Therapeutic insights into “awakening the sleeping/cancer-protecting angels” in mutant p53-expressing human tumors: Cancer Suppressor BMP4 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, 24/December/2016, 9.36 pm
Natural product-derived therapy for enhancing anti-cancer immunity: Berberine, found in Berberis, decreases the level of LATS1/2 (large tumor suppressor 1 and 2), increases immunogenicity of tumors, enhances anti-tumor immune responses, and inhibits tumor growth via down regulation of its target gene, 23/December/2016, 10.16 pm
December 23, 2016Natural product-derived PD-L1 pathway blockade enhances the efficacy of Cancer immunotherapy: γ-Bisabolene, one of the components in Cardamom, Cubeb, lemon, and Oregano among others, inhibits the expression of PD-L1, inhibits inflammatory signalling and the number of tumor-infiltrating lymphocytes and macrophages, increases Cytotoxic activity of T-cells, decreases tumor burden and increases survival via up-regulation of its target gene, 24/December/2016, 10.45 pm
December 24, 2016From 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:
Cancer suppressor BMP4, by decreasing 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).
Figure 1. Mechanistic insight into how BMP4 functions as an anticancer agent. BMP4, by activating tumor suppressor genes, such as TAp73, TAp63, PTEN, PDCD4, BTG2, etc., and metastatic suppressor genes, such as TPM1, TIMP3, SPRY1/2 etc., in metastatic tumors, it may inhibit the progression of mutant-p53 expressing human cancers.
Therapeutic opportunity:
Given the ability of BMP4 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 “BMP4 activators or BMP4 activators plus 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.
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Undisclosed mechanistic information: How BMP4 increases the expression of tumor suppressor genes (TAp73, TAp63, and PTEN); and metastatic suppressor genes (TPM1, TIMP3, BTG2, PDCD4, SPRY1/2, CCM1/KRIT1, RECK) in mutant p53 expressing cancer cells?
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References:
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Citation: Boominathan, L., Therapeutic insights into “awakening the sleeping/cancer-protecting angels” in mutant p53-expressing human tumors: Cancer Suppressor BMP4 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, 24/December/2016, 9.36 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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