of TP73, WIF1 and PDLIM4 TSGs, which can contribute to thyroid neoplasia. A significant correlation between BRAF V600E mutation and RET/PTC rearrangements with TIMP3 and CDH13, RARB methylation, respectively was observed. CONCLUSIONS: TSGs promoter hypermethylation is a hallmark of cancer and a test that uses methylation quantification method is suitable for diagnosis and prognosis of thyroid cancer.

Resveratrol modulates apoptosis in 5-fluorouracyl treated colon cancer cell lines.

Since cancer is a cellular disease, it is essential to identify the development stages and use the information in the prediction, prevention, early detection and design of drug targets. Colon cancer represents a malignancy with high incidence and mortality throughout the world, its etiology involving many genetic, immunological and biochemical factors. 5-fluorouracyl (5-FU) is one of the most effective anti-cancer agents used in the treatment of colorectal cancers, but tumor chemoresistance is a major limiting factor of its use. In order to choose the most effective chemotherapeutic doses of 5-FU, and thereby diminish the side-effects, we tried to modulate the anticancer properties of 5-FU by adding dietary natural compounds. The study focused on the role of natural compounds as resveratrol (RSV) in sensitization of LoVo human colon adenocarcinoma cell line to 5-FU action. Real-time cell analysis (RTCA) by xCELLigence System was used to continuously monitor the cytotoxic effects of drug treatments on LoVo cells. RTCA allowed us to choose the proper concentrations for further end-point assays, such as flow-cytometry techniques used for the evaluation of apoptotic events, progression through cell cycle phases or nuclear antigen expression of compound-treated LoVo cells. Data obtained showed additional effects of RSV to 5-FU treatments on the increase ofapoptotic events, and suggested alternative approaches to obtain a stronger antitumor response, and diminished side-effects when low concentrations of anti-cancer drugs are used. Modulation of the mechanisms of programmed cell death process seem to be of great importance for malignant transformation, and therefore for anti-cancer therapeutic approaches.