Click linker: efficient and high yielding synthesis of a new family of kojic acid congeners as cytotoxic agents.

Highly efficient methodology was developed for the construction of functionalized Kojic acid involving Click linker via 1,3-dipolar cycloaddition and their cytotoxicity against MCF-7, MIAPaCa-2 and DU145 mammalian cell lines were evaluated. Preliminary studies on structure-activity-relationship (SAR) revealed that substitution at C-2 of kojic acid as well as C-5 of 1,2,3-triazole motif played a major role in the activity profile. Kojic acid 1,2,3-triazole analogue 3 b containing an alkyl chain (n = 6) exhibited two fold potent activity than the parent compound, kojic acid against MCF-7 and MIA PaCa-2 cell lines. It induced apoptosis in these cell lines via ID1/PARP1 mediated pathway. The structures of the new analogues of kojic acid 1,2,3-triazole were confirmed by the detailed spectroscopic data analysis.

Inhibitor of DNA binding/differentiation proteins as IDs for pancreatic cancer: Role in pancreatic cancer initiation, development and prognosis.

A family of inhibitors of cell differentiation or DNA-binding proteins, known as ID proteins (ID1-4), function as mighty transcription factors in various cellular processes, such as inhibiting differentiation, promoting cell-cycle progression, senescence, angiogenesis, tumorigenesis, and metastasis in cancer. Pancreatic cancer represents the deadliest cancer with the lowest survival rate of 10% due to the diagnosis at an advanced fatal stage and therapeutic resistance. Modestly, the only curative option for this lethal cancer is surgery but is done in less than 15-20% of patients because of the locally aggressive and early metastatic nature. Finding the earliest biomarkers and targeting the various hallmarks of pancreatic cancer can improve the treatment and survival of pancreatic cancer patients. Therefore, herein in this review, we explore in depth the potential roles of ID proteins function in hallmarks of pancreatic cancer, signaling pathways, and its oncogenic and tumor-suppressive effects. Hence, understanding the roles of dysregulated ID proteins would provide new insights into its function in pancreatic cancer tumorigenesis.

Western blotting: a powerful staple in scientific and biomedical research.

Western blotting (WB), also known as immunoblotting, is a well-known molecular biology method that biologists often use to investigate many features of the protein, ranging from basic protein analysis to disease detection. WB is simple, unique, rapid, widely used routine tool with easy interpretation and definite results. It is being used in various fields of science, research and development, diagnostic labs and hospitals. The principle of WB is to accomplish the separation of proteins based on molecular weight and charge. This review addresses in detail the individual steps involved in the WB technique, its troubleshooting, internal loading controls, total protein staining and its diverse applications in scientific research and clinical settings, along with its future perspectives.

Autophagic and apoptotic cell death induced by the quinoline derivative 2-(6-methoxynaphthalen-2-yl)quinolin-4-amine in pancreatic cancer cells is via ER stress and inhibition of Akt/mTOR signaling pathway.

Pancreatic cancer (PC) is among the most lethal cancers and is resistant to existing therapies, which highlights the need for new and alternative therapeutic treatments. Autophagy is emerging as one of the alternative cell death mechanisms and is well known to cross-talk with apoptosis. Autophagy can act as a viable option to treat highly resistant PC. The current study investigates and provides insight into the autophagic and apoptotic cell death induced by quinoline derivative 2-(6-methoxynaphthalen-2-yl)quinolin-4-amine (6MN-4-AQ) in PC cell lines PANC-1 and MIA PaCa-2. Treatment with 6MN-4-AQ reduced cell viability in concentration dependent manner (2-16 µM) and inhibited the clonogenic potential of PC cells at a concentration of 4 µM for 24 h. Further, we found that 6MN-4-AQ induced both apoptosis and autophagic cell death simultaneously. We identified that 6MN-4-AQ induced autophagic cell death by forming cytoplasmic vacuoles, the elevation of autophagy flux, increase in LC3-II, Beclin-1 protein expression, and degradation of p62. Moreover, 6MN-4-AQ induced apoptosis via Caspase-3 activation and cleavage of PARP in PC cells. Upon investigating the underlying mechanism associated with 6MN-4-AQ induced cell death, it was observed that 6MN-4-AQ treatment is able to suppress the Akt/mTOR pathway and induced ER stress leading to the induction of autophagy. Also, 6MN-4-AQ treatment suppressed epithelial to mesenchymal transition by reducing the protein expression of SLUG, snail, and vimentin. Subsequently, 6MN-4-AQ inhibited cell migration and invasion by down regulating MMP-7 and MMP-9 protein expression, suggesting that 6MN-4-AQ may serve as a plausible therapeutic agent for PC.