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Updated: Jan 24, 2026
Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
Published on: March 14, 2014
PKM2 Knockdown Induces Autophagic Cell Death via AKT/mTOR Pathway in Human Prostate Cancer Cells
Prasanta Dey1, Amit Kundu1, Richa Sachan1
1School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea.
Background/Aims:
Pyruvate kinase M2 (PKM2) is essential for aerobic glycolysis. Although high PKM2 expression is observed in various cancer tissues, its functional role in cancer metabolism is unclear. Here, we investigated the role of PKM2 in regulating autophagy and its associated pathways in prostate cancer cells.
Methods:
Immunohistochemistry was performed to compare the expression level of PKM2 in prostate cancer patients and normal human, whereas expression of PKM2 in several cell lines was also examined by using western blot. PKM2 expression was silenced using various small interfering RNAs (siRNAs). Cell viability was examined using IncuCyte ZOOM™ live cell imaging system. Western blotting and immunofluorescence were performed to investigate the PKM2 knockdown on other cellular signaling molecules. Acridine orange and Monodansylcadaverine staining was performed to check effect of PKM2 knockdown on autophagy induction. High performance thin layer chromatography was carried out to quantify the level of different cellular metabolites (pyruvate and lactate). Colony formation assay was performed to determine the ability of a cells to form large colonies.
Results:
PKM2 was highly expressed in prostate cancer patients as compared to normal human. PKM2 siRNA-transfected prostate cancer cells showed significantly reduced viability. Acridine orange, Monodansylcadaverine staining and western blotting analysis showed that PKM2 downregulation markedly increased autophagic cell death. Results of western blotting analysis showed that PKM2 knockdown affected protein kinase B/mechanistic target of rapamycin 1 pathway, which consequently downregulated the expression of glycolytic enzymes lactate dehydrogenase A and glucose transporter 1. Knockdown of PKM2 also reduced the colony formation ability of human prostate cancer cell DU145.
Conclusion:
To the best of our knowledge, this is the first study to show that PKM2 inhibition alters prostate cancer cell metabolism and induces autophagy, thus providing new perspectives for developing PKM2-targeting anticancer therapies for treating prostate cancer.
Insights
Inhibition of pyruvate kinase M2 (PKM2) in prostate cancer cells significantly reduces viability and induces autophagic cell death. This highlights PKM2 as a potential therapeutic target for prostate cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Metabolism
Background:
- Pyruvate kinase M2 (PKM2) is crucial for aerobic glycolysis and is highly expressed in various cancers.
- The precise role of PKM2 in cancer metabolism and its regulation of cellular processes like autophagy remain unclear.
Purpose of the Study:
- To investigate the role of PKM2 in regulating autophagy and associated pathways in prostate cancer cells.
- To explore the potential of PKM2 as a therapeutic target in prostate cancer.
Main Methods:
- Compared PKM2 expression in prostate cancer tissues and cell lines using immunohistochemistry and western blot.
- Silenced PKM2 expression using siRNAs and assessed effects on cell viability, autophagy, and key signaling pathways.
- Quantified metabolic changes and colony formation ability following PKM2 knockdown.
Main Results:
- PKM2 was significantly upregulated in prostate cancer tissues and cell lines.
- PKM2 knockdown reduced prostate cancer cell viability and colony formation.
- Downregulation of PKM2 induced autophagic cell death and affected the Akt/mTOR pathway, decreasing expression of glycolytic enzymes and glucose transporter 1.
Conclusions:
- PKM2 inhibition alters prostate cancer cell metabolism and induces autophagy.
- This study provides novel insights into PKM2's role in prostate cancer, suggesting it as a promising target for anticancer therapies.
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