Abstract
Colorectal cancer stands as the most common type of gastrointestinal cancer, the third most common cancer type, and the second leading cause of cancer-related mortality worldwide. Rectal cancer alone is responsible for one third of the diagnosed cases, and a trend for an increase in the early-age (under 50 years) diagnostic of rectal cancer has been observed recently, with the age of onset dropping in prospective estimates for the USA and Europe. Known risk factors promoting colorectal cancer development include both the lack of physical exercise and unhealthy eating habits, namely a diet mainly composed of processed foods, red meat, fat from animal sources, and low on vegetable, fruit, fiber, and calcium consumption. In 2016, the International Agency for Research on Cancer (IARC) concluded that obesity was associated with an increased risk of 13 types of cancer, including colorectal cancer. Evidence also suggests that weight gain during adulthood is associated with an elevated risk of developing colorectal cancer when compared with adults whose weight remains stable. Numerous epidemiological studies reported a lower risk of suffering various types of cancers when cruciferous vegetables are consumed. Their beneficial properties are attributed to the presence of sulfurous components, called isothiocyanates. Many in vitro and in vivo studies have reported that isothiocyanates elicit relevant pharmacological effects through multiple mechanisms that include modulation of phases I and II detoxification pathway enzymes, regulation of cell-cycle arrest and control of cell growth, induction of apoptosis, antioxidant activity, anti-inflammatory activity, anti-angiogenic effects, and epigenetic regulation. For this reason, isothiocyanates have been proposed as a possible therapy for the treatment of certain cancers. Among isothiocyanates, the most studied is sulforaphane, which exhibits cytostatic and cytotoxic activities mediated by a plethora of different and partly interdependent molecular mechanisms. Recently, we condensed sulforaphane with a fluorinated hydrophobic rhodol analogue, thus obtaining compounds called NITCs (newly synthesized ITCs). NITCs have intrinsic green fluorescence and can represent a theranostic platform. Theranostics refers to the union of diagnostic and therapeutic applications into a single agent thus leading to a promising therapeutic paradigm involving diagnosis, drug delivery and monitoring of treatment response. In parallel, for diagnosis purposes, particular interest is given to the development of new reactive fluorescent probes involving a minimum perturbation of the biological system. This is essential in order to understand the structure and function of cellular processes. For example, the probe should be able to penetrate the outer lipid/phospholipid membrane at a relatively high speed while preserving integrity and performance at a cellular level, and it should feature an intracellular localization profile while preserving cell viability and proliferation as well as membrane permeability. However, the application of these probes is limited due to several properties, such as: low solubility in water and in culture media, pH range, toxicity, and cell penetration. The project is designed to evaluate whether the NITCs can represent an innovative pharmacological strategy for the treatment of colorectal cancer. Studying how NITCs could impact on key molecular pathways of cancer cells would be of great interest to understand their clinical potential. The integrated preclinical models proposed here, which reproduce the biological features of human tumors by a pathological, pharmacological, and molecular point of view, will be critical to understand the mechanisms through which NITCs exposure could affect tumor development and will give the extent of their activity in comparison to those changes that occurred in normal-weight and obese animals. Moreover, the study on cells cultured in 3D will provide valua
Project details
Unibo Team Leader: Carmela Fimognari
Unibo involved Department/s:
Dipartimento di Scienze per la Qualità della Vita
Coordinator:
ALMA MATER STUDIORUM - Università di Bologna(Italy)
Total Eu Contribution: Euro (EUR) 221.637,00
Total Unibo Contribution: Euro (EUR) 111.043,00
Project Duration in months: 24
Start Date:
16/10/2023
End Date:
28/02/2026
