Therapeutic insights into “awakening the sleeping/cancer-protecting angels” in mutant p53-expressing human tumors: Pioglitazone (trade name: Actos), an antihyperglycemic drug, 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, 2/January/2017, 8.26 am

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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:  

A number of studies suggests that the antidiabetic drug Pioglitazone, one of the ten best selling drugs in the US whose sales had exceeded $2.4 billion in 2008, functions also as an anticancer agent. However, the mechanism of action is far from clear. This study suggests that Pioglitazone, by increasing the expression of its target gene, it may not only increase the expression of tumor suppressors genes, such as TAp73, TAp63, PTEN, INK4a etc., but also increase a number of metastatic suppressor genes, such as TPM1, TIMP3, BTG2, PDCD4, SPRY1/2, CCM1/KRIT1, E-Cadherin, BRMS1, MTSS1 etc. Thereby, it may inhibit the migration and invasion of metastatic cancer cells expressing mutant-p53 (figure1).

pioglitazone-induces-tap73-tap63-and-other-tumor-suppressors

Figure 1. Mechanistic insight into how Pioglitazone functions as an anticancer/antimetastatic agent.  Pioglitazone/Actos, by activating tumor suppressor genes, such as TAp73, TAp63, PTEN, PDCD4, BTG2, E-Cadherin 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 Pioglitazone 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 Pioglitazone or its analogues or Pioglitazone plus any of the known anticancer agents” may be used to inhibit the progression of p53-mutated invasive metastatic tumors.

price-100

Together, this study provides, for the first time, a detailed mechanistic insight into how the antidiabetic drug Pioglitazone may function as an anticancer/antimetastatic agent.

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Details of the research findings

Idea Proposed/Formulated by: Dr L Boominathan Ph.D.

Terms & Conditions apply http://genomediscovery.org/registration/terms-and-conditions/

Amount: $100#

Undisclosed mechanistic information: How Pioglitazone 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?

For purchase and payment details, you may reach us at admin@genomediscovery.org

#Research cooperation


References:

Web: http://genomediscovery.org or http://newbioideas.com

Citation: Boominathan, L., Therapeutic insights into “awakening the sleeping/cancer-protecting angels” in mutant p53-expressing human tumors: Pioglitazone (trade name: Actos), an antihyperglycemic drug, 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, 2/January/2017, 8.26 am, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org

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