07 Jul Japanese Scientists Discover How Simple A Compound from Almonds and Apricots May Have Anticancer Effects
MedicalResearch.com Interview with:
Dr. Hideyuki Saya, MD, PhD
Hideyuki Saya, MD, PhD
Director, Oncology Innovation Center
Fujita Health University
Toyoake, Japan
MedicalResearch.com: What is the background for this study?
Response: Benzaldehyde, a simple aromatic compound found in the natural aroma of almonds and apricots, has long been reported to have anticancer activity, with clinical trials even conducted in Japan in the 1980s. However, the molecular mechanism underlying its anticancer effect has remained unclear for decades.
Our study was initiated by Dr. Jun Saito, whose father was one of the original researchers studying benzaldehyde. Driven by a personal motivation to clarify the scientific basis of this compound’s effect, Dr. Saito spent over a decade in our lab to finally uncover its mechanism of action.
MedicalResearch.com: What are the main findings?
Response: We discovered that benzaldehyde exerts its anticancer effect by targeting 14-3-3ζ, a key intracellular protein that coordinates multiple oncogenic signaling pathways. Specifically, benzaldehyde disrupts the interaction between 14-3-3ζ and histone H3 phosphorylated at serine 28 (H3S28ph), a complex implicated in cancer cell plasticity, stemness, and treatment resistance. This disruption led to the suppression of epithelial-mesenchymal plasticity (EMP), reduction in cancer stem-like properties, and the re-sensitization of cancer cells resistant to tyrosine kinase inhibitors and radiation therapy. Furthermore, treatment with a benzaldehyde derivative significantly inhibited tumor growth and metastasis in a pancreatic cancer mouse model.
MedicalResearch.com: What should readers take away from your report?
Response: Our findings suggest that even simple natural compounds like benzaldehyde can have profound biological effects by targeting crucial protein-protein interactions in cancer. Importantly, 14-3-3ζ appears to function as a molecular hub integrating multiple signals related to tumor aggressiveness and resistance. Inhibiting this hub offers a promising strategy for overcoming treatment resistance and suppressing metastasis. The study also highlights the importance of revisiting earlier drug candidates with modern scientific tools to uncover previously unrecognized mechanisms.
MedicalResearch.com: What recommendations do you have for future research as a results of this study?
Response: Future research should focus on optimizing benzaldehyde derivatives for better pharmacokinetic properties and specificity, as well as validating the clinical relevance of targeting 14-3-3ζ in different cancer types. We also envision combining 14-3-3ζ inhibitors with existing therapies such as EGFR inhibitors or radiation to enhance their efficacy in resistant tumors. Additionally, understanding the broader interactome of 14-3-3ζ may reveal new pathways of therapeutic interest.
No conflicts of interest are declared.
Citation: Saito, J., Onishi, N., Yamasaki, J. et al. Benzaldehyde suppresses epithelial-mesenchymal plasticity and overcomes treatment resistance in cancer by targeting the interaction of 14-3-3ζ with H3S28ph. Br J Cancer (2025). https://doi.org/10.1038/s41416-025-03006-4
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Last Updated on July 8, 2025 by Marie Benz MD FAAD
