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Rani Sauriasari,1,* Andisyah Putri Sekar,1,* Nurul Aisyah,1 Rezi Riadhi Syahdi,1 Eiji Matsuura2 1Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia; 2Neutron Therapy Research Center, Collaborative Research Center for OMIC & Department of Cell Chemistry, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama University, Okayama, Japan*These authors contributed equally to this workCorrespondence: Rani Sauriasari Gedung A Rumpun Ilmu Kesehatan, Jalan Prof. Dr. Sudjono D Pusponegoro, Kampus UI, Depok, Jawa Barat 16424, IndonesiaTel +62-21-7270031Email rani@farmasi.ui.ac.idIntroduction: Abnormalities in glucose metabolism in diabetic patients may lead to an increased risk of certain cancers. Epidemiological studies and meta-analysis have shown that factors such as gender, age, obesity, and insulin resistance are related to cancer incidence. The anti-p53 antibody is a known cancer marker due to tumor-associated p53 accumulation. Many studies have aimed to unravel the link between diabetes and cancer. Here, we aimed to elucidate the impact of diabetes on malignancies by analyzing anti-p53 antibody in sera of type 2 diabetes mellitus (T2DM) patients.Materials and Methods: We conducted an observational study with a cross-sectional design. A total of 149 subjects comprised of 78 T2DM patients (32 with cancer risk and 46 subjects without cancer risk), 51 T2DM patients with cancer, and 20 healthy subjects as controls from multisites. The anti-p53 antibody was measured by enzyme-linked immunosorbent assay, while HbA1c was measured using the NGSP standardized method.Results: We observed an 8.3-fold (p< 0.05) increase of anti-p53 antibody in the sera of T2DM patients and a 24-fold increase (p< 0.001) in T2DM patients with cancer compared to healthy subjects. The anti-p53 antibodies significantly increased almost three times (p< 0.05) in T2DM patients with cancer (0.72 U/mL± 0.20) compared to T2DM patients (0.25 U/mL± 0.05). Meanwhile, this antibody was almost undetectable in healthy subjects as a control group (0.03 U/mL± 0.03). The anti-p53 antibody level was higher in T2DM with cancer risk patients. However, we did not find a significant difference for it in T2DM without cancer risk patients (0.19 U/mL± 0.03) and T2DM with cancer risk patients (0.29 U/mL± 0.08). Multivariate regression analysis showed that T2DM with cancer was the only one independent factor (beta=0.218, p=0.019) that could predict the increase of anti-p53 antibody, controlled by age, gender, BMI, DM duration, and HbA1c.Conclusion: Our results showed that anti-p53 antibody almost not detected in healthy subjects, but 8.3-fold increase in the sera of T2DM patients and 24-fold increase in T2DM patients with cancer. Therefore, this biomarker provides new information which explains the link between diabetes and cancer.Keywords: anti-p53 antibodies, P53, cancer, diabetes mellitus &nbsp

We investigated the molecular mechanisms responsible for the induction of apoptosis in mouse monocytic macrophage cell line J774A.1 stimulated by 7-ketocholesterol (7-KC). Cell apoptosis was detected by Annexin V-propidium iodide (PI) staining. The DNA-binding activity of nuclear factor kappa B (NF-kappaB) was assessed by electrophoretic mobility shift assay (EMSA). Results showed that 7-KC-stimulation in J774A.1 cells activated NF-kappaB, which is involved in cell apoptosis, in a time- and dose-dependent manners. 7-KC was also found to increase the binding activity of NF-kappaB to specific DNA binding sites, a possible mechanism for the induction of the cell apoptosis. Moreover, these effects were partially inhibited by pyrrolidine dithiocarbamate (PDTC), an NF-kappaB inhibitor. Taken together, 7-KC may be an important factor in atherosclerosis due to the ability of 7-KC to induce cell apoptosis, which is at least partially mediated through the activation of NF-kappaB.