TY - JOUR
T1 - 3-Bromopyruvate as a potent anticancer therapy in honor and memory of the late Professor André Goffeau
AU - Ko, Young H.
AU - Niedźwiecka, Katarzyna
AU - Casal, Margarida
AU - Pedersen, Peter L.
AU - Ułaszewski, Stanisław
N1 - Funding Information:
Ministry of Science and Higher Education (Poland); Polish National Science Center (NCN), Grant/Award Number: UMO‐2015/ 19/N/NZ7/00956
Funding Information:
This study was supported by the Polish National Science Center (NCN), Preludium Grant UMO‐2015/19/N/NZ7/00956 (awarded to Katarzyna Niedźwiecka) and the Ministry of Science and Higher Education (Poland) within of “Statutory Research 2018/S/IGM.” Coauthors P. L. P. and Y. H. K. express their gratitude to Mr. Paul Edelman, The Oncology Foundation, Single Cause and Single Cure Foundation, Compassion Center, Dr. Ed Miller, and The G. Yu Foundation for their continued interest and support for our cancer research.
Funding Information:
This study was supported by the Polish National Science Center (NCN), Preludium Grant UMO-2015/19/N/NZ7/00956 (awarded to Katarzyna Nied?wiecka) and the Ministry of Science and Higher Education (Poland) within of ?Statutory Research 2018/S/IGM.? Coauthors P.?L.?P. and Y.?H.?K. express their gratitude to Mr. Paul Edelman, The Oncology Foundation, Single Cause and Single Cure Foundation, Compassion Center, Dr. Ed Miller, and The G. Yu Foundation for their continued interest and support for our cancer research.
Publisher Copyright:
© 2018 John Wiley & Sons, Ltd.
PY - 2019/4
Y1 - 2019/4
N2 - 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.
AB - 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.
KW - 3-bromopyruvate
KW - cancer therapy
KW - fungal infection
KW - melanoma
KW - metastasis
KW - multiple myeloma
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UR - http://www.scopus.com/inward/citedby.url?scp=85058483425&partnerID=8YFLogxK
U2 - 10.1002/yea.3367
DO - 10.1002/yea.3367
M3 - Article
C2 - 30462852
AN - SCOPUS:85058483425
SN - 0749-503X
VL - 36
SP - 211
EP - 221
JO - Yeast
JF - Yeast
IS - 4
ER -