Related Experiment Video

Updated: May 31, 2026

Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice
05:32

Multimodal Bioluminescent and Positronic-emission Tomography/Computational Tomography Imaging of Multiple Myeloma Bone Marrow Xenografts in NOG Mice

Published on: January 7, 2019

Cyclic AMP induces apoptosis in multiple myeloma cells and inhibits tumor development in a mouse myeloma model

Virginie Follin-Arbelet1, Peter O Hofgaard, Harald Hauglin

  • 1Department of Biochemistry, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway. virginie.follin-arbelet@medisin.uio.no

BMC Cancer
|July 20, 2011
PubMed
Abstract

Insights

Elevating cyclic adenosine monophosphate (cAMP) levels effectively kills multiple myeloma cells in vitro and inhibits tumor growth in vivo. This suggests targeting the cAMP pathway offers a promising therapeutic strategy for multiple myeloma.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Multiple myeloma is an incurable hematologic malignancy.
  • There is a clinical need for novel and effective therapeutic strategies.
  • The cyclic adenosine monophosphate (cAMP) signaling pathway is explored as a potential therapeutic target.

Purpose of the Study:

  • To investigate the potential of manipulating the cAMP signaling pathway to inhibit multiple myeloma cell growth.
  • To assess the efficacy of cAMP-elevating agents in preclinical models of multiple myeloma.

Main Methods:

  • Murine (MOPC315) and human (U266, INA-6) multiple myeloma cell lines were used for in vitro studies.
  • Cell death was analyzed via flow cytometry and western blot after treatment with cAMP-elevating agents (e.g., forskolin).
  • In vivo efficacy was evaluated using a murine model with subcutaneous MOPC315 tumors.

Main Results:

  • Forskolin significantly increased cell death in multiple myeloma cell lines, but not in control leukemia cells.
  • cAMP-mediated cell death exhibited hallmarks of apoptosis, including mitochondrial membrane potential changes and caspase activation.
  • Forskolin treatment inhibited multiple myeloma tumor growth in a preclinical mouse model.

Conclusions:

  • Elevating intracellular cAMP levels induces apoptosis in multiple myeloma cells.
  • Targeting the cAMP signaling pathway demonstrates therapeutic potential for inhibiting multiple myeloma progression.
  • Compounds that activate the cAMP pathway may represent a viable clinical strategy for treating multiple myeloma.

More Related Videos

Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells09:57

Real Time Detection of In Vitro Tumor Cell Apoptosis Induced by CD8+ T Cells to Study Immune Suppressive Functions of Tumor-infiltrating Myeloid Cells

Published on: January 29, 2019

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
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...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
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...