3-Bromopyruvate induces apoptosis in breast cancer cells by downregulating Mcl-1 through the PI3K/Akt signaling pathway

Liu, Zhe; Zhang, Yuanyuan; Zhang, Qianwen; Song, Zhao; Wu, Cheng‐Zhu; Cheng, Xiangdong; Jiang, Chenchen; Jiang, Zhiwen; Líu, Hao

doi:10.1097/cad.0000000000000081

Cited by 33 publications

(21 citation statements)

References 26 publications

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“…For endometrial cancer, 3-BP induced tumor necrosis in vitro and inhibited tumor growth in vivo [64]. It has also been reported that 3-BP induced apoptosis in MDA-MB-231 breast cancer cells by downregulating Mcl-1 through the PI3K/Akt signaling pathway, which is upstream of HK-II [65]. Recently, Gandham et al also showed that liposomal 3-BP improved permeability, HK-II inhibition, and cytotoxicity in a multicellular spheroid model of human ovarian adenocarcinoma (SKOV-3) cells [66, 67].…”

Section: Agents Targeted Inhibiting the Hk-ii-mediated Warburg Effectmentioning

confidence: 99%

Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma

Zhong

Zhou

2016

Oncotarget

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Radiotherapy is now widely used as a part of multidisciplinary treatment approaches for advanced laryngeal carcinoma and preservation of laryngeal function. However, the mechanism of the radioresistance is still unclear. Some studies have revealed that the Warburg effect promotes the radioresistance of various malignant tumors, including laryngeal carcinoma. Among the regulators involved in the Warburg effect, hexokinase-II (HK-II) is a crucial glycolytic enzyme that catalyzes the first essential step of glucose metabolism. HK-II is reportedly highly expressed in some human solid carcinomas by many studies. But for laryngeal carcinoma, there is only one. Till now, no studies have directly targeted inhibited HK-II and enhanced the radiosensitivity of laryngeal carcinoma. Accumulating evidence has shown that dysregulated signaling pathways often result in HK-II overexpression. Here, we summarize recent advances in understanding the association among the Warburg effect, HK-II, and the radioresistance of laryngeal carcinoma. We speculate on the feasibility of enhancing radiosensitivity by targeted inhibiting HK-II signaling pathways in laryngeal carcinoma, which may provide a novel anticancer therapy.

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Section: Agents Targeted Inhibiting the Hk-ii-mediated Warburg Effectmentioning

confidence: 99%

Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma

Zhong

Zhou

2016

Oncotarget

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“…While mitochondria silencing has long been accepted as general consensus in cancer cells (Warburg effect), recent studies revealed that this intracellular network is still functional, even in cells that shifted cellular energy metabolism to glycolysis [62]. Hence, a potential therapeutic strategy may consist in the re-activation of mitochondrial oxidative metabolism, including by inhibiting glycolysis [63-64]. Interestingly, the glycolytic phenotype of cancer cells has been reported to be induced by Akt upregulation [65].…”

Section: Discussionmentioning

confidence: 99%

ROS-mediated EB1 phosphorylation through Akt/GSK3β pathway: implication in cancer cell response to microtubule-targeting agents

et al. 2014

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Microtubule-targeting agents (MTAs) are largely administered in adults and children cancers. Better deciphering their mechanism of action is of prime importance to develop more convenient therapy strategies. Here, we addressed the question of how reactive oxygen species (ROS) generation by mitochondria can be necessary for MTA efficacy. We showed for the first time that EB1 associates with microtubules in a phosphorylation-dependent manner, under control of ROS. By using phospho-defective mutants, we further characterized the Serine 155 residue as critical for EB1 accumulation at microtubule plus-ends, and both cancer cell migration and proliferation. Phosphorylation of EB1 on the Threonine 166 residue triggered opposite effects, and was identified as a requisite molecular switch in MTA activities. We then showed that GSK3β activation was responsible for MTA-triggered EB1 phosphorylation, resulting from ROS-mediated inhibition of upstream Akt. We thus disclosed here a novel pathway by which generation of mitochondrial ROS modulates microtubule dynamics through phosphorylation of EB1, improving our fundamental knowledge about this oncogenic protein, and pointing out the need to re-examine the current dogma of microtubule targeting by MTAs. The present work also provides a strong mechanistic rational to the promising therapeutic strategies that currently combine MTAs with anti-Akt targeted therapies.

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“…anti-tumor effect in vivo 18 . The researches of anti-cancer effects of 3BP had a good foundation of papers.…”

Section: Discussionmentioning

confidence: 99%

Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice

Pan¹,

Sun²,

Jin³

et al. 2016

Acta Cir. Bras.

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PURPOSE:To investigate the hepatotoxicity and nephrotoxicity of 3-Bromopyruvate (3BP) in mice. hours later, the blood were used for the determination of hepatic damage serum biomarkers. Livers were stored in 4 % formalin solution for the later detection. METHODS: RESULTS:3BP at the dose of 8mg/kg had a good effect on inhibiting tumor growth in nude mice and did not damage liver and kidney tissues. Kunming mice experiment showed 3BP at the dose of 16mg/kg did damage to liver tissues. CONCLUSION:3-Bromopyruvate at the dose of suppressing tumor growth did not exhibit hepatotoxicity and nephrotoxicity in nude mice, and the effect on liver was confirmed in Kunming mice.

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3-Bromopyruvate induces apoptosis in breast cancer cells by downregulating Mcl-1 through the PI3K/Akt signaling pathway

Cited by 33 publications

References 26 publications

Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma

Warburg effect, hexokinase-II, and radioresistance of laryngeal carcinoma

ROS-mediated EB1 phosphorylation through Akt/GSK3β pathway: implication in cancer cell response to microtubule-targeting agents

Hepatotoxicity and nephrotoxicity of 3-bromopyruvate in mice

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