Spastic Paraplegia 20 and Serine/Threonine Protein Kinase 31 Expression for the Detection of Colorectal Cancer.

BACKGROUND/AIMS: Genetic alterations, including changes in the expression of spastic paraplegia 20 (SPG20) and serine/threonine protein kinase 31 (STK31), may play an important role in the carcinogenesis of colorectal cancer (CRC). Identification of such changes is suitable for the recognition of tumors at an early stage, which would significantly improve patient survival. While recent studies have identified that SPG20 and STK31 expression levels increase in CRC tissues, their use as a biomarker is yet to be investigated. Our aim was to determine whether circulating SPG20 and STK31 mRNAlevels could help distinguish between patients with CRC and healthy individuals. Additionally, we aimed to analyze the correlation between SPG20 and STK31 expression patterns and the tumor stage in patients with CRC. METHODS: Venous blood samples from 50 patients with CRC and 50 healthy controls were used. RNA extraction was performed, and the mRNA expression of SPG20 and STK31 was determined using RT-qPCR. RESULTS: STK31 and SPG20 mRNA levels were significantly upregulated in patients compared to those in controls. There was a strong positive correlation between the expression of the two potential tumor biomarkers, STK31 and SPG20 (R=0.636, p=0.000). However, there was no significant relationship between the expression of STK31 or SPG20 and patient data, including demographic, clinical, pathological, and laboratory data. Additionally, there was a significant correlation between the expression level of STK31, but not SPG20, and patient disease-free survival (DFS) and overall survival (OS). CONCLUSION: Circulating mRNA levels of SPG20 and STK31 could be used as ideal noninvasive biomarkers for early diagnosis of CRC. They could assist the oncologist in recommending appropriate management strategies for individual patients.

Curcumin analogue 1,5-bis(4-hydroxy-3-((4-methylpiperazin-1-yl)methyl)phenyl)penta-1,4-dien-3-one mediates growth arrest and apoptosis by targeting the PI3K/AKT/mTOR and PKC-theta signaling pathways in human breast carcinoma cells.

Recent developments in the literature have demonstrated that curcumin exhibit antioxidant properties supporting its anti-inflammatory, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Despite the valuable findings of curcumin against different cancer cells, the clinical use of curcumin in cancer treatment is limited due to its extremely low aqueous solubility and instability, which lead to poor in vivo bioavailability and limited therapeutic effects. We therefore focused in the present study to evaluate the anti-tumor potential of curcumin analogues on the human breast carcinoma cell lines MDA-MB-231 and MCF-7, as well as their effects on non-tumorigenic normal breast epithelial cells (MCF-10). The IC50 values of curcumin analogue J1 in these cancer cell lines were determined to be 5 ng/ml and 10 ng/ml, in MDA-MB-231 and MCF-7 cells respectively. Interestingly, at these concentrations, the J1 did not affect the viability of non-tumorigenic normal breast epithelial cells MCF-10. Furthermore, we found that J1 strongly induced growth arrest of these cancer cells by modulating the mitochondrial membrane potentials without significant effect on normal MCF-10 cells using JC-1 staining and flow cytometry analysis. Using annexin-V/PI double staining assay followed by flow cytometry analysis, we found that J1 robustly enhanced the induction of apoptosis by increasing the activity of caspases in MDA-MB-231 and MCF-7 cancer cells. In addition, treatment of breast cancer cells with J1 revealed that, in contrast to the expression of cyclin B1, this curcumin analogue vigorously decreased the expression of cyclin A, CDK2 and cyclin E and subsequently sensitized tumor cells to cell cycle arrest. Most importantly, the phosphorylation of AKT, mTOR and PKC-theta in J1-treated cancer cells was markedly decreased and hence affecting the survival of these cancer cells. Most interestingly, J1-treated cancer cells exhibited a significant inhibition in the activation of RhoA followed by reduction in actin polymerization and cytoskeletal rearrangement in response to CXCL12. Our data reveal the therapeutic potential of the curcumin analogue J1 and the underlying mechanisms to fight breast cancer cells.