Wighteone is an antifungal agent with HSP90 and EGFRL858R/T790M inhibitory activities. Wighteone reduces HSP90 expression and blocks EGF-induced EGFR phosphorylation to inhibit ERK and AKT signaling. Wighteone induces cancer cell cycle redistribution, inhibits proliferation, and triggers apoptosis. Wighteone can be used in studies on HER2-positive breast cancer, leukemia, EGFRL858R/T790M non-small cell lung cancer, and fungal infections[1-4].
In vitro, UMR106 cells were treated with 50-500nM Wighteone for 48 hours. Wighteone promoted UMR106 cell proliferation[5]. NCI-H1975 cells were treated with 0.625-20μM Wighteone combined with 20ng/mL EGF for 48 hours. Wighteone inhibited NCI-H1975 cell proliferation and colony formation, and increased apoptosis[6]. MCF-7 human HER2-positive breast cancer cells were treated with 0.5-10mM Wighteone for 12-48 hours. Wighteone inhibited MCF-7 cell proliferation, increased apoptosis rate, and reduced HSP90 protein expression[7].
In vivo, male BALB/c nude mice xenografted with SW480 cells received 1-5mg/kg Wighteone by intravenous injection every two days for 22 days. Wighteone inhibited xenograft tumor growth, reduced tumor volume and weight, and decreased Akt phosphorylation in tumor tissues. Wighteone caused disorganized tumor cell arrangement, nuclear dissolution, and degenerative changes[8].
References:[1] Kalli S, Vallieres C, Violet J,et al. Cellular Responses and Targets in Food Spoilage Yeasts Exposed to Antifungal Prenylated Isoflavonoids. Microbiol Spectr. 2023 Aug 17;11(4):e0132723.
[2] Ngoh Misse Mouelle E, Foundikou Nsangou M, Fofack HMT, et al. In Vitro and In Silico Studies of the Biological Activities of Some Secondary Metabolites Belonging to Ficus sur Forssk (Moraceae): Towards Optimization of Wighteone Metabolite. Chem Biodivers. 2025 Jan;22(1):e202401270.
[3] Kumar S, Pathania AS, Saxena AK, et al. The anticancer potential of flavonoids isolated from the stem bark of Erythrina suberosa through induction of apoptosis and inhibition of STAT signaling pathway in human leukemia HL-60 cells. Chem Biol Interact. 2013 Oct 25;205(3):128-137.
[4] Lu X, Wu X, Jing L, et al. Network Pharmacology Analysis and Experiments Validation of the Inhibitory Effect of JianPi Fu Recipe on Colorectal Cancer LoVo Cells Metastasis and Growth. Evid Based Complement Alternat Med. 2020 Jul 26;2020:4517483.
[5] Xiaoli L, Naili W, Man Sau W, et al. Four New Isoflavonoids from the Stem Bark of Erythrina variegata. Chem Pharm Bull. 2006;54(4):570-573.
[6] Sun P, Qu Y, Wang Y, et al. Wighteone exhibits an antitumor effect against EGFR L858R/T790M mutation non-small cell lung cancer. J Cancer. 2021;12(13):3900-3908.
[7] Cao ZW, Zeng Q, Pei HJ, et al. HSP90 expression and its association with wighteone metabolite response in HER2-positive breast cancer cells. Oncol Lett. 2016 Jun;11(6):3719-3722.
[8] Chen X, Ma R, Wu W, et al. Wighteone, a prenylated flavonoid from licorice, inhibits growth of SW480 colorectal cancer cells by allosteric inhibition of Akt. J Ethnopharmacol. 2024 Sep 15;330:118195.