Introduction: What they say
A study from the Zhongnan Hospital of Wuhan University, Wuhan 430071, China; and Medical Research Institute, Wuhan University, Wuhan 430071, China shows that “Polo-like Kinase-1 Regulates Myc Stabilization and Activates a Feedforward Circuit Promoting Tumor Cell Survival.” This research paper was published in the 3 November 2016 issue of the journal “Molecular cell” [One of the best research journals in General Biology with an I.F of 13.958] by Prof. Guoliang Qing, Dr. Daibiao Xiao, and others.
What we say:
On the foundation of this interesting finding, Dr L Boominathan PhD, Director-cum-chief Scientist of GBMD, reports that: Molecular therapy for N-Myc-overexpressing tumors: Cucurbitacin D, found in Trichosanthes kirilowii (Gualou), Phormium tenax, and Luffa amara among others, increases the levels of tumor suppressor proteins, TAp63, TAp63 and Fbw7 (SCF Fbw7 ubiquitin ligase), inhibits the expression of pro-survival proteins N-Myc, Cyclin-E and Mcl-1, and stalls the progression of N-Myc-overexpressing cancers via down regulation of its target gene
Significance of the study:
Given that: (1) N-Myc is amplified in neuroblastoma (20%), Alveolar rhabdomyosarcoma (25%), Small cell lung cancer (20%), & neuroendocrine prostate cancer (40%); (2) N-Myc is overexpressed in a number of cancers, including Alveolar rhabdomyosarcoma, breast cancer and prostate cancer; (3) even intense multimodal treatment saves only less than 50% of neuroblastoma patients; (4) our understanding is incomplete in terms of molecular targets and the oncogenic/malignant pathways involved in N-Myc amplified or overexpressed cancers; (5) cancer causes the highest economic loss compared to all the known causes of death worldwide; and (6) Myc-overexpressed cancer is a common occurance; and it results in considerable economic loss globally, there is an urgent need to find: (i) a cheaper alternative to the existing expensive drugs; (ii) a side-effect-free natural product-based drug; and (iii) a way to effectively treat and stall metastatic progression and relapse of Myc-amplified/overexpressed human cancers.
What is known?
A number of studies suggest that N-Myc is amplified and overexpressed in cancers, as indicated above. However, the mechanistic basis of its deregulation remains largely unclear.
Prof. Qing’s research team has recently shown that: (1) PLK-1 promotes degradation of tumor suppressor protein Fbw7, and thereby, prevents degradation of its substrates such as N-Myc, N-cym, Cyclin-E and Mcl-1; and (2) N-Myc, in turn, in a positive feedback loop, increases the expression of PLK-1. Further, they showed that inhibition of PLK-1 in N-Myc-overexpressing tumors, either alone or together with Bcl-2 antagonists, not only regressed, but also stalled the progression of tumors, possibly, via induction of tumor suppressor Fbw7.
What we say: Research findings:
This study suggests a Natural product-based therapy for Myc-overexpressing cancers.
[easy_payment currency=”USD”]This study suggests, for the first time, a natural product based therapy for N-Myc-overexpressing tumors. Cucurbitacin D, by increasing the expression of its target gene, it may decrease the expression of N-Myc. Thereby, it may: (1) inhibit oncoproteins PLK-1, Cyclin-E, Mcl-1, Bcl-2 and N-cym expression; (2) increase tumor suppressors Fbw7, TAp73, and TAp63 levels; and (3) inhibit the progression of N-Myc-overexpressing cancers.
Thus, pharmacological formulations encompassing “Cucurbitacin D or its analogs or Cucurbitacin D in combination with other anticancer agents“ may be used to treat N-Myc-overexpressing tumors such as Neuroblastoma and Small cell lung cancer.
Details of the research findings:
Idea Proposed/Formulated (with experimental evidence) by:
Dr L Boominathan Ph.D.
Undisclosed information: How Cucurbitacin D increases the expression of tumor suppressors TAp63, TAp63 and Fbw7, while inhibiting the expression of Oncoproteins N-Myc, N-cym, Cyclin-E, Mcl-1 and Bcl-2
# Research cooperation
Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/
Citation: Boominathan, L., Molecular therapy for N-Myc-overexpressing tumors: Cucurbitacin D, found in Trichosanthes kirilowii (Gualou), Phormium tenax, and Luffa amara among others, increases the levels of tumor suppressor proteins, TAp63, TAp63 and Fbw7 (SCF Fbw7 ubiquitin ligase), inhibits the expression of pro-survival proteins N-Myc, Cyclin-E and Mcl-1, and stalls the progression of N-Myc-overexpressing cancers via down regulation of its target gene, 4/February/2017, 11.25 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
# Research cooperation