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Polyphenol based drug to block Prostate Cancer Senescence

Graham49 profile image
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Cross-Linked Polyphenol-Based Drug Nano-Self-Assemblies Engineered to Blockade Prostate Cancer Senescence

Prashanth K.B. Nagesh, Pallabita Chowdhury, Elham Hatami, Sonam Kumari, Vivek Kumar Kashyap, Manish K. Tripathi, Santosh Wagh, Bernd Meibohm, Subhash C. Chauhan, Meena Jaggi, and Murali M. Yallapu*

Cite this: ACS Appl. Mater. Interfaces 2019, 11, 42, 38537–38554

Publication Date:September 25, 2019

doi.org/10.1021/acsami.9b14738

Copyright © 2019 American Chemical Society

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SUBJECTS:Cancer,Nanoparticles,Rodent models,Cells,Tumors

Abstract

Abstract Image

Cellular senescence is one of the prevailing issues in cancer therapeutics that promotes cancer relapse, chemoresistance, and recurrence. Patients undergoing persistent chemotherapy often develop drug-induced senescence. Docetaxel, an FDA-approved treatment for prostate cancer, is known to induce cellular senescence which often limits the overall survival of patients. Strategic therapies that counter the cellular and drug-induced senescence are an unmet clinical need. Towards this an effort was made to develop a novel therapeutic strategy that targets and removes senescent cells from the tumors, we developed a nanoformulation of tannic acid–docetaxel self-assemblies (DSAs). The construction of DSAs was confirmed through particle size measurements, spectroscopy, thermal, and biocompatibility studies. This formulation exhibited enhanced in vitro therapeutic activity in various biological functional assays with respect to native docetaxel treatments. Microarray and immunoblot analysis results demonstrated that DSAs exposure selectively deregulated senescence associated TGFβR1/FOXO1/p21 signaling. Decrease in β-galactosidase staining further suggested reversion of drug-induced senescence after DSAs exposure. Additionally, DSAs induced profound cell death by activation of apoptotic signaling through bypassing senescence. Furthermore, in vivo and ex vivo imaging analysis demonstrated the tumor targeting behavior of DSAs in mice bearing PC-3 xenograft tumors. The antisenescence and anticancer activity of DSAs was further shown in vivo by inhibiting TGFβR1 proteins and regressing tumor growth through apoptotic induction in the PC-3 xenograft mouse model. Overall, DSAs exhibited such advanced features due to a natural compound in the formulation as a matrix/binder for docetaxel. Overall, DSAs showed superior tumor targeting and improved cellular internalization, promoting docetaxel efficacy. These findings may have great implications in prostate cancer therapy.

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RonnyBaby profile image
RonnyBaby

'Headsy' stuff - but interesting and encouraging anytime you read about advances and new approaches to an old known problem .....

Karmaji profile image
Karmaji in reply toRonnyBaby

it is an important directionBut not many talk of senelogy

Life Extension guys have capsules senolytic activator..

Seems positive with no side effect

Hope some folks talk of their knowledge about

getting rid of senesence cancer cells

One tries these supplements but how to know their usefullness

Enjoy the show

in reply toKarmaji

I believe the 72 hour water fasts can clean up senesence cells, I just don't know if senesence cancer cells are also cleaned up.

Once I'm done my 2 yrs of adt +zytiga I'm planning on adding a quarterly 72 hour water fast to my regiment.

Loves2golf profile image
Loves2golf in reply toKarmaji

Any thoughts on finestin?

RonnyBaby profile image
RonnyBaby in reply toKarmaji

I'm ordering it from Amazon - I've been taking supplements to ADD to the fight vs. PCa and the results are a work in progress - a clinical trial of one - but I'm responding well overall and optimistic about being around awhile longer to keep up the fight.

My original post was 11 months ago - interesting that you are 'looking' at the archives.

Thanks for sharing .....

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