Are there natural products that target the proteasome to help treat Multiple Myeloma?

Multiple myeloma is a blood cancer that often requires treatment with proteasome inhibitors, which block a cell's protein recycling system. While several natural products have been found to target the proteasome, none are currently approved as standalone treatments for multiple myeloma. The most advanced natural product-derived drug is marizomib, which is still being tested in clinical trials ²⁹¹⁰. Other natural compounds, such as polyphenols found in plants, have shown anti-myeloma effects in lab studies, but they are not a substitute for standard medical therapy ¹¹.

What the research says

A 2025 narrative review highlights that natural products can directly inhibit the proteasome or make myeloma cells more sensitive to existing proteasome inhibitors ². One natural product, marizomib (also known as salinosporamide A), has advanced to clinical trials for multiple myeloma ²⁹¹⁰. Marizomib is derived from a marine bacterium and is not peptide-based, unlike synthetic inhibitors such as bortezomib ⁹¹⁰. However, marizomib is not yet FDA-approved for any indication.

Other natural products, like lactacystin, also inhibit the proteasome but are primarily used as research tools rather than treatments ⁹¹⁰. A 2019 study on natural polyphenols (found in fruits, vegetables, and herbs) reported that these compounds can induce apoptosis (cell death) in myeloma cells and may have low toxicity toward normal cells ¹¹. However, these findings come from laboratory experiments, not large human trials.

It is important to note that standard multiple myeloma treatments include FDA-approved proteasome inhibitors such as bortezomib, carfilzomib, and ixazomib, as well as immunomodulatory drugs like lenalidomide and pomalidomide ¹³⁴⁵. These drugs have proven benefits in clinical trials, whereas natural products have not yet been shown to be effective treatments on their own.

What to ask your doctor

• Are there any clinical trials for marizomib or other natural product-derived proteasome inhibitors that I might be eligible for?
• Could natural supplements like polyphenols interfere with my current multiple myeloma treatment?
• What is the evidence that natural products can help treat multiple myeloma, and are they safe to use alongside standard therapies?
• Should I consider any dietary changes or supplements as part of my treatment plan, or are they unlikely to help?
• How do approved proteasome inhibitors like bortezomib or carfilzomib compare to natural product-based options in terms of effectiveness and side effects?