title: Mechanisms underlying 3-bromopyruvate-induced cell death in colon cancer.
abstract: 3-Bromopyruvate (3BP) is an energy-depleting drug that inhibits Hexokinase II activity by alkylation during glycolysis, thereby suppressing the production of ATP and inducing cell death. As such, 3BP can potentially serve as an anti-tumorigenic agent. Our previous research showed that 3BP can induce apoptosis via AKT /protein Kinase B signaling in breast cancer cells. Here we found that 3BP can also induce colon cancer cell death by necroptosis and apoptosis at the same time and concentration in the SW480 and HT29 cell lines; in the latter, autophagy was also found to be a mechanism of cell death. In HT29 cells, combined treatment with 3BP and the autophagy inhibitor 3-methyladenine (3-MA) exacerbated cell death, while viability in 3BP-treated cells was enhanced by concomitant treatment with the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (z-VAD-fmk) and the necroptosis inhibitor necrostatin (Nec)-1. Moreover, 3BP inhibited tumor growth in a SW480 xenograft mouse model. These results indicate that 3BP can suppress tumor growth and induce cell death by multiple mechanisms at the same time and concentration in different types of colon cancer cell by depleting cellular energy stores.
authors.affiliation: Faculty of Pharmacy, Bengbu Medical College, Bengbu, 233000, Anhui, People's Republic of China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Sun
authors.forename: Zhe
authors.initials: Z
authors.lastname: Liu
authors.forename: Xue
authors.initials: X
authors.lastname: Zou
authors.forename: Yadong
authors.initials: Y
authors.lastname: Lan
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Sun
authors.forename: Xiu
authors.initials: X
authors.lastname: Wang
authors.forename: Surong
authors.initials: S
authors.lastname: Zhao
authors.forename: Chenchen
authors.initials: C
authors.lastname: Jiang
authors.forename: Hao
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D011773:Pyruvates / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D011773:Pyruvates; C017092:bromopyruvate