Colon cancer poses a complex and substantial global health challenge, necessitating innovative therapeutic approaches. Chalcones, a versatile class of compounds with diverse pharmacological properties, have emerged as promising candidates for addressing colon cancer. Their ability to modulate pivotal signaling pathways in the development and progression of colon cancer makes them invaluable as targeted therapeutics. Nevertheless, it is crucial to recognize that although chalcones exhibit promise, further pre-clinical studies are required to validate their efficacy and safety. The journey toward effective colon cancer treatment is multifaceted, involving considerations such as optimizing the sequencing of therapeutic agents, comprehending the resistance mechanisms, and exploring combination therapies incorporating chalcones. Furthermore, the integration of nanoparticle-based drug delivery systems presents a novel avenue for enhancing the effectiveness of chalcones in colon cancer treatment. This review delves into the mechanisms of action of natural chalcones and some derivatives. It highlights the challenges associated with their use in pre-clinical studies, while also underscoring the advantages of employing chalcone-based nanoparticles for the treatment of colon cancer.

Colorectal cancer (CRC) is the third most common cancer in the world, with an ongoing rising incidence. Despite secure advancements in CRC treatments, challenges such as side effects and therapy resistance remain to be addressed. Photodynamic therapy (PDT) emerges as a promising modality, clinically used in treating different diseases, including cancer. Among the main challenges with current photosensitizers (PS), hydrophobicity and low selective uptake by the tumor remain prominent. Thus, developing an optimal design for PS to improve their solubility and enhance their selective accumulation in cancer cells is crucial for enhancing the efficacy of PDT. Targeted photoactivation triggers the production of reactive oxygen species (ROS), which promote oxidative stress within cancer cells and ultimately lead to their death. Ruthenium (Ru)-based compounds, known for their selective toxicity towards cancer cells, hold potential as anticancer agents. In this study, we investigated the effect of two distinct arene-Ru assemblies, which lodge porphin PS in their inner cavity, and tested them as PDT agents on the HCT116 and HT-29 human CRC cell lines. The cellular internalization of the porphin-loaded assemblies was confirmed by fluorescence microscopy. Additionally, significant photocytotoxicity was observed in both cell lines after photoactivation of the porphin in the cage systems, inducing apoptosis through caspase activation and cell cycle progression disruptions. These findings suggest that arene-Ru assemblies lodging porphin PS are potent candidates for PDT of CRC.