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Updated: Jun 23, 2026
Application of Retinoic Acid to Obtain Osteocytes Cultures from Primary Mouse Osteoblasts
Published on: May 13, 2014
Fenretinide inhibits myeloma cell growth, osteoclastogenesis and osteoclast viability
Xin Li1, Wen Ling, Angela Pennisi
1Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. lixin@uams.edu
Abstract:
Fenretinide (4HPR), a nontoxic analog of ATRA, has been investigated in various malignancies but not in multiple myeloma (MM), a plasma cell malignancy associated with induction of osteolytic bone disease. Here we show that 4HPR induces apoptosis through increased level of ROS and activation of caspase-8, 9 and 3, and inhibits growth of several MM cell lines in a dose-dependent manner. Serum or co-culture with the supportive osteoclasts partially protects MM cells from 4HPR-induced growth inhibition. Sphingosine-1 phosphate (S1P) significantly protects MM cells from 4HPR-induced apoptosis suggesting that as in other malignancies, this drug up-regulates ceramide in MM cells. 4HPR has no toxic effects on non-malignant cells such as blood mononucleated cells, mesenchymal stem cells and osteoblasts, but markedly reduces viability of endothelial cells and mature osteoclasts and inhibits differentiation of osteoclasts and MM-induced tube formation. 4HPR is a potential anti-MM agent, affecting MM cells and MM-induced bone disease and angiogenesis.
Insights
Fenretinide (4HPR) effectively inhibits multiple myeloma (MM) cell growth and induces apoptosis. This agent also targets MM-associated bone disease and angiogenesis with minimal toxicity to healthy cells.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Multiple myeloma (MM) is a plasma cell malignancy characterized by osteolytic bone disease.
- Fenretinide (4HPR), a synthetic retinoid analog, has shown efficacy in various cancers but its role in MM is unexplored.
- Understanding novel therapeutic targets for MM is crucial.
Purpose of the Study:
- To investigate the efficacy of Fenretinide (4HPR) as a potential therapeutic agent against multiple myeloma (MM).
- To elucidate the mechanisms of action of 4HPR in MM cells and its effects on the tumor microenvironment.
- To assess the safety and toxicity profile of 4HPR in relevant cell types.
Main Methods:
- In vitro studies using multiple myeloma (MM) cell lines.
- Assessment of apoptosis induction via reactive oxygen species (ROS) and caspase activation.
- Evaluation of 4HPR's effects on cell viability, osteoclast differentiation, and angiogenesis.
Main Results:
- 4HPR demonstrated dose-dependent inhibition of MM cell growth and induced apoptosis through ROS and caspase pathways.
- Serum and osteoclasts partially mitigated 4HPR's growth inhibitory effects, while S1P protected against apoptosis.
- 4HPR exhibited no toxicity to non-malignant cells but reduced endothelial cell and osteoclast viability, inhibiting osteoclast differentiation and angiogenesis.
Conclusions:
- Fenretinide (4HPR) is a promising agent against multiple myeloma (MM), impacting both cancer cells and associated bone disease.
- 4HPR's mechanism involves apoptosis induction and anti-angiogenic effects.
- The drug's selective toxicity profile suggests potential for clinical application in MM treatment.
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