Menadione is a metabolite of oral vitamin K with cytotoxicity [1]. The oxidative stress induced by Menadione in isolated liver cells leads to the depletion of soluble sulfhydryl groups and protein sulfhydryl groups, and causes changes in intracellular Ca2+ homeostasis. [2]. Menadione has been widely used to induce mitochondrial depolarization and promote apoptosis in various cells [3].
In vitro, Menadione treatment for 24 hours significantly inhibited the growth of ARIP cells, with an IC50 value of 42.1μM [4]. Treatment with 5μM Menadione for 96 hours significantly inhibited the viability of MCF-7 cells and increased the level of reactive oxygen species (ROS) [5]. Treatment with 100μM Menadione for 72 hours significantly induced cell necrosis in AR4-2J cells, accompanied by DNA fragmentation[6].
In vivo, Menadione treatment via a single intraperitoneal injection at a dose of 10mg/kg alleviated acute pancreatitis (AP) and associated lung damage in mice induced by secretin within 6 hours [7]. Intraperitoneal injection of Menadione at a dose of 10mg/kg twice weekly for 4 weeks significantly inhibited the growth of UACC903 melanoma in mice[8].
References:
[1] Thijssen H H W, Vervoort L M T, Schurgers L J, et al. Menadione is a metabolite of oral vitamin K[J]. British Journal of Nutrition, 2006, 95(2): 260-266.
[2] Di Monte D, Bellomo G, Thor H, et al. Menadione-induced cytotoxicity is associated with protein thiol oxidation and alteration in intracellular Ca2+ homeostasis[J]. Archives of Biochemistry and Biophysics, 1984, 235(2): 343-350.
[3] Gerasimenko J V, Gerasimenko O V, Palejwala A, et al. Menadione-induced apoptosis: roles of cytosolic Ca2+ elevations and the mitochondrial permeability transition pore[J]. Journal of Cell Science, 2002, 115(3): 485-497.
[4] Osada S, Tomita H, Tanaka Y, et al. The utility of vitamin K3 (menadione) against pancreatic cancer[J]. Anticancer research, 2008, 28(1A): 45-50.
[5] Marchionatti A M, Picotto G, Narvaez C J, et al. Antiproliferative action of menadione and 1, 25 (OH) 2D3 on breast cancer cells[J]. The Journal of steroid biochemistry and molecular biology, 2009, 113(3-5): 227-232.
[6] Sata N, Klonowski-Stumpe H, Han B, et al. Menadione induces both necrosis and apoptosis in rat pancreatic acinar AR4-2J cells[J]. Free Radical Biology and Medicine, 1997, 23(6): 844-850.
[7] Tamizhselvi R, Manickam V. Menadione (vitamin K3) inhibits hydrogen sulfide and substance P via NF-кB pathway in caerulein-induced acute pancreatitis and associated lung injury in mice[J]. Pancreatology, 2019, 19(2): 266-273.
[8] Shah M, Stebbins J L, Dewing A, et al. Inhibition of Siah2 ubiquitin ligase by vitamin K3 (menadione) attenuates hypoxia and MAPK signaling and blocks melanoma tumorigenesis[J]. Pigment cell & melanoma research, 2009, 22(6): 799-808.