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 antidepressant Amitriptyline functions as an anticancer agent. However, the mechanism of action is far from clear.
This study suggests, for the first time, that amitriptyline (trade name: Elavil), by decreasing the expression of its target gene, it may increase the expression of tumor suppressors genes, such as TIMP3, CCM3/KRIT1, TAp76α, TPM1, TAp73α, and others. Thereby, it may inhibit the migration and invasion of metastatic cancer cells expressing mutant-p53 (figure1).
Given the ability of Amitriptyline to induce the expression of a number of tumor suppressor genes, pharmacological formulations encompassing “amitriptyline or its analogues, either alone or in combination with other anticancer drugs,“ may be used to inhibit the progression of p53-mutated invasive metastatic tumors.
Taken together, this study suggests that oncologists may consider treating terminally ill metastatic cancer patients with Amitriptyline, as it may stall the progression of advanced metastatic cancers.
Details of the research findings:
Idea Proposed/Formulated by: Dr L Boominathan Ph.D.
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Undisclosed mechanistic information: How amitriptyline increases the expression of tumor suppressor genes, such as TIMP3, CCM3/KRIT1, TAp73α, TPM1, TAp63α and others, 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: Amitriptyline (trade name: Elavil), a medication used to treat major depressive disorder, anxiety disorder, and bipolar disorder, increases the expression of tumor suppressors genes, such as TIMP3, CCM3/KRIT1, TA-p73/p63, TPM1, and others, induces regression of p53-mutated human tumors, via down regulation of its target gene, 22/April/2017, 11.24 pm, Genome-2-Bio-Medicine Discovery center (GBMD), http://genomediscovery.org
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