Syrosingopine sensitizes cancer cells to killing by metformin

被引：64

作者：

Benjamin, Don ^{[1
]}

Colombi, Marco ^{[1
]}

Hindupur, Sravanth K. ^{[1
]}

Betz, Charles ^{[1
]}

Lane, Heidi A. ^{[2
]}

El-Shemerly, Mahmoud Y. M. ^{[2
]}

Lu, Min ^{[3
]}

Quagliata, Luca ^{[4
]}

Terracciano, Luigi ^{[4
]}

Moes, Suzette ^{[1
]}

Sharpe, Timothy ^{[1
]}

Wodnar-Filipowicz, Aleksandra ^{[5
]}

Moroni, Christoph ^{[1
]}

Hall, Michael N. ^{[1
]}

机构：

[1] Univ Basel, Biozentrum, CH-4056 Basel, Switzerland

[2] Basilea Pharmaceut Int Ltd, Basel, Switzerland

[3] Univ Basel, Inst Med Microbiol, CH-4003 Basel, Switzerland

[4] Univ Basel Hosp, Mol Pathol, CH-4003 Basel, Switzerland

[5] Univ Basel, Stem Cell Ctr Competence, CH-4056 Basel, Switzerland

来源：

SCIENCE ADVANCES | 2016年 / 2卷 / 12期

基金：

瑞士国家科学基金会;

关键词：

NEURON-SPECIFIC ENOLASE; BREAST-CANCER; DIABETIC-PATIENTS; MONOAMINE TRANSPORTER; CHROMAFFIN GRANULES; RESERPINE BINDING; MITOCHONDRIAL-DNA; RESPIRATORY-CHAIN; CLINICAL-TRIALS; GAMMA-ENOLASE;

D O I：

10.1126/sciadv.1601756

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We report that the anticancer activity of the widely used diabetic drug metformin is strongly potentiated by syrosingopine. Synthetic lethality elicited by combining the two drugs is synergistic and specific to transformed cells. This effect is unrelated to syrosingopine's known role as an inhibitor of the vesicular monoamine transporters. Syrosingopine binds to the glycolytic enzyme alpha-enolase in vitro, and the expression of the gamma-enolase isoform correlates with nonresponsiveness to the drug combination. Syrosingopine sensitized cancer cells to metformin and its more potent derivative phenformin far below the individual toxic threshold of each compound. Thus, combining syrosingopine and codrugs is a promising therapeutic strategy for clinical application for the treatment of cancer.

引用

页数：12

共 62 条

[1] Metformin decelerates aging and development of mammary tumors in HER-2/neu transgenic mice [J].