Related Experiment Video

Updated: May 13, 2026

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates
09:47

Evaluation of Substrate Ubiquitylation by E3 Ubiquitin-ligase in Mammalian Cell Lysates

Published on: May 10, 2022

Pentoxifylline and the proteasome inhibitor MG132 induce apoptosis in human leukemia U937 cells through a decrease in

Alejandro Bravo-Cuellar1, Georgina Hernández-Flores, José Manuel Lerma-Díaz

  • 1División de Inmunología, Centro de Investigación Biomédica de Occidente CIBO, Instituto Mexicano del Seguro Social IMSS, Sierra Mojada 800, Col, Independencia, Guadalajara, Jalisco 44340, México.

Journal of Biomedical Science
|March 1, 2013
PubMed
Abstract

Insights

Chemotherapy resistance in leukemia is a major challenge. PTX and MG132 drugs, by disrupting the NF-κB pathway, induce apoptosis and enhance anti-leukemic effects in U937 cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Chemotherapy resistance in cancer, particularly leukemia, remains a significant clinical challenge.
  • The nuclear factor-kappa B (NF-κB) pathway is implicated in tumor survival and chemoresistance by regulating antiapoptotic proteins.
  • U937 human leukemia cells were used to investigate novel therapeutic strategies targeting the NF-κB pathway.

Purpose of the Study:

  • To evaluate the effects of PTX and MG132, agents that disrupt the NF-κB pathway, on U937 leukemia cells.
  • To assess the combined efficacy of PTX and MG132 in overcoming chemoresistance.
  • To elucidate the molecular mechanisms underlying their cytotoxic and apoptotic effects.

Main Methods:

  • Cell viability assays, apoptosis detection, and cell cycle analysis were performed.
  • Key apoptotic markers including caspases -3, -8, -9, and cytochrome c release were measured.
  • Mitochondrial membrane potential, p65 phosphorylation, and expression of pro-/anti-apoptotic genes were analyzed.

Main Results:

  • Both PTX and MG132 demonstrated time-dependent cytotoxicity and induced apoptosis in U937 cells.
  • Combined drug treatment resulted in the greatest apoptotic effect and G1 phase cell cycle arrest.
  • The drugs decreased p65 phosphorylation and levels of antiapoptotic proteins Bcl-2 and Bcl-XL, while upregulating proapoptotic genes (BAX, DIABLO, FAS).

Conclusions:

  • PTX and MG132 exhibit individual and synergistic antileukemic potential by inducing apoptosis and cell cycle arrest.
  • The observed effects are linked to caspase activation, decreased NF-κB signaling, and modulation of Bcl-2 family proteins.
  • Combination therapy shows promise for overcoming chemoresistance by shifting the balance towards apoptosis in leukemia cells.

Related Concept Videos

The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
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 daughter...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
Cellular Injury V: Apoptosis and Autophagy01:22

Cellular Injury V: Apoptosis and Autophagy

Cells respond to damage and stress through highly coordinated processes that decide whether they survive or undergo controlled self-destruction. Two major pathways involved in this regulation are apoptosis, a type of programmed cell death, and autophagy, a survival mechanism that helps cells adapt to adverse conditions.ApoptosisApoptosis removes aged or injured cells to maintain tissue balance. During this process, the cell shrinks, chromatin condenses and fragments, and membrane-bound...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.