From Significance of the study to Public health relevance:
Given that: (1) Cancer suppressor p53 is mutated in more than 50% of human cancers of different tissue origin; (2) p53 pathway is altered in about 80% of tumors.; (3) our understanding is incomplete in terms of molecular targets and the oncogenic/malignant pathways involved in mutant p53-overexpressing tumors; (4) cancer causes the highest economic loss compared to all the known causes of death worldwide; and (5) cancer causes the considerable economic loss worldwide, 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 mutant p53-overexpressing human cancers.
From therapeutic strategy to Research Findings:
(i) Therapeutic strategy:
This study suggests a therapeutic strategy for stalling the progression of p53-deficient/deleted or mutant-p53 expressing metastatic cancers. By activating tumor suppressor p53’s unmutated “homologous protein such as TAp73/p63” in p53-deficient or mutant-p53 expressing metastatic cancer cells, one can stall their progression.
(ii) Research findings:
Kuwanon V, by increasing the expression of its target genes, it may not only increase the expression of tumor suppressors genes, such as TAp73, TAp63, PTEN, etc., but also increase a number of metastatic suppressor genes, such as TPM1, TIMP3, BTG2, PDCD4, SPRY1/2, CCM1/KRIT1 etc. Thereby, it may inhibit the migration and invasion of metastatic cancer cells expressing mutant-p53 (figure1).
Given the ability of Kuwanon V to induce the expression of TAp73, TAp63, PTEN, TPM1, TIMP3, BTG2, PDCD4, SPRY1/2, CCM1/KRIT1, long ncRNA Gas5 in p53-mutated human tumors, pharmacological formulations encompassing “Kuwanon V or its analogues or Kuwanon V in combination with any of the known anticancer agents” may be used to inhibit the progression of p53-mutated invasive metastatic tumors.
Together, this study suggests a natural-product-based therapy for p53-mutated metastatic human tumors.[easy_payment currency=”USD”]
Details of the research findings:
Idea Proposed/Formulated by: Dr L Boominathan Ph.D.
Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/
Undisclosed mechanistic information: How Kuwanon V increases the expression of tumor suppressor genes (TAp73, TAp63, and PTEN); and metastatic suppressor genes (TPM1, TIMP3, BTG2, PDCD4, SPRY1/2 and CCM1/KRIT1) in mutant p53 expressing cancer cells?
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Citation: Boominathan, L., Therapeutic insights into “awakening the sleeping/cancer-protecting angels” in mutant p53-expressing human tumors: Kuwanon V, one of the constituents of Mulberry, increases the expression of tumor suppressor p53 homologue TA-p73/p63, PTEN, TPM1, TIMP3, BTG2, PDCD4, SPRY1/2 and CCM1/KRIT1 and induces regression of p53-mutated human tumors via down regulation of its target gene, 13/December/2016, 11.35 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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