Porphyrin/Chlorin Derivatives as Promising Molecules for Therapy of Colorectal Cancer.

Fatima Dandash,David Y Leger,Bertrand Liagre,Mona Diab-Assaf,Vincent Sol

doi:10.3390/molecules26237268

Fatima Dandash, David Y Leger + Show 3 more

Open Access

https://doi.org/10.3390/molecules26237268

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Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related death. The demand for new therapeutic approaches has increased attention paid toward therapies with high targeting efficiency, improved selectivity and few side effects. Porphyrins are powerful molecules with exceptional properties and multifunctional uses, and their special affinity to cancer cells makes them the ligands par excellence for anticancer drugs. Porphyrin derivatives are used as the most important photosensitizers (PSs) for photodynamic therapy (PDT), which is a promising approach for anticancer treatment. Nevertheless, the lack of solubility and selectivity of the large majority of these macrocycles led to the development of different photosensitizer complexes. In addition, targeting agents or nanoparticles were used to increase the efficiency of these macrocycles for PDT applications. On the other hand, gold tetrapyrrolic macrocycles alone showed very interesting chemotherapeutic activity without PDT. In this review, we discuss the most important porphyrin derivatives, alone or associated with other drugs, which have been found effective against CRC, as we describe their modifications and developments through substitutions and delivery systems.

Highlights

Colorectal cancer (CRC) is one of the most commonly diagnosed multistage cancers and one of the leading causes of cancer mortality worldwide [1]
It is ranked the third most common cancer affecting both men and women worldwide and its five-year survival prognosis is highly dependent on the stage of the disease [9]
Common treatments come face to face with therapy resistance, which results in the low survival rates of CRC patients

Summary

Introduction

Colorectal cancer (CRC) is one of the most commonly diagnosed multistage cancers and one of the leading causes of cancer mortality worldwide [1]. Porphyrin’s nature and features play a very important role in the efficiency of PDT treatment [28] Chemotherapy drugs are another type of drug that porphyrins are used in combination with, mainly to enhance the targeting and selectivity of the bioactive groups, obtaining the full antitumor effect of the chemotherapy. Kulbacka et al tested the effect of Photofrin® on the oxidative stress factors and the results confirmed that LoVo cells responded better and more quickly to the treatment, as oxidoreductive mitochondrial activity decreased and superoxide dismutase activity increased directly after PDT. It took 3 h for the mitochondrial activity to decrease and superoxide dismutase activity to increase. P53 as a transcriptional regulator seems to play a key role in increasing the sensitivity of CRC cells to PDT treatment and the miR–iASPP interaction could be a useful pathway to overcome treatment resistance in p53-mutant or -deleted cells

Tetraphenylporphyrin and Their Derivatives

Gold Porphyrins for the Treatment of Colorectal Cancer

Findings

Conclusions