Related Experiment Video

Updated: Mar 21, 2026

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer
06:51

Utilizing 18F-FDG PET/CT Imaging and Quantitative Histology to Measure Dynamic Changes in the Glucose Metabolism in Mouse Models of Lung Cancer

Published on: July 21, 2018

18.8K

MDM2 antagonist nutlin-3a sensitizes tumors to V-ATPase inhibition

Lina S Schneider1, Melanie Ulrich1, Thorsten Lehr2

  • 1Department of Pharmacy, Pharmaceutical Biology, Ludwig-Maximilians-University of Munich, Butenandtstrasse 5-13, 81377 Munich, Germany.

Molecular Oncology
|May 10, 2016
PubMed

Insights

Combining archazolid with nutlin-3a synergistically kills cancer cells by targeting p53 wild type tumors. This combination therapy reduces tumor growth more effectively than single treatments in preclinical models.

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Therapeutics

Background:

  • Cancer treatment faces challenges with single-agent chemotherapy due to tumor mutations.
  • The tumor suppressor p53 is frequently mutated, driving interest in p53-targeting therapies.
  • V-ATPase inhibition by archazolid increases p53 protein levels in cancer cells.

Purpose of the Study:

  • To investigate the synergistic effect of combining archazolid and nutlin-3a in p53 wild type cancer.
  • To elucidate the underlying mechanisms of the combined therapeutic effect.
  • To evaluate the in vivo efficacy of the combination therapy.

Main Methods:

  • Combination treatment of cancer cell lines with archazolid and nutlin-3a.
  • Analysis of apoptosis, glycolysis, and related protein/mRNA levels.
  • In vivo studies using a U87MG mouse xenograft model.

Main Results:

  • Archazolid and nutlin-3a synergistically induced cell death in p53 wild type tumor cell lines.
  • Combination therapy reduced glycolysis, evidenced by decreased glucose uptake and Glut1 levels, and increased TIGAR mRNA.
  • Pro-apoptotic pathways (IGFBP3, Bax) were activated, leading to caspase-9 and PARP cleavage.
  • In vivo, the combination significantly inhibited tumor growth compared to single agents.

Conclusions:

  • The combination of archazolid and nutlin-3a shows synergistic anti-cancer activity in p53 wild type tumors.
  • This combination impacts glycolysis and activates apoptosis, offering a novel therapeutic strategy.
  • Archazolid and nutlin-3a represent a promising combination for treating p53 wild type cancers.
Keywords:
CancerNutlin-3aTherapyV-ATPasep53

More Related Videos

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics12:28

Establishing Cell Lines Overexpressing DR3 to Assess the Apoptotic Response to Anti-mitotic Therapeutics

Published on: January 11, 2019

7.8K
Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

3.2K

Related Concept Videos

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...
5.4K
Drugs that Destabilize Microtubules01:10

Drugs that Destabilize Microtubules

Microtubules are dynamic structures and can be regulated by microtubule targeting agents (MTAs). Microtubule destabilizing drugs are a class of MTAs that destabilize and prevent microtubules' polymerization. Both natural and synthetic chemicals can be found under this class of drugs. Vincristine and vinblastine, two vinca alkaloids, and colchicine were among the first to be discovered. These drugs can affect cells in various ways, either by inducing a change in cell morphology, preventing...
4.2K
Drugs that Stabilize Microtubules01:15

Drugs that Stabilize Microtubules

Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.9K
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...
5.0K
Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists01:29

Chemotherapy-Induced Nausea and Vomiting: Dopamine Receptor Antagonists

Dopamine receptor antagonists, also known as antipsychotic agents, are critical in managing chemotherapy-induced vomiting. These antiemetic agents block dopamine receptors in the chemoreceptor trigger zone (CTZ), inhibiting signal transmission to the vomiting center. Antipsychotic agents encompass phenothiazines (PTZ), butyrophenones, benzamides, and thienobenzodiazepines (Zyprexa), which are utilized for their antiemetic and sedative properties.
Phenothiazines, such as prochlorperazine...
1.0K
Treatment Resistant Cancers02:56

Treatment Resistant Cancers

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...
3.9K