D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects

Sayed, Salah Mohamed El; El-Magd, Rabab M Abou; Shishido, Yuji; Yorita, Kazuko; Chung, Seong Pil; Tran, Diem Hong; Sakai, Takashi; Watanabe, Hiroyoshi; Kubo, Shoji; Fukui, Kiyoshi

doi:10.1007/s10863-012-9455-y

Cited by 47 publications

(39 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results demonstrating the oxidative action of 3 BP were observed also upon its administration to human erythrocytes, glioma cells, hepatoma cells (SNU449 and Hep3B), breast cancer cells (MDA‐MB‐231, MDA‐MB‐435, and MCF‐7), and human promyelocytic leukemia cells (Calviño et al, ; El‐Sayed et al, ; Kim et al, ; Kwiatkowska et al, ; Sadowska‐Bartosz & Bartosz, ; Sadowska‐Bartosz, Soszyński, Ułaszewski, Ko, & Bartosz, ; Zhang et al, ). Most of the reactive oxygen species are generated as a result of the electron leakage from the electron transport chain to O 2 during mitochondrial respiration.…”

Section: Discussionsupporting

confidence: 65%

3‐Bromopyruvate as a potent anticancer therapy in honor and memory of the late Professor André Goffeau

Niedzwiecka

Casal

et al. 2018

Yeast

View full text Add to dashboard Cite

3-Bromopyruvate (3BP) is a small, highly reactive molecule formed by bromination of pyruvate. In the year 2000, the antitumor properties of 3BP were discovered. Studies using animal models proved its high efficacy for anticancer therapy with no apparent side effects. This was also found to be the case in a limited number of cancer patients treated with 3BP. Due to the "Warburg effect," most tumor cells exhibit metabolic changes, for example, increased glucose consumption and lactic acid production resulting from mitochondrial-bound overexpressed hexokinase 2. Such alterations promote cell migration, immortality via inhibition of apoptosis, and less dependence on the availability of oxygen. Significantly, these attributes also make cancer cells more sensitive to agents, such as 3BP that inhibits energy production pathways without harming normal cells. This selectivity of 3BP is mainly due to overexpressed monocarboxylate transporters in cancer cells. Furthermore, 3BP is not a substrate for any pumps belonging to the ATP-binding cassette superfamily, which confers resistance to a variety of drugs. Also, 3BP has the capacity to induce multiple forms of cell death, by, for example, ATP depletion resulting from inactivation of both glycolytic and mitochondrial energy production pathways. In addition to its anticancer property, 3BP also exhibits antimicrobial activity. Various species of microorganisms are characterized by different susceptibility to 3BP inhibition. Among tested strains, the most sensitive was found to be the pathogenic yeast-like fungus Cryptococcus neoformans. Significantly, studies carried out in our laboratories have shown that 3BP exhibits a remarkable capacity to eradicate cancer cells, fungi, and algae.

show abstract

Section: Discussionsupporting

confidence: 65%

3‐Bromopyruvate as a potent anticancer therapy in honor and memory of the late Professor André Goffeau

Niedzwiecka

Casal

et al. 2018

Yeast

View full text Add to dashboard Cite

show abstract

“…3-BP, which interacts with thiol and thiomethyl groups of cysteine and methionine residues [1], is a strong alkylating agent that inhibits both cellular ATP production sources of cancer cells, that is, glycolysis and mitochondrial pathways, while leaving normal cells unharmed [2][3][4]. 3-BP also inhibits the energy consuming process of angiogenesis, which is critical for cancer growth and metastasis [12]. 3-BP also inhibits the energy consuming process of angiogenesis, which is critical for cancer growth and metastasis [12].…”

Section: Introductionmentioning

confidence: 99%

Killing multiple myeloma cells with the small molecule 3-bromopyruvate

et al. 2014

View full text Add to dashboard Cite

The small molecule 3-bromopyruvate (3-BP), which has emerged recently as the first member of a new class of potent anticancer agents, was tested for its capacity to kill multiple myeloma (MM) cancer cells. Human MM cells (RPMI 8226) begin to lose viability significantly within 8 h of incubation in the presence of 3-BP. The Km (0.3 mmol/l) for intracellular accumulation of 3-BP in MM cells is 24 times lower than that in control cells (7.2 mmol/l). Therefore, the uptake of 3-BP by MM cells is significantly higher than that by peripheral blood mononuclear cells. Further, the IC50 values for human MM cells and control peripheral blood mononuclear cells are 24 and 58 µmol/l, respectively. Therefore, specificity and selectivity of 3-BP toward MM cancer cells are evident on the basis of the above. In MM cells the transcription levels of the gene encoding the monocarboxylate transporter MCT1 is significantly amplified compared with control cells. The level of intracellular ATP in MM cells decreases by over 90% within 1 h after addition of 100 µmol/l 3-BP. The cytotoxicity of 3-BP, exemplified by a marked decrease in viability of MM cells, is potentiated by the inhibitor of glutathione synthesis buthionine sulfoximine. In addition, the lack of mutagenicity and its superior capacity relative to Glivec to kill MM cancer cells are presented in this study.

show abstract

“…It is a powerful inhibitor of angiogenesis[20] and ATP-binding cassette transporters, which efflux chemotherapeutic drugs and cause chemoresistance[19]. Furthermore, 3BP inhibits key enzymes involved in glycolysis, including hexokinase II[17], glyceraldehyde-3-phosphate dehydrogenase[21], and LDH[22].…”

mentioning

confidence: 99%

Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study

Sayed¹,

Mohamed²,

Seddik³

et al. 2014

Chin J Cancer

View full text Add to dashboard Cite

3-Bromopyruvate (3BP) is a new, promising anticancer alkylating agent with several notable functions. In addition to inhibiting key glycolysis enzymes including hexokinase II and lactate dehydrogenase (LDH), 3BP also selectively inhibits mitochondrial oxidative phosphorylation, angiogenesis, and energy production in cancer cells. Moreover, 3BP induces hydrogen peroxide generation in cancer cells (oxidative stress effect) and competes with the LDH substrates pyruvate and lactate. There is only one published human clinical study showing that 3BP was effective in treating fibrolamellar hepatocellular carcinoma. LDH is a good measure for tumor evaluation and predicts the outcome of treatment better than the presence of a residual tumor mass. According to the Warburg effect, LDH is responsible for lactate synthesis, which facilitates cancer cell survival, progression, aggressiveness, metastasis, and angiogenesis. Lactate produced through LDH activity fuels aerobic cell populations inside tumors via metabolic symbiosis. In melanoma, the most deadly skin cancer, 3BP induced necrotic cell death in sensitive cells, whereas high glutathione (GSH) content made other melanoma cells resistant to 3BP. Concurrent use of a GSH depletor with 3BP killed resistant melanoma cells. Survival of melanoma patients was inversely associated with high serum LDH levels, which was reported to be highly predictive of melanoma treatment in randomized clinical trials. Here, we report a 28-year-old man presented with stage IV metastatic melanoma affecting the back, left pleura, and lung. The disease caused total destruction of the left lung and a high serum LDH level (4,283 U/L). After ethics committee approval and written patient consent, the patient received 3BP intravenous infusions (1-2.2 mg/kg), but the anticancer effect was minimal as indicated by a high serum LDH level. This may have been due to high tumor GSH content. On combining oral paracetamol, which depletes tumor GSH, with 3BP treatment, serum LDH level dropped maximally. Although a slow intravenous infusion of 3BP appeared to have minimal cytotoxicity, its anticancer efficacy via this delivery method was low. This was possibly due to high tumor GSH content, which was increased after concurrent use of the GSH depletor paracetamol. If the anticancer effectiveness of 3BP is less than expected, the combination with paracetamol may be needed to sensitize cancer cells to 3BP-induced effects.

show abstract

D-Amino acid oxidase-induced oxidative stress, 3-bromopyruvate and citrate inhibit angiogenesis, exhibiting potent anticancer effects

Cited by 47 publications

References 53 publications

3‐Bromopyruvate as a potent anticancer therapy in honor and memory of the late Professor André Goffeau

3‐Bromopyruvate as a potent anticancer therapy in honor and memory of the late Professor André Goffeau

Killing multiple myeloma cells with the small molecule 3-bromopyruvate

Safety and outcome of treatment of metastatic melanoma using 3-bromopyruvate: a concise literature review and case study

Contact Info

Product

Resources

About