The potential role of formononetin in cancer treatment: An updated review

• Published in: Biomedicine & pharmacotherapy 2023-12, Vol.168, p.115811-115811, Article 115811
• Main Authors: Aliya, Sheik, Alhammadi, Munirah, Park, Uichang, Tiwari, Jitendra N., Lee, Jeong-Hwan, Han, Young-Kyu, Huh, Yun Suk
• Format: Article
• Language: English
• Subjects: Anticancer activity; Formononetin; Molecular mechanism; Signaling pathway; Tumor
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2023.115811

Currently, cancer is one of the main research topics, due to its high incidence and drug resistance to existing anti-cancer drugs. Formononetin, a natural product with phytoestrogenic properties and diverse biological functions, has attracted the attention of researchers working on anticancer drugs. Formononetin emerges as an intriguing bioactive substance compared to other isoflavones as it exhibits potent chemotherapeutic activity with less toxicity. Formononetin effectively plays a significant role in inhibiting cell proliferation, invasion, and metastatic abilities of cancer cells by targeting major signaling pathways at the junction of interconnected pathways. It also induces apoptosis and cell cycle arrest by modulating mediator proteins. It causes upregulation of key factors such as p-AKT, p38, p21, and p53 and downregulation of NF-κB. Furthermore, formononetin regulates the neoplastic microenvironment by inactivating the ERK1/2 pathway and lamin A/C signaling and has been reported to inactivate JAK/STAT, PKB or AKT, and mitogen-activated protein kinase pathways and to suppress cell migration, invasion, and angiogenesis in human cancer cells. To assist researchers in further exploring formononetin as a potential anticancer therapeutic candidate, this review focuses on both in vitro and in vivo proof of concept studies, patents, and clinical trials pertinent to formononetin's anticancer properties. Overall, this review discusses formononetin from a comprehensive perspective to highlight its potential benefits as an anticancer agent. [Display omitted] •Formononetin, a phytoestrogen isoflavonoid found in a wide range of food plants and therapeutic herbs.•Formononetin exhibits numerous biological and pharmacological effects.•Formononetin significantly reduces the detrimental toxic effects caused by chemotherapeutic drugs.•Identifying formononetin's specific targets and pathways is crucial.•Formononetin is a promising agent to treat various types of cancers and tumors.