Single nucleotide polymorphisms of DNA repair genes alter protein function and modulate DNA repair efficiency in various cancers. The X-ray repair cross-complementing group (XRCC) is responsible for the repair of DNA base damage and single-strand breaks. The aim of our study was to investigate the association of XRCC1 Arg399Gln and XRCC3 Thr241Met polymorphisms with the susceptibility to develop oral squamous cell carcinoma (OSCC) in Turkish subjects. One hundred eleven patients with OSCC and 148 healthy controls were recruited for the study. Genetic analysis was performed using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). We found that the XRCC1 Arg399Gln Gln/Gln genotype and Gln allele were risk factors for OSCC. Also, Arg/Arg genotype and Arg allele had protective effects against OSCC. Relative to XRCC3 Thr241Met polymorphism, carrying homozygote variants (Thr/Thr and Met/Met) was related with elevated OSCC risk. However, the heterozygote genotype and Thr allele variants were shown to be protective against OSCC. We suggest that XRCC1 Arg399Gln Gln/Gln genotype, Gln allele, and homozygote variants of XRCC3 Thr241Met polymorphism may be a risk factor for predisposition of OSCC in Turkish. In addition, XRCC3 Thr241Met genotype could be associated with tumor size and level of daily smoking.
Objective: Renal cancers are highly resistant to standard hormonal therapy, radiotherapy, and chemotherapy, and the survival rates are extremely low. Betulinic acid is a pentasilic triterpenoid saponin of lupine type obtained from various natural plants, especially from the shell of Betula plant. Betulinic acid was shown both in in vivo, and in vitro to have the ability to induce apoptotic pathways causing no toxicity for normal cells, and also has immunomodulatory effects. The aim of the present project is to investigate the anticancer effects of betulinic acid on CAKI-2 (ATCC® HTB-47™; clear cell renal carcinoma), ACHN (ATCC® CRL-1611™; renal cell adenocarcinoma) and MRC-5 (ATCC® CCL-171™: normal lung fibroblast) cell lines. Materials and Methods: The dose, and time-dependent cell viability was determined using the WST-1 test first in cell lines, and then apoptotic activity was determined with Annexin-V, apoptosis related nucleosomal enrichment factor levels, and Caspase 3 / BCA activity. Results: Betulinic acid reduced the CAKI-2, and ACHN cell viability in dose, and time-dependent manner inducing the apoptotic pathway. Conclusion: Researchers in the present study concluded in accordance with the results of Annexin-V, apoptosis-associated nucleosomal enrichment factor levels and Caspase 3 / BCA activity that betulinic acid triggered the apoptosis in both renal cancer cell lines, especially by the Caspase 3 activity.
Renal cancer is the most lethal urological cancer and characterized by high metastasis rate at initial diagnosis and drug resistance to current chemotherapeutics. Betulinic acid is a pentacyclic triterpene with broad biological activity that occurs naturally in variety of plants. Even though the anti-cancer e cacy of betulinic acid have been reported by many studies, the information about the pathways and the molecules which are affected by betulinic acid in renal cancer are limited. Epithelial-mesenchymal transition (EMT) is considered as the initial step of metastasis and contributes to drug resistance of cancer cells. Depending on the role of EMT in cancer progression and drug resistance, targeting EMT may represent an effective strategy in this context. Therefore, we aimed to investigate the anti-metastatic effects of betulinic acid on renal cell carcinoma cells by evaluating two EMT markers, SNAIL-1, and SDC-2. Following the treatment of betulinic acid at determined doses by WST-1 cytotoxicity assay in our previous study, SDC-2 expression level was decreased in both cell lines. Additionally, in correlation with this result, we also found a reduction in SDC-2 and SNAIL-1 protein levels which are measured by ELISA. Furthermore, the migration and invasion capacities were suppressed by betulinic acid treatment in metastatic renal adenocarcinoma ACHN cells. Taken together, our ndings indicate that betulinic acid may constitute a potential treatment approach for renal cancer with further investigations.
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