Related Experiment Videos
Mannose toxicity in Ehrlich ascites tumor cells
1Department of Animal Biology II (Animal Physiology), Faculty of Biological Science, Complutense University, Madrid, Spain.
Abstract:
Mannosephosphate isomerase (MPI) showed a higher activity than hexokinase (HKM) in its ability to phosphorylate mannose in the spleen, thymus, brain, liver, striated muscles, kidneys, and testes from BALB/c mice. This led to a HKM/MPI ratio of less than 1 in all the organs and tissues mentioned. In contrast, Ehrlich ascites tumor cells obtained from the peritoneum of BALB/c mice had low MPI activity (half of the HKM activity and, therefore, a ratio of 2). Mannose, which is nontoxic to nontumor cells at a concentration of 0.1 M, induced marked in vitro mortality of the tumor cells. Incubation of Ehrlich ascites tumor cells with mannose resulted in a high accumulation of mannose-6-phosphate and a marked depletion of ATP which did not appear when the cells were incubated with glucose. These facts may explain the selective mortality caused by mannose in the tumor cells studied.
Insights
Mannosephosphate isomerase (MPI) is more active than hexokinase (HKM) in normal mouse tissues, but less active in tumor cells. Mannose selectively kills tumor cells by depleting ATP.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Hexokinase (HKM) and Mannosephosphate isomerase (MPI) are key enzymes in glucose and mannose metabolism.
- Differential enzyme activity can influence cellular metabolism and viability.
- Understanding these differences is crucial for exploring novel therapeutic strategies.
Purpose of the Study:
- To compare the activity of MPI and HKM in various normal mouse tissues and Ehrlich ascites tumor cells.
- To investigate the effect of mannose on Ehrlich ascites tumor cell viability and metabolism.
- To elucidate the mechanism behind mannose-induced tumor cell death.
Main Methods:
- Enzyme activity assays were performed on tissue homogenates and isolated tumor cells.
- BALB/c mice were used for tissue and tumor cell collection.
- In vitro cell culture experiments were conducted to assess mannose toxicity and metabolic changes.
Main Results:
- MPI activity was higher than HKM activity in spleen, thymus, brain, liver, striated muscles, kidneys, and testes (HKM/MPI ratio < 1).
- Ehrlich ascites tumor cells exhibited low MPI activity relative to HKM (HKM/MPI ratio = 2).
- 0.1 M mannose selectively induced mortality in Ehrlich ascites tumor cells in vitro, leading to mannose-6-phosphate accumulation and ATP depletion.
Conclusions:
- The differential activity of MPI and HKM in normal versus tumor cells creates a metabolic vulnerability in cancer cells.
- Mannose selectively targets tumor cells due to their impaired mannose metabolism.
- Mannose-induced ATP depletion is a key mechanism responsible for the selective mortality of Ehrlich ascites tumor cells.