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: Natural product-derived therapy for Metastatic human tumors: α-Solanine, found in bittersweet nightshade, and tomato among others, 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 up regulation 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 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 tumor growth.
From research findings to therapeutic opportunity :
This study suggests a natural product-derived anticancer therapy. α-Solanine is known to function as an anticancer agent (fig. 1). However, the mechanism of action is far from clear.
α-Solanine, 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).
Thus, pharmacological formulations encompassing “α-Solanine or its analogues or α-Solanine in combination with other known anticancer drugs” (fig. 1) may be used to inhibit metastatic progression of primary cancers.
Details of the Research findings:
Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.
Undisclosed mechanistic information: How does α-Solanine decrease the expression of c-Src and HK1/2 to inhibit tumor growth?
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Citation: Boominathan, L., Natural product-derived therapy for Metastatic human tumors: α-Solanine, found in bittersweet nightshade, and tomato among others, 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 up regulation of its target gene, 27/January/2017, 11.28 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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