Benzaldehyde is a compound best known for its almond-like aroma. It can halt the growth and spread of pancreatic cancer cells. It is possible for those who have become resistant to standard treatments. Scientists from Fujita Health University in Japan have identified a mechanism by which benzaldehyde interferes with complex protein signaling pathways, suppressing tumor progression and resistance.

Benzaldehyde exerts its anticancer action by breaking the interaction between the signaling protein 14-3-3ζ and phosphorylated histone H3 at serine 28 (H3S28ph). Thus, this interference prevents the activation of genes involved in cancer cell survival, treatment resistance, and a process called epithelial-to-mesenchymal plasticity—a transformation that makes cancer cells more mobile and aggressive.

Targeting Pancreatic Cancer Resistance with Benzaldehyde

Pancreatic cancer is known for its aggressiveness and ability to evade treatment. As cancer cells transform from their original epithelial form into a more invasive mesenchymal state, they not only spread more easily but also become resistant to therapies. This transformation significantly hinders the effectiveness of conventional treatment methods.

To seek new ways to counteract this resistance, a team led by Dr. Hideyuki Saya, Director of the Oncology Innovation Center at Fujita Health University, explored the therapeutic properties of benzaldehyde.

Explaining the inspiration behind their work, Dr. Saya said, “In the 1980s, researchers demonstrated the anticancer activity of benzaldehyde and its derivatives. The first author of our study, Dr. Jun Saito, is the daughter of one of the researchers involved in those early studies, and she was driven by a strong desire to uncover the mechanism behind benzaldehyde’s anticancer effects.” The findings of their research were published online in the British Journal of Cancer on May 2, 2025.

Studies Confirm Benzaldehyde’s Anticancer Potential

Earlier studies had already suggested that benzaldehyde could hinder rapid cell growth by affecting the development of mouse embryonic cells. Building on this, the current study used a mouse model implanted with pancreatic cancer to investigate benzaldehyde’s therapeutic effects.

In lab-based cell culture experiments, benzaldehyde was shown to inhibit the growth of cancer cells that had developed resistance to both radiation therapy and osimertinib, a targeted drug that inhibits tyrosine kinases in growth factor signaling. Moreover, when combined with radiation, benzaldehyde was able to eliminate cells that had previously resisted radiation alone.

Protein Interactions for Overcoming Therapy Resistance

The research portrays that benzaldehyde prevents 14-3-3ζ from binding to H3S28ph. This is a protein interaction essential for activating genes that drive cancer cell survival and spread. By blocking this interaction, benzaldehyde reduces the expression of genes associated with treatment resistance and epithelial-to-mesenchymal transition. When it comes to mouse models, a benzaldehyde derivative significantly suppressed tumor growth. Further, prevented the cancer from spreading to distant organs like the lungs.

By interfering with a protein interaction, i.e., vital to cancer cell survival, benzaldehyde effectively overcomes resistance to therapy and inhibits metastasis. After knowing the broader significance of their findings, Dr. Saya noted, “The 14-3-3ζ protein has long been considered a target for cancer therapy, but its direct inhibition is not feasible due to its important functions in normal cells. Our results suggest that inhibition of the interaction between 14-3-3ζ and its client proteins by benzaldehyde has the potential to overcome the problem.”

The groundbreaking study highlights the promise of benzaldehyde as a valuable agent in combination cancer therapies. It is especially for treating tumors that no longer respond to radiation or tyrosine kinase inhibitors. In the coming years, benzaldehyde could play a vital role in enhancing the efficacy of existing molecular-targeted treatments.

Reference

DOI: 10.1038/s41416-025-03006-4

About Dr. Jun Saito from Fujita Health University

Dr. Jun Saito is a researcher at Fujita Health University’s Oncology Innovation Center. She has earned her Ph.D. from Nihon University. Building on her parents’ pioneering work, she uncovered the mechanism behind benzaldehyde’s anticancer effects, with expertise spanning oncology, immunology, and applied sciences.

Funding information

This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (KAKENHI 19K22568).

Original Publication
Authors: Jun Saito, Nobuyuki Onishi, Juntaro Yamasaki, Naoyoshi Koike, Yukie Hata, Kiyomi Kimura, Yuji Otsuki, Hiroyuki Nobusue, Oltea Sampetrean, Takatsune Shimizu, Shogo Okazaki, Eiji Sugihara and Hideyuki Saya.
Journal: British Journal of Cancer
DOI: 10.1038/s41416-025-03006-4
Method of Research: Experimental study
Subject of Research: Animals
Article Title: Benzaldehyde suppresses epithelial-mesenchymal plasticity and overcomes treatment resistance in cancer by targeting the interaction of 14-3-3ζ with H3S28ph
Article Publication Date: 2-May-2025
COI Statement: The authors declare no competing interests.

Original Source: https://www.fujita-hu.ac.jp/en/news/respr20250702.html