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Diab-Assaf, M.

Publications and source records attributed to Diab-Assaf, M..

2 recordsLinked to original sources
bioRxiv2022

Photodynamic therapy in colorectal cancer using photosensitizers functionalized by arene-ruthenium complexes

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide and one of the main causes of cancer deaths in the global population. First-line treatment usually includes surgical procedures followed by combination chemotherapy. Despite the improvements in CRC treatments, the mortality rate remains very high, leading consequently to conventional treatment resistance. Several therapies were enrolled to this content in a way to find the best solutions for this disease. Photodynamic therapy (PDT) using photosensitizers (PS) presents itself as an original innovative therapeutic strategy that strongly limits the undesirable side effects of conventional treatment. However, low physiological solubility and a lack of selectivity of PS towards tumor sites are the principal restrictions of their current clinical use. Indeed, drug delivery systems are currently a key issue in cancer therapy. To overcome the problem of solubility and stability of PS such as porphyrins and their derivatives, metallic assemblies based on arene-ruthenium (Ru) units have begun to attract considerable attention as PS delivery systems. The purpose of this study was to demonstrate firstly the interest in the vectorization of tetrapyridylporphin (TPyP-arene-Ru) and Zn-tetrapyridylporphin arene-ruthenium (Zn-TPyP-arene-Ru) metallacages to increase their solubility in biological media and then, consequently their anticancer efficacy in PDT. Secondly, to elucidate the anticancer mechanism as well as identify the cell death process mediated by these new vectorized PS. The results showed that the two PS-arene-Ru complexes have a strong photocytotoxic effect after photoactivation on human HCT116 and HT-29 colorectal cancer cell lines. TPyP-arene-Ru-PDT induced outstanding cytotoxicity when compared to the Zn-TPyP-arene-Ru analogue. The two complexes show no significant effect on proliferation in the dark. In addition, results demonstrated that these two PS-arene-Ru complexes-PDT induce an apoptotic process through the appearance of a sub-G1 peak, phosphatidylserines externalization, poly-ADP ribose polymerase (PARP) cleavage and DNA fragmentation. Thus, our data contribute to highlighting that the incorporation of porphyrins in Ru-based assemblies could be an efficient vectorized system to treat CRC by PDT.

cancer biology↗
bioRxiv2022

PAMR1 negatively impacts cell proliferation and migration of Human Colon Cancer HT29 Cell Line

Colorectal cancer (CRC) is becoming one of the most prevalent cancers worldwide. Among cancers, it ranks the third place in terms of incidence and the second in terms of mortality. Even though immunological test allows fast and easy diagnostic method, there is no specific and reliable methods for early detection of CRC. Despite different treatments, high risk of re-occurrence is associated with advanced and metastatic CRC stages. An exhaustive knowledge on specific biomarkers or molecular actors involved in CRC could help to eradicate tumors or limit cancer recurrence. In this study, we focused on PAMR1 (Peptidase Domain Containing Associated with Muscle Regeneration 1), which is already considered as a tumor suppressor in breast and cervical cancers. In silico analysis of RNASeq data showed that PAMR1 was significantly downregulated in CRC tissues compared to their adjacent normal ones, as well as in cervical cancer. Our analysis showed that this downregulation, probably due to promoter hypermethylation, such as in breast cancer tissues, appeared in the four cancer stages as early as the first stage. In consistency with in silico analyses, the expression of PAMR1 was found to be lower at the transcript and protein levels in CRC tissue samples compared to normal ones, as well as in different CRC cell lines (HCT116, HT29, and SW620) compared to normal colon cell line (CCD841CoN). To understand the role of PAMR1 in CRC cancer, recombinant purified PAMR1 or concentrated secretome from CHO overexpressing PAMR1 were used to exogenously treat CRC cell lines with a focus on HT-29 cells as well as Hela cervical cancer cell line known to be sensitive to PAMR1. Transient or stable transfections were also performed to determine the impact of PAMR1 overexpression in HT29 and/or HeLa cells. In this study, we finally showed that presence of PAMR1 could reduce both cell proliferation and cell migration with a positive correlation between these biological effects and PAMR1s quantity. This implies that PAMR1 expresses anti-proliferative and anti-migrative effects in CRC. Further studies to be done in order to confirm the tumor suppressive role of PAMR1 in CRC.

cancer biology↗