Verrucarin J

Verrucarin J is a macrocyclic trichothecene that has been found in A. verrucaria and has fungicidal and anticancer activities.^1,2,3 It is active against a variety of plant pathogenic fungi, including B. cinerea, C. coccodes, F. oxysporum, and M. oryzae (MICs = 12.5, 6.3, 50, and 12.5 µg/ml, respectively).¹ Verrucarin J reduces viability of A549 and NCI H1793 human non-small cell lung cancer (NSCLC) cells (IC₅₀s = 10 and 20 nM, respectively) and induces apoptosis in A549 cells when used at concentrations ranging from 10 to 50 nM.² It reduces the expression of the cancer stem cell genes encoding ALDH1, LGR5, Oct4, and prominin-1, also known as CD133, as well as the Wnt signaling genes encoding Wnt1, β-catenin, Tcf4, and Notch1 in A549 cells. Verrucarin J also reduces the viability, invasion, and migration of HCT116 human colorectal cancer cells overexpressing Akt (Akt/HCT116 cells).³ It reduces tumor growth in an Akt/HCT116 mouse xenograft model when administered at a dose of 0.5 mg/kg.

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1. Nguyen, M.V., Han, J.W., Kim, H., et al. Curvicollide D, a new modified γ-lactone from the culture broth of Albifimbria verrucaria and its antifungal activity against plant pathogenic fungi. J. Antibiot. (Tokyo) 75(9), 514-518 (2022).

2. Udoh, K., Parte, S., Carter, K., et al. Targeting of lung cancer stem cell self-renewal pathway by a small molecule verrucarin J. Stem Cell Rev. Rep. 15(4), 601-611 (2019).

3. Pal, D., Tyagi, A., Chandrasekaran, B., et al. Suppression of Notch1 and AKT mediated epithelial to mesenchymal transition by verrucarin J in metastatic colon cancer. Cell Death Dis. 9(8), 798 (2018).