Changes in NAD/ADP-ribose metabolism in rectal cancer

Abstract

The extent of ADP-ribosylation in rectal cancer was compared to that of the corresponding normal rectal tissue. Twenty rectal tissue fragments were collected during surgery from patients diagnosed as having rectal cancer on the basis of pathology results. The levels of ADP-ribosylation in rectum cancer tissue samples (95.9 ± 22.1 nmol/ ml) was significantly higher than in normal tissues (11.4 ± 4 nmol/ml). The level of NAD + glycohydrolase and ADP-ribosyl cyclase activities in rectal cancer and normal tissue samples were measured. Cancer tissues had significantly higher NAD + glycohydrolase and ADPribosyl cyclase activities than the control tissues (43.3 ± 9.1 vs 29.2 ± 5.2 and 6.2 ± 1.6 vs 1.6 ± 0.4 nmol mg -1 min -1 ). Approximately 75% of the NAD + concentration was consumed as substrate in rectal cancer, with changes in NAD + /ADP-ribose metabolism being observed. When [ 14 C]-ADP-ribosylated tissue samples were subjected to SDS-PAGE, autoradiographic analysis revealed that several proteins were ADPribosylated in rectum tissue. Notably, the radiolabeling of a 113-kDa protein was remarkably greater than that in control tissues. Poly(ADP)-ribosylation of the 113-kDa protein in rectum cancer tissues might be enhanced with its proliferative activity, and poly(ADP)-ribosylation of the same protein in rectum cancer patients might be an indicator of tumor diagnosis.

PARP1 expression in mantle cell lymphoma: the utility of PARP1 immunohistochemistry and its relationship with markers of DNA damage

“…PARP1 inhibitors have emerged as promising adjuvant agents to enhance chemotherapeutic effects in various cancers . Increased expression of PARP1 at the level of mRNA, protein and enzyme activity has been reported in a number of cancers, including ovarian, hepatocellular, colorectal and leukemias . Olaparib (a PARP1 inhibitor) has shown encouraging results in MCL‐related pre‐clinical studies .…”

The Small Molecule GMX1778 Is a Potent Inhibitor of NAD+ Biosynthesis: Strategy for Enhanced Therapy in Nicotinic Acid Phosphoribosyltransferase 1-Deficient Tumors

“…First, tumor cells exhibit a high rate of NAD ϩ turnover due to the high levels of ADP-ribosylation activity required for DNA repair, genome stability, and telomere maintenance (10,37,39). For example, the base excision-repair pathway is dependent on poly(ADP-ribose) polymerase 1 for efficient DNA repair and poly(ADP-ribose) polymerase 1 is known to be one of the major cellular NAD ϩ - FIG.…”

“…Cancer cells exhibit a significant dependence on NAD ϩ for support of the high levels of ATP production necessary for rapid cell proliferation. They also consume large amounts of this cofactor via reactions that utilize poly(ADP) ribosylation, including DNA repair pathways (10,37,39).…”

microRNAs Biogenesis, Functions and Role in Tumor Angiogenesis

“…A PARP13 anticancer role was also found in Hepatitis B Virus related-liver cancer and leukemia, thanks to its antiviral activity (116,117). PARP1 expression was found to increase in breast, uterine, lung cancer, ovarian cancer, skin cancer, and non-Hodgkin's lymphoma (118)(119)(120). In breast cancers, including triplenegative breast cancers, PARP1 expression negatively correlates to the estrogen receptor, progesterone receptor, or epidermal growth factor receptor-2 expression (121).…”