Combinatorial therapy for Metastatic human tumors:  A pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263 (MAN)  decreases the expression of c-Src protein, inhibits the expression of a number of enzymes in glycolytic cycle, and suppresses proliferation, migration, invasion, tumorigenesis and metastasis via upregulation of its target gene, 11/February/2017, 12.34 am

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Introduction: What they say:

A study from the State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102, China shows that “c-Src phosphorylation and activation of hexokinase promotes tumorigenesis and metastasis.” This study was published in the 5 January 2017 issue of the journal “Nature communications”

by Prof. Li Qinxi, Jia Zhang, and others.


What we say:

On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that:  Combinatorial therapy for Metastatic human tumors:  A pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263 (MAN)  decreases the expression of c-Src protein, inhibits the expression of a number of enzymes in glycolytic cycle, and suppresses proliferation, migration, invasion, tumorigenesis and metastasis via upregulation of its target gene


From Significance of the study to Public health relevance:

Given that: (i) each year nearly 14 million people globally are diagnosed with cancer, and a little more than half of them will die; (ii) cancer deaths globally are expected to be doubled by 2030; (iii) cancer treatment causes the highest economic loss compared to all the known causes of death worldwide, there is an urgent need to find: (i) a way to prevent an individual from being susceptible to cancer by strengthening his/her own immune system; (ii) a cheaper alternative to the existing expensive anticancer drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and prevent metastatic progression and relapse of cancers.


What we infer from what they say:

Prof. Li Qinsi’s research team has recently shown that oncoprotein c-Src: (1) phosphorylates the rate-limiting enzyme of the glycolysis Hexokinase-1/2 (HK1)/(HK2) at Tyr732; (2) prevents HK dimer formation; (3) increases affinity (decreases Km value for glucose) for glucose; and (4) promotes tumor survival even under poor glucose conditions. Further, they have shown that HK1-Y732 phosphorylation level correlates with metastasis capability of primary cancers. Together, these findings suggest that inhibition of c-Src and its downstream target Hexokinase expression in cancer cells may prevent tumour growth.


From research findings to therapeutic opportunity :

This study suggests combinatorial therapy for metastatic cancers. A pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263, by increasing the expression of its target genes, it may decrease the expression of c-Src and HK-1/2 (fig. 1). Thereby, it may: (i) augment HK dimer formation; (ii) increase Km value for glucose; (iii) decrease tumor survival; (iv) inhibit tumor proliferation and growth; and (v) promote tumor regression (fig.1).

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Thus, pharmacological formulations encompassing Metformin and Navitoclax/ABT-263 or its anologs, either alone or in combination with other known anticancer drugs,” (fig. 1) may be used to inhibit metastatic progression of primary cancers.

Figure 1. Mechanistic insights into how a pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263 (MAN) functions as an anticancer agent. MAN, by increasing the expression of its target genes, it may suppress the expression of c-Src and Hexokinase- 1/2 to promote tumour regression

Figure 2. A pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263 (MAN) functions as a potent anti-cancer/metastasis agent.

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Details of the Research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Amount: $100#

Undisclosed mechanistic information: How does a pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263 (MAN) decrease the expression of c-Src and HK1/2?

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References:

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Citation: Boominathan, L., Combinatorial therapy for Metastatic human tumors:  A pharmaceutical mixture encompassing metformin and Navitoclax/ABT-263 (MAN)  decreases the expression of c-Src protein, inhibits the expression of a number of enzymes in glycolytic cycle, and suppresses proliferation, migration, invasion, tumorigenesis and metastasis via upregulation of its target gene, 11/February/2017, 12.34 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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