Metadichol-Induced Differentiation of Pancreatic Ductal Cells (PANC-1) into Insulin-Producing Cells

Abstract

Endocrine gene expression in PANC-1, a type of pancreatic cancer cell, has been studied in the context of their potential to be reprogrammed toward a normal, differentiated state. Alkaline phosphatase activity has also been shown in pluripotent stem cells to differentiate between feeder and parental cells in reprogramming experiments. Metadichol®-based cell program­ming holds promise as a versatile and potentially safer approach for manipulating cellular behavior without the use of viral vectors, gating, or CRISPR. Using qRT‒PCR the results show multifold increase in the gene expression of CA9, GCG, INS MAFA, NEUROD1, NGN3, NKX2-2, PAX6: PDX1, SLC2A2, FOXO1, and SIRT1. ALP levels increased and this activity is often used to distinguish stem cells from feeder cells as well as from parental cells in reprogramming experiments. Pluripotency was confirmed by the presence of islet-like structures on day eight. Metadichol exhibits anticancer activity with a CC50 value of 5.50 µg/ml compared to standard doxorubicin with a CC50 value of 10.28 µg/ml. At 100 ug/ml Metadichol is 82% cytotoxic.in a MTT assay Anti-tumor gene Klotho’s expression was increased 70fold on day eight. All the genes seen expressed regulate endocrine cell development in the pancreas and are involved in insulin and glucagon secretion. Gene network analysis is presented to show how Metadichol induced expression leads to a closed loop feedback network and biological process that would help in mitigating diabetes and other related disorders.