Exploring the possible implication of curcumin in the treatment of colorectal cancer

Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide, being the third most common cancer in men and the second most commonly occurring cancer in women worldwide.1 Turmeric (Curcuma longa Linn.) has been part of Chinese medicine for 4,000 years.2 Curcuminoids, especially the main phytochemical curcumin, are currently attracting attention for their bioactive properties, particularly for their efficacy as potential anticancer agents in various cancer cell line models. Thus, the aim of this work was to review the literature in order to evaluate the potential antitumoral activity of curcumin in CRC. Agarwal and his team described the potential antitumoral role curcumin could play, unveiling curcumin-induced reactive oxygen species (ROS) generation effects on Smad4 and p53 mutated colon adenocarcinoma HT29 cells, treated with or without N-acylcysteine (NAC). The data, thus, demonstrating dose- and time-dependent cell cycle arrest at S and G2/M phase, and induced apoptosis via alteration of the mitochondrial membrane as the potential antitumoral mechanisms of intracellular curcumin-induced ROS. Significant attention will also be given to the role of curcumin in enhancing established pharmacological therapies against CRC. Combination of curcumin with therapeutic cancer agents like 5-fluorouracil and doxorubicin (Dox) has already showed both in vivo and in vitro improved cytotoxic and chemotherapeutic effects against gut-related carcinomas.3 Hereby, it will be described Sesarman et al. work’s analysis on the potential outcomes of co-encapsulating curcumin and Dox in long-circulating liposomes (LCL), which resulted to favor the antitumoral suppressive effects of the chemotherapeutic, while at the same time limiting the cytotoxicity of it, and the antineoplastic phenotype of cells in the tumor micro-environment (TME) of C26 murine colon carcinoma model cells. Interestingly, as our understanding of CRC grows, it is becoming increasingly evident that stem cells play a substantial role in carcinogenic development and progression, therefore, showing curcumin efficacy in inhibiting the neoplastic features of cancer stem cells would further proof its biological potentials. Thus, Kim’s team of researchers’ work on Lgr5+ stem cells was taken into consideration for the matter, where the potential chemopreventive effects of using a combination of pleiotropic dietary compounds, in particular n-3 polyunsaturated fatty acids (n-3 PUFAs) and curcumin, was analyzed. The resulted outcomes depicted the targeted apoptosis promotion, damage-repairing methylguanine-methyl transferase (MGMT) expression and p53 signaling induction, and a fast incorporation into the target’s site as the potential chemoprotective effects the co-administration of the compounds could exert. Although the potential antitumor effect of curcumin is not comparable to that of commonly used chemotherapeutics, the co-formulation of it alongside antineoplastic drugs could lay the basis for a possible reduction of the dosage the pharmacological compounds need. This could possibly lead to a potential reduction of adverse effects during treatment and diminishing, concurrently, the economic burden that the therapy has on the healthcare system. Thus, further studies and clinical trials comprehending the exact underlying mechanisms and effects curcumin exerts on CRC and the impact the phytometabolite has on consequent metastases are needed and crucial.