Amphotericin B is an antibiotic used in pharmacotherapy of life-threatening mycotic infections. Unfortunately, the applicability of this antibiotic is associated with highly toxic side effects. In order to understand molecular mechanisms underlying toxicity of amphotericin B to patients, two cell lines, human normal colon epithelial cells (CCD 841 CoTr) and human colon adenocarcinoma cells (HT-29) were cultured in the presence of the drug and imaged with the application of fluorescence lifetime imaging microscopy and Raman scattering microscopy. The results of the cell viability assays confirm high toxicity of amphotericin B towards human cells. The images recorded demonstrate effective binding of amphotericin B to biomembranes. Analysis of the images reveals the operation of a defence mechanism based upon the elimination of molecules of the drug from living cells via formation of small amphotericin B-containing lipid vesicles. The fact that exosomes formed are devoid of cholesterol, as concluded on the basis of the results of Raman analysis, suggests that sequestration of sterols from the lipid phase of biomembranes is not a sole mechanism responsible for the toxic side effects of amphotericin B. Alternatively, the results imply that molecules of the drug present directly within the hydrophobic membrane core disturb the lipid membrane structure and affect their biological functions.

The aim of this study was to investigate the anticancer and antioxidant activities of low molecular weight subfractions isolated from secondary metabolites produced by the wood degrading fungus Cerrena unicolor. Human colon cancer cells (stage I) HT-29 and human normal colon epithelial cells CCD 841 CoTr were used in the research. The present study demonstrated that the low molecular weight subfractions exhibited inhibitory activity towards human colon cancer cells HT-29 at a concentration range of 25–200 μg/mL. All 6 subfractions inhibited proliferation of cells down to 47.5–9.2% at the highest concentrations in a dose-dependent manner. The most desired activity was exhibited by subfractions S, 3, 4, and 5, as the proliferation of HT-29 cells was inhibited to the greatest extent (16.5, 47.5, 42.7, and 26.1% of the control, respectively), while the effect on CCD 841 CoTr cells was the mildest (inhibition to 54.4, 71.4, 79.4, and 53.4%, compared to the control, respectively). The microscopic observation revealed that all extracts induced programmed cell death, i.e. apoptosis (up to 44.4% (subfraction 6) towards HT-29 and less than 20% (most fractions) towards CCD 841 CoTr), with no or a significantly low level of necrosis in both cell lines at the same time.

Colorectal cancer is one the most lethal cancers worldwide. Since chemotherapy is burdened with harmful effects, agents capable of enhancing the chemotherapeutic effect are being sought. Ursolic acid (UA) and oleanolic acid (OA) were analyzed for such properties. The aim of the study was to evaluate the ability of UA and OA administered individually and in combination with each other and/or a cytostatic drug camptothecin-11 (CPT-11) to limit the viability and migration of colorectal cancer cells. The cytotoxic effect of UA, OA and CPT-11 and impact on normal and cancer cell migration rate were assessed. Furthermore, the effect on factors crucial in cancer metastasis: MMP-2 and -9, uPA/uPAR, and E-cadherin were assessed with ELISA, Western Blotting and immunofluorescence assays. Statistical analysis was performed with One-Way Anova with Dunnett's test. The studied compounds exhibited the most favorable properties, i.e. they reduced the viability and migration of cancer cells. Furthermore, the secretion, activity, and cellular level of cancer MMP-2 and -9 were decreased, as a result of uPA/uPAR down-regulation. The agents also increased the level of cellular E-cadherin. The effect of the studied agents on normal cells was milder. The compounds exhibited stronger activity when administered in combination and, combined with CPT-11, enhanced anti-tumorigenic activity of the drug. The migration-limiting activity was based on down-regulation of the uPA/uPAR-dependent MMP pathway. Moreover, UA and OA exhibited a protective effect towards normal cells.

Various phytochemical studies have revealed that jackfruit (Artocarpus heterophyllus Lam.) is rich in bioactive compounds, including carotenoids, flavonoids, volatile acids, tannins, and lectins. The aim of the study was to analyze the biological activity of water-soluble polysaccharide (WSP) isolated from jackfruit and to assess its immunomodulatory, cytotoxic, and anti-oxidative effects on human colon carcinoma cells in vitro. The neutral red (NR) uptake assay revealed no toxic influence of the polymer on the viability of tumor cells (HT29 and SW620). After 24 h and 48 h of incubation, the cellular viability was not lower than 94%. The metabolic activity of the cells (MTT) at the compound concentration of 250 µg/mL was higher than 92% in comparison to the control. WSP (250 µg/mL) exerted no significant effect on the morphology of the cells was determined by May-Grünwald-Giemsa staining. WSP changed nitric oxide (NOx) production by the tumor cells depending on the time of incubation and prior 2-h stimulation of the cells with E. coli 0111:B4 LPS. It significantly stimulated IL-1β production by the tumor cells. The IL-6 level increased but that of IL-10 decreased by a WSP concentration-dependent manner. No such effect was detected in SW620. The WSP had antioxidant properties. In conclusion, water-soluble polysaccharide isolated from A. heterophyllus exhibits significant biological activity towards many types of both normal and cancerous cells. Therefore, it may be considered as a useful agent in the protection of human health or in functional and dietary nutrition.

Colorectal cancer (CRC) is one of the most common and deadliest cancers worldwide. According to the GLOBOCAN (WHO) report in 2020, nearly 2 million patients were diagnosed globally. Despite the advances in cancer diagnosis and therapy, CRC remains a global challenge. Recently, attention has been paid to the tumor microenvironment (TME), which constitutes a significant part of the tumor and mainly includes various immune cells, fibroblasts, vascular cells, and extracellular elements, such as the extracellular matrix (ECM). Many components of the stroma initially exert an anti-tumor effect, but over time, they undergo functional transformation into elements that promote tumor growth. As a result, conditions conducive to further cancer development, invasion into local tissues, and distant metastasis arise. The microenvironment of colorectal cancer (CRC) may be an important direction in the search for therapeutic targets, but it requires further understanding. The main purpose of our review is to explain the role of the complex CRC microenvironment in the progression of this cancer and highlight the potential of targeted therapy directed at the TME. Therefore, continued research into its components and typical biomarkers is necessary to improve therapy and enhance the quality of life for patients.