Digitoxin

[pjoshea13]

New study below [1].

The foxglove-related arrhythmia drugs (Digitoxin, Digoxin, Digitalis) don't crop up much in the PCa literature, although there was a post last year on: "Sotalol & Digoxin (antiarrhythmic drugs) & PCa." [2].

For Digitoxin, aside from the 1979 paper "A therapeutic castastrophe, entailing 16 exhumations, following the administration of digitoxin instead of oestradiol benzoate to prostatic cancer patients: identification of the poison." (Oops!), there isn't much of interest.

***

The taxanes, including Taxotere (Docetaxel) inhibit microtubule formation. Paclitaxel was the first such taxane drug. From a 2002 paper [3]:

"In this study, we report for the first time that cardiac glycosides (e.g. ouabain and digitoxin) induced resistance of human prostate cancer cells (PC-3) in vitro to tubulin-binding anticancer drugs, such as paclitaxel, colchicine, vincristine and vinblastine."

***

"οἰκ" is Greek for "house" & Anoikis was coined for the process that deals with cells that have left home by breaking away from the extracellular matrix. Cancer cells have to circumvent Anoikis to become metastatic. From 2009 [4]:

"To identify novel anoikis sensitizers in anoikis-resistant PPC-1 prostate adenocarcinoma cells, a library of 2,000 off-patent drugs and natural products was screened ... This screen identified five members of the family of cardiac glycosides as anoikis sensitizers, including ouabain, peruvoside, digoxin, digitoxin, and strophanthidin."

***

The new study [1] reports that:

"Digitoxin Inhibits Epithelial-to-Mesenchymal-Transition in Hereditary Castration Resistant Prostate Cancer"

"We have previously reported that the cardenolide drug digitoxin blocks TNFα/NFκB-driven proinflammatory signaling."

"Castration Resistant Prostate Cancer (CRPC) is thought to be driven by a collaborative mechanism between TNFα/NFκB and TGFβ signaling, leading to inflammation, Epithelial-to-Mesenchymal-Transition (EMT), and metastasis."

"In vivo, in a syngeneic, immune competent rat model of metastatic CRPC, we show that digitoxin {suppresses expression of} genes classically driven by NFκB, and of multiple EMT genes associated with metastasis. Concurrently, digitoxin suppresses tumor growth and metastasis in these animals, and prolongs survival."

-Patrick

[1] Full Text: frontiersin.org/articles/10...

[2] healthunlocked.com/advanced....

[3] ncbi.nlm.nih.gov/pubmed/122...

[4] ncbi.nlm.nih.gov/pubmed/192...

[JuanVV]

Hi pjoshea13

Thanks for this info, got a bit lost with so much chemical teminology, does it mean that Digoxin and sotalol works favourably in surpressing tumours in PC with mets?

My husband takes sotalol for his arrhythmia and Xtandi,I understood the mix between ADT or other drugs and sotalol made the QTc increase?

[pjoshea13 in reply to JuanVV]

Since he is using Sotalol, I will refer to the PCa literature for that.

[1] (2015) [Finland / Johns Hopkins] "Our results suggest that use of digoxin or other antiarrhythmic agents in general does not affect prostate cancer risk at population level with maximum exposure time of eight years. However, sotalol use was inversely associated both with advanced prostate cancer risk, and long‐term users also had lower risk of overall prostate cancer. This drug deserves further study as prostate cancer preventive agent."

i.e. there is a suggestion of benefit for those with advance PCa. However, ...

[2] (2018) [Finland again] Long-term Sotalol use was not associated with survival.

-Patrick

[1] onlinelibrary.wiley.com/doi...

[2] ncbi.nlm.nih.gov/pmc/articl...

[JuanVV in reply to pjoshea13]

Thanks so much! I'll read links in depth, sounds quite controversial.

[pjoshea13]

"Where There's a Will, There's a War"