Hydrogen peroxide and cisplatin regulate the ROS/PKM2 pathway to affect the growth of cancer

Li-Yuan Bai1,2, Chang-Fang Chiu1,3, Chia-Yung Wu1

  • 1Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital Taichung 404, Taiwan.

PubMed

Insights

Reactive oxygen species (ROS) induce cancer cell death. Pyruvate kinase M2 (PKM2) nuclear levels decrease with ROS-inducing treatments, suggesting PKM2 as a potential anticancer target.

Area of Science:

  • Oncology
  • Biochemistry
  • Cell Biology

Background:

  • Aberrant reactive oxygen species (ROS) production contributes to DNA damage, chronic diseases, and cancer.
  • Pyruvate kinase M2 (PKM2), an enzyme crucial for glycolysis and energy metabolism, is overexpressed in various malignancies.

Purpose of the Study:

  • To investigate the impact of ROS-inducing agents on cancer cells and the role of PKM2.
  • To explore the potential of targeting PKM2 in anticancer therapy.

Main Methods:

  • Induction of ROS using hydrogen peroxide (H2O2) and cisplatin in pancreatic, oral, gastric, and hepatocellular carcinoma cells.
  • Assessment of apoptosis and nuclear p-PKM2 levels.
  • Evaluation of antioxidant effects using N-acetylcysteine (NAC).

Main Results:

  • H2O2 and cisplatin treatments induced ROS production and apoptosis across four cancer cell types.
  • Antioxidant NAC partially reduced H2O2- and cisplatin-induced apoptosis.
  • Nuclear p-PKM2 levels were downregulated by H2O2 and cisplatin, with levels restored by NAC.

Conclusions:

  • PKM2 nuclear downregulation is associated with ROS-induced apoptosis in cancer cells.
  • PKM2 may serve as a potential therapeutic target for anticancer strategies.

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
4.6K
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
7.2K
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a...
5.3K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
5.1K
Electron Transport Chain: Complex I and II01:46

Electron Transport Chain: Complex I and II

The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
18.4K
Peroxisomes01:24

Peroxisomes

Peroxisomes are specialized organelles present in fungi, plant, and animal cells. It can vary in number, size, morphology, and activity depending on the type of tissue and the nutritional state of the cell. For example, cells with active lipid metabolism, such as adipocytes, neurons, and hepatocytes, have more peroxisomes than other cells in the body. Besides their primary role in breaking down complex organic molecules, peroxisomes can also synthesize specific macromolecules and participate in...
19.9K