Background/Aim: The occurrence of BRAF V600E mutation causes an up-regulation of the B-raf kinase activity leading to the stabilization of hypoxia-inducible factor 1-alpha (HIF-1α) -the promoter of the 6-phosphofructo-2kinase/fructose-2,6-biphosphatase 3 (PFKFB3) enzyme. The aim of the study was to examine the effect of the (2E)-3-(3-Pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO), as an inhibitor of PFKFB3, on human melanoma cells (A375) with endogenous BRAF V600E mutation. Materials and Methods: A375 cells were exposed to different concentrations of 3PO and the following tests were performed: docking, cytotoxicity assay, immunocytochemistry staining glucose uptake, clonogenic assay, holotomography imaging, and flow cytometry. Results: Our studies revealed that 3PO presents a dose-dependent and time-independent cytotoxic effect and promotes apoptosis of A375 cells. Furthermore, the obtained data indicate that 3PO induces cell cycle arrest in G1/0 and glucose uptake reduction. Conclusion: Taking all together, our research demonstrated a here should be proapoptotic and antiproliferative effect of 3PO on A375 human melanoma cells.Malignant melanoma is a neoplasm derived from melanocytes (pigment-containing cells) localized typically in the skin as well as in the eye, intestines, inner ear and meninges (1). Its cutaneous form is considered as the most aggressive and the deadliest type of skin cancer. The primary locus of tumor exhibits a predilection for early metastasis, which can occur even from thin carcinomas. Therefore, the early diagnosis of melanoma is essential for the further success of the applied treatment (1).Depending on the tumor's features, possible therapeutic methods may include surgery, chemotherapy, radiotherapy, immunotherapy or molecularly targeted therapies (2). Surgical excision of melanoma at the earliest possible stage is essential for a successful therapeutic outcome. Radiotherapy may be recommended for the treatment of skin, bone and brain metastases (3). Chemotherapy with dacarbazine, and temozolomide was the first systemic treatment applied in advanced melanoma; however, overall survival rates (OS) did not show significant improvement (4). In a phase III study comparing dacarbazine and temozolomide the response rate was 12% and 13%, respectively (5). None of these two alkylating agents affect a specific molecular pathway, thus they cannot be used in personalized oncology. Despite novel reports on new therapy achievements in the field of immunotherapy or biological treatment, these methods are insufficient and burdened with certain disadvantages and side-effects (6). This causes an urgent need for finding new treatment options for melanoma.BRAF (v-raf murine sarcoma viral oncogene homolog B) gene is located at chromosome 7 (7q34) and encodes B-raf 2613

Cancers are one of the leading causes of deaths affecting millions of people around the world, therefore they are currently a major public health problem. The treatment of cancer is based on surgical resection, radiotherapy, chemotherapy or immunotherapy, much of which is often insufficient and cause serious, burdensome and undesirable side effects. For many years, assorted secondary metabolites derived from plants have been used as antitumor agents. Recently, researchers have discovered a large number of new natural substances which can effectively interfere with cancer cells’ metabolism. The most famous groups of these compounds are topoisomerase and mitotic inhibitors. The aim of the latest research is to characterize natural compounds found in many common foods, especially by means of their abilities to regulate cell cycle, growth and differentiation, as well as epigenetic modulation. In this paper, we focus on a review of recent discoveries regarding nature-derived anticancer agents.

The current age of dynamic development of the space industry brings the mankind closer to routine manned space flights and space tourism. This progress leads to a demand for intensive astrobiological research aimed at improving strategies of the pharmacological protection of the human cells against extreme conditions. Although routine research in space remains out of our reach, it is worth noticing that the unique severe environment of the Earth’s stratosphere has been found to mimic subcosmic conditions, giving rise to the opportunity to use the stratospheric surface as a research model for the astrobiological studies. Our study included launching into the stratosphere a balloon containing mammalian normal and cancer cells treated with various compounds to examine whether these substances are capable of protecting the cells against stress caused by rapidly varying temperature, pressure, and radiation, especially UV. Owing to oxidative stress caused by irradiation and temperature shock, we used natural compounds which display antioxidant properties, namely, catechin isolated from green tea, honokiol derived from magnolia, curcumin from turmeric, and cinnamon extract. “After-flight” laboratory tests have shown the most active antioxidants as potential agents which can minimize harmful impact of extreme conditions on human cells.

1.AbstractCurrently ongoing age of the dynamic development of the space industry brings the mankind closer to the routine manned space flights and space tourism. That progress leads to a demand for intensive astrobiological research aimed at improving strategies of the pharmacological protection of the human cells against extreme conditions. Although routine research in space remain out of our reach, it is worth noticing that unique severe environment of the Earth’s stratosphere have been found to mimic subcosmic conditions, giving rise to the opportunity for use of stratospheric surface as a research model for the astrobiological studies. Our study included launching balloon into the stratosphere containing the human normal and cancer cells treated with various compounds to examine whether these medicines are capable to protect the cells against the stress caused by rapidly varying temperature, pressure and radiation, especially UV. Due to oxidative stress caused by irradiation and temperature shock, we used natural compounds which display antioxidant properties, namely catechin isolated from green tea, honokiol derived from magnolia, curcumin from turmeric and cinnamon extract. “After-flight” laboratory tests displayed the most active antioxidants as potential agents which can minimize harmful impact of extreme conditions to the human cells.

Nowadays new medicines are being sought to effectively fight against melanoma. Metabolites of natural compounds have been used for antimelanoma therapy for a long time, but in recent years, new active substances of natural origin have been discovered with proven effects that interfere with the metabolism of tumor cells. The most interesting are compounds exhibiting low toxicity against normal cells, and selective cytotoxicity against cancer cells. One of these compounds is curcumin—a component of turmeric. Curcumin has immunomodulatory, anti-inflammatory, anticancer effects, affects the phase II enzymes and is a potent photosensitizer, thus showing strong potential for use in oncotherapy. Curcumin has been investigated as a potential photosensitizer (PS) in anticancer photodynamic therapy (PDT). The phototoxic effect of curcumin is dependent on proper formulations of the compound because of the lipophilic nature of the molecule and the extremely low water solubility at physiologic conditions. In the present study, the combination of curcumin was investigated in PDT using human melanoma amelanotic cell line (C32) and normal human fibroblasts from primary culture as control cells. The cells were maintained in culture and then treated with curcumin at concentrations of 5-50 μM for 2, 24 and 48. Then cells were irradiated with blue light (20 J/cm2) for 5 minutes and incubated for 24 hours. The efficacy of photodynamic effect was evaluated by viability assay (MTT). Additionally, cell death assay and cellular reactive oxygen species (ROS) assay were assessed. The intracellular distribution of curcumin after different time of incubation was visualized by CLSM method. The results suggest that curcumin may be a potent alternative to commonly used cytostatics. Depending on the curcumin concentration, the cell survival ranged from 18.95% of control cells after incubation with 50 μM curcumin to 0.91% after PDT. It has been shown that PDT with curcumin can increase oxidative stress and number of apoptotic and necrotic cells in comparison to incubation with curcumin without irradiation. The reduced and selective anticancer activity as compared to other drugs can be the basis for the use of curcumin also in complementary treatment of amelanotic melanoma. This study has revealed for the first time that PDT with curcumin appears to represent an efficient alternative for the treatment of amelanotic melanoma through the in situ application of the photosensitizer followed by irradiation of the photosensitizer-loaded area. Thus, the proposed protocol seems to be promising in the amelanotic melanoma, which is extremely resistant to standard chemo- and radiotherapy. Citation Format: Stanislaw Kwiatkowski, Dawid Przystupski, Krzysztof Kotowski, Agata Gorska, Weronika Bartosik, Aleksander Kielbik, Jolanta Saczko, Julita Kulbacka. The effect of irradiation with curcumin as a possible form of amelanotic melanoma treatment [abstract]. In: Proceedings of the AACR Special Conference on Melanoma: From Biology to Target; 2019 Jan 15-18; Houston, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(19 Suppl):Abstract nr A08.