Saito Jun, Onishi Nobuyuki, Yamasaki Juntaro, Koike Naoyoshi, Hata Yukie, Kimura Kiyomi, Otsuki Yuji, Nobusue Hiroyuki, Sampetrean Oltea, Shimizu Takatsune, Okazaki Shogo, Sugihara Eiji, Saya Hideyuki
Oncology Innovation Center, Fujita Health University, Toyoake, Aichi, 470-1192, Japan.
Department of Pathophysiology, Hoshi University, Shinagawa, Tokyo, 142-0063, Japan.
Br J Cancer. 2025 May 2. doi: 10.1038/s41416-025-03006-4.
Benzaldehyde (BA) is an aromatic aldehyde found in fruits that has been studied as a potential anticancer agent on the basis of its ability to inhibit transformation in mouse embryo cells and to suppress metastasis in mice.
We investigated the cytotoxic effects of BA on cancer cells, and probed its effects on intracellular signaling pathways. The anticancer effects of BA in vivo were studied by using a mouse orthotopic transplantation model of pancreatic cancer.
BA inhibited the growth of osimertinib- or radiation-resistant cancer cells as well as the interaction between 14-3-3ζ and its client proteins. The interaction of 14-3-3ζ with the Ser-phosphorylated form of histone H3 (H3S28ph) was implicated in treatment resistance and the transcriptional regulation of genes related to epithelial-mesenchymal transition and stemness, including E2F2, SRSF1, and ID1. Treatment of mice with a BA derivative inhibited pancreatic tumor growth and lung metastasis, as well as suppressed a state of epithelial-mesenchymal plasticity (EMP) of tumor cells.
The interaction between 14-3-3ζ and H3S28ph plays a key role in EMP and treatment resistance in cancer. The ability of BA to inhibit this and other interactions of 14-3-3ζ offers the potential to overcome treatment resistance and to suppress metastasis.
苯甲醛（BA）是一种存在于水果中的芳香醛，基于其抑制小鼠胚胎细胞转化和抑制小鼠转移的能力，已被作为一种潜在的抗癌剂进行研究。
我们研究了BA对癌细胞的细胞毒性作用，并探究了其对细胞内信号通路的影响。通过使用胰腺癌小鼠原位移植模型研究了BA在体内的抗癌作用。
BA抑制了奥希替尼或放疗抗性癌细胞的生长以及14-3-3ζ与其客户蛋白之间的相互作用。14-3-3ζ与组蛋白H3的丝氨酸磷酸化形式（H3S28ph）的相互作用与治疗抗性以及与上皮-间质转化和干性相关的基因（包括E2F2、SRSF1和ID1）的转录调控有关。用BA衍生物治疗小鼠可抑制胰腺肿瘤生长和肺转移，并抑制肿瘤细胞的上皮-间质可塑性（EMP）状态。
14-3-3ζ与H3S28ph之间的相互作用在癌症的EMP和治疗抗性中起关键作用。BA抑制14-3-3ζ的这种及其他相互作用的能力为克服治疗抗性和抑制转移提供了潜力。
