Carvacrol alters soluble factors in HCT-116 and HT-29 cell lines

Background/aim: Natural products are popular insights for researchers to investigate promising anti-cancer agents since some of these substances have lesser adverse effects restricting the treatment than traditional chemotherapeutic agents. A well-known monoterpene Carvacrol, widely consumed in Mediterranean cuisine and lower risks of cancer, has efficient anticancer effects. However, the mechanism of action is yet to be discovered.Materials and methods: The investigation aims to illuminate a new perceptive in the role of this substance on colorectal cancer treatment, by the means of differences in a well-defined range of soluble factors. Carvacrol effect on both HT-29 and HCT-116 cell lines was evaluated on proliferation and the IC 50 values were calculated by the RTCA xCELLigence device. Then MAGPIX assay was performed to obtain the changes in soluble factors of the cell lines.Results: The Multiplexing assay suggests some of these factors were altered in favor of surviving and proliferation in aggressive cell line HCT-116 whereas they were altered against these characters in HT-29, were correlated with the increased IC50 concentration of HCT116 in carvacrol treatment.Conclusion: The current study indicates that differences in the levels of these soluble factors could modulate the anticancer effect related to carvacrol

Targeting the tumor metabolism by oxamate potentiates the impact of chemotherapeutics in colorectal cancer cells

Purpose: Cancer cells promote lactate formation via pyruvate rather than oxidative phosphorylation by programming their metabolism to maintain proliferation under the Warburg effect. It has shown that the altered metabolic phenotype with activation of lactate dehydrogenase-A in the cancer cell may affect survival, chemotherapy resistance, and metastasis. In this direction, studies are focusing on reprogramming cancer metabolism and increase the effectiveness of chemotherapy. In this study, the main aim was to target the Warburg phenotype via the inhibition of lactate dehydrogenase with the combination of sodium oxamate and current colorectal cancer treatment options such as 5-fluorouracil and irinotecan. Methods: The effect of chemotherapeutics on the cellular behavior was evaluated by real-time cytotoxicity and migration analysis systems, and metabolic phenotype was assessed by measuring lactate, lactate dehydrogenase expression, and reactive oxygen species levels. Results: According to the results, the viability and migration of colorectal cancer cells were significantly decreased with the combination of chemotherapeutics and sodium oxamate which decreases lactate levels. (C)onclusion: As a result, the combination of sodium oxamate with chemotherapeutics hinders the cancer cell viability and migration by changing metabolic phenotype with decreased lactate.Dokuz Eylul Universit

In vitro 3D microfluidic peritoneal metastatic colorectal cancer model for testing different oxaliplatin-based HIPEC regimens

Treatment of colorectal peritoneal metastases with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) is still evolving. Conducting a randomized trial is challenging due to the high heterogeneity in the presentation of peritoneal disease and various surgical approaches. Biological research may facilitate more rapid translation of information into clinical practice. There is an emerging need for a preclinical model to improve HIPEC treatment protocols in terms of drug doses and treatment durations. The aim of the study is to design a tool that serves as an in vitro three-dimensional (3D) microfluidic peritoneal metastatic colorectal cancer model to test the efficacy of different HIPEC treatments

ORGANOID AS A NOVEL TECHNOLOGY FOR DISEASE MODELING

The organoid technology is capable to create more real-like in vitro models in terms of structure and function of the origin of the tissue. Since the three-dimensional model is able to illustrate disease pathology, cell differentiation, and recapitulation of self-renewal, lead organoid technology as a promising disease model to fill the gap between conventional two-dimensional, and in vivo disease models. The review describes the recent development of organoid disease modeling approaches

Beta-Hydroxybutyrate Augments Oxaliplatin-Induced Cytotoxicity by Altering Energy Metabolism in Colorectal Cancer Organoids

Simple Summary One of the hallmarks of cancer is the deregulation of cellular metabolism. The study investigates the potency of the administration of beta-hydroxybutyrate (BOHB) to elevate oxaliplatin's cytotoxic effect in colorectal cancer. The study employed an in vitro organoid model to assess this dual treatment. The results exhibited that non-toxic doses (7.5 and 10mM) of BOHB with oxaliplatin treatment significantly increased the cytotoxic effect of oxaliplatin in colorectal cancer organoids by altering energy metabolism, leading to higher levels of reactive oxygen species (ROS). Opposingly, healthy colon organoids were not affected by the dual treatment as in colorectal cancer organoids. Melatonin was found to neutralize this effect by protecting cancer cells from oxidative stress. The study suggests that BOHB may improve the effectiveness of chemotherapy, particularly with drugs that have a similar mechanism of action to oxaliplatin, in treating colorectal cancer, potentially leading to better outcomes for patients.Abstract Deregulation of cellular metabolism has recently emerged as a notable cancer characteristic. This reprogramming of key metabolic pathways supports tumor growth. Targeting cancer metabolism demonstrates the potential for managing colorectal cancer. Beta-hydroxybutyrate (BOHB) acts as an acetyl-CoA source for the tricarboxylic acid (TCA) cycle, possibly redirecting energy metabolic pathways towards the TCA cycle that could enhance sensitivity to oxaliplatin, through the generation of reactive oxygen species (ROS). This study explores the potential of BOHB to enhance oxaliplatin's cytotoxic effect by altering the energy metabolism in colorectal cancer. The study employed advanced in vitro organoid technology, which successfully emulates in vivo physiology. The combination treatment efficacy of BOHB and oxaliplatin was evaluated via cell viability assay. The levels of key proteins involved in energy metabolism, apoptotic pathways, DNA damage markers, and histone acetylation were analyzed via Western Blot. ROS levels were evaluated via flow cytometer. Non-toxic doses of BOHB with oxaliplatin significantly amplified cytotoxicity in colorectal cancer organoids. Treatment with BOHB and/or melatonin resulted in significantly decreased lactate dehydrogenase A and increased mitochondrial carrier protein 2 levels, indicating inhibited aerobic glycolysis and an increased oxidative phosphorylation rate. This metabolic shift induced apoptotic cell death mediated by oxaliplatin, owing to high levels of ROS. Melatonin counteracted this effect by protecting cancer cells from high oxidative stress conditions. BOHB may enhance the efficacy of chemotherapeutics with a similar mechanism of action to oxaliplatin in colorectal cancer treatment. These innovative combinations could improve treatment outcomes for colorectal cancer patients