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Published on: June 20, 2015
Digitoxin Affects Metabolism, ROS Production and Proliferation in Pancreatic Cancer Cells Differently Depending on
Heléne Lindholm1, Katarina Ejeskär1, Ferenc Szekeres1
1Biomedicine, School of Health Sciences, University of Skövde, 54145 Skövde, Sweden.
Abstract:
Digitoxin has repeatedly shown to have negative effects on cancer cell viability; however, the actual mechanism is still unknown. In this study, we investigated the effects of digitoxin (1-100 nM) in four pancreatic cancer cell lines, BxPC-3, CFPAC-1, Panc-1, and AsPC-1. The cell lines differ in their KRAS/BRAF mutational status and primary tumor or metastasis origin. We could detect differences in the basal rates of cell proliferation, glycolysis, and ROS production, giving the cell lines different phenotypes. Digitoxin treatment induced apoptosis in all four cell lines, but to different degrees. Cells derived from primary tumors (Panc-1 and BxPC-3) were highly proliferating with a high proportion of cells in the S/G2 phase, and were more sensitive to digitoxin treatment than the cell lines derived from metastases (CFPAC-1 and AsPC-1), with a high proportion of cells in G0/G1. In addition, the effects of digitoxin on the rate of glycolysis, ROS production, and proliferation were dependent on the basal metabolism and origin of the cells. The KRAS downstream signaling pathways were not altered by digitoxin treatment, thus the effects exerted by digitoxin were probably disconnected from these signaling pathways. We conclude that digitoxin is a promising treatment in highly proliferating pancreatic tumors.
Insights
Digitoxin effectively induces apoptosis in pancreatic cancer cells, particularly those from primary tumors. Its mechanism appears independent of KRAS signaling, suggesting potential for treating highly proliferative pancreatic cancers.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Digitoxin exhibits anti-cancer properties, but its precise mechanism of action remains unclear.
- Pancreatic cancer cell lines display varied phenotypes based on KRAS/BRAF mutation status and origin (primary tumor vs. metastasis).
Purpose of the Study:
- To investigate the effects of digitoxin on pancreatic cancer cell viability, proliferation, glycolysis, and reactive oxygen species (ROS) production.
- To determine if digitoxin's effects are linked to KRAS downstream signaling pathways.
Main Methods:
- Treatment of four pancreatic cancer cell lines (BxPC-3, CFPAC-1, Panc-1, AsPC-1) with varying concentrations of digitoxin (1-100 nM).
- Analysis of cell proliferation, glycolysis rates, ROS production, and apoptosis induction.
- Assessment of KRAS downstream signaling pathway alterations.
Main Results:
- Digitoxin induced apoptosis in all tested cell lines, with varying sensitivity.
- Cell lines from primary tumors (Panc-1, BxPC-3) were more sensitive to digitoxin than those from metastases (CFPAC-1, AsPC-1).
- Digitoxin's effects on metabolism and proliferation were dependent on basal cellular characteristics and origin; KRAS signaling was unaffected.
Conclusions:
- Digitoxin demonstrates promise as a therapeutic agent for highly proliferating pancreatic tumors.
- The anti-cancer effects of digitoxin are likely independent of KRAS downstream signaling pathways.
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