ABSTRACT. Genetic and epigenetic factors affecting DNA methylation and gene expression are known to be involved in the development of colon cancer, but the full range of genetic alterations and many key genes involved in the pathogenesis of colon cancer remain to be identified. NPRL2 is a candidate tumor suppressor gene identified in the human chromosome 3p21.3 region. We evaluated the role of this gene in the pathogenesis of colorectal cancer by investigating NPRL2 mRNA expression in 55 matched normal and tumor colon tissue samples using quantitative RT-PCR analysis. There was significantly decreased NPRL2 expression in 45% of the patients. Lower NPRL2 expression was observed significantly more frequently in poorly differentiated tumor samples than in highly or moderately differentiated tumors. We conclude that expression of NPRL2 contributes to progression of colon cancer.
Background: Highly aggressive and resistant to chemotherapy, pancreatic cancers are the fourth leading cause of cancer-related deaths in the western world. The absence of effective chemotherapeutics is leading researchers to develop novel drugs or repurpose existing chemicals. Alexidine Dihydrochloride (AD), an orally bioavailable bisbiguanide compound, is an apoptosis stimulating reagent. It induces mitochondrial damage by inhibiting a mitochondrial-specific protein tyrosine phosphatase, PTPMT1. The aim of this study was to test AD as a novel compound to induce apoptosis in a human pancreatic adenocarcinoma cell lines, Panc-1, MIA PaCa-2, AsPC-1, and Psn-1. Methods: After IC50 value of the AD was determined by cytotoxicity assay, apoptosis was observed by a variety of methods including the detection of early apoptosis marker Annexin V and the proteomic profile screening by apoptosis array. Multicaspase and mitochondrial depolarization were measured and changes in cell cycle were analyzed. Results: AD is found to initiate apoptosis by activating the intrinsic pathway and inhibit cell cycle in pancreatic cancer cell lines. Conclusions: As a conclusion, considering its anti-cancer properties and bioavailability, Alexidine dihydrochloride can be considered as a potential candidate against pancreatic adenocarcinomas.
Invasive fungal infections are one of the major challenges especially for immunosuppressed patients since they are drug resistant and pathogen to patients. Therefore, developing new, efficient and nonresistant antifungal agents have been a primary focus of international research. In the current study, a novel Schiff base [hetero-dinuclear copper(II) Mn(II) complex] (SB) derivative was investigated for its anticandidal activity against Candida albicans and possible mechanisms inducing cell death. The results revealed that SB treatment induces apoptotic and necrotic pathways in C. albicans ATCC10231 strain. Intracellular reactive oxygen species production determined by 2',7'-dichlorofluorescein diacetate staining was triggered by SB and amphotericin B administrations in a dose-dependent manner. Gene expression analysis demonstrated that SB exposure resulted in regulation of critical development and stress related gene expressions. SB treatment directly upregulated expression of stress related genes, DDR48 and RIM101, while suppressed important cell signaling and antibiotic resistance acquiring related genes such as HSP90, ERG11 and EFG1. Furthermore, CaMCA1 mRNA levels were found to be significantly high in SB-treated yeast cells, indicating possible caspase-like mechanism activation. Scanning electron microscopy analysis confirmed that SB treatment led to severe cell wall integrity disruption and wrinkling. The study will encourage development of SB-based anticandidal regimens but further studies are highly warranted to understand limitations and the extended use in the routine.
Purpose: Highly aggressive and resistant to chemotherapy, pancreatic cancers are the fourth leading cause of cancer-related deaths in the western world. The absence of effective chemotherapeutics is leading researchers to develop novel drugs or repurpose existing chemicals. Alexidine dihydrochloride (AD), an orally bioavailable bis-biguanide compound, is an apoptosis stimulating reagent. It induces mitochondrial damage by inhibiting a mitochondrial-specific protein tyrosine phosphatase, PTPMT1. The aim of this study was to test AD as a novel compound to induce apoptosis in a human pancreatic adenocarcinoma cell lines, Panc-1, MIA PaCa-2, AsPC-1, and Psn-1. Methods: After IC50 value of the AD was determined by cytotoxicity assay, apoptosis was observed by a variety of methods including the detection of early apoptosis marker Annexin V and the proteomic profile screening by apoptosis array. Multicaspase and mitochondrial depolarization were measured and changes in cell cycle were analyzed. Results: AD is found to initiate apoptosis by activating the intrinsic pathway and inhibit cell cycle in pancreatic cancer cell lines. Conclusions: As a conclusion, considering its anti-cancer properties and bioavailability, Alexidine dihydrochloride can be considered as a potential candidate against pancreatic adenocarcinomas. Citation Format: Ezgi Kasikci, Esra Aydemir, Bekir Mustafa Yogurtcu, Fikrettin Sahin, Omer Faruk Bayrak. Repurposing of alexidine dihydrochloride as an apoptosis-initiator and cell cycle inhibitor in human pancreatic cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-031.
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