Pentamidine. Another candidate for repurposing?

[pjoshea13]

New cell/mouse study below. [1]

"Pentamidine is an antimicrobial medication used to treat African trypanosomiasis, leishmaniasis, babesiosis, and to prevent and treat pneumocystis pneumonia (PCP) in people with poor immune function." [2]

"Pentamidine exerted profound inhibitory effects on proliferation, colony formation, migration and invasion of prostate cancer cells. In addition, the drug suppressed growth of xenograft tumours without exhibiting any obvious toxicity in nude mice." [1]

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/317...

Cell Prolif. 2019 Nov 13:e12718. doi: 10.1111/cpr.12718. [Epub ahead of print]

Pentamidine inhibits prostate cancer progression via selectively inducing mitochondrial DNA depletion and dysfunction.

Liu L1, Wang F1, Tong Y1, Li LF1, Liu Y1, Gao WQ1,2.

Author information

1

State Key Laboratory of Oncogenes and Related Genes, Renji-Med-X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

2

School of Biomedical Engineering & Med-X Research Institute, Shanghai Jiao Tong University, Shanghai, China.

Abstract

OBJECTIVES:

We investigated the anti-cancer activity of pentamidine, an anti-protozoal cationic aromatic diamidine drug, in prostate cancer cells and aimed to provide valuable insights for improving the efficacy of prostate cancer treatment.

MATERIALS AND METHODS:

Prostate cancer cell lines and epithelial RWPE-1 cells were used in the study. Cell viability, wound-healing, transwell and apoptosis assays were examined to evaluate the influences of pentamidine in vitro. RNA-seq and qPCR were performed to analyse changes in gene transcription levels upon pentamidine treatment. Mitochondrial changes were assessed by measuring mitochondrial DNA content, morphology, membrane potential, cellular glucose uptake, ATP production and ROS generation. Nude mouse xenograft models were used to test anti-tumour effects of pentamidine in vivo.

RESULTS:

Pentamidine exerted profound inhibitory effects on proliferation, colony formation, migration and invasion of prostate cancer cells. In addition, the drug suppressed growth of xenograft tumours without exhibiting any obvious toxicity in nude mice. Mechanistically, pentamidine caused mitochondrial DNA content reduction and induced mitochondrial morphological changes, mitochondrial membrane potential dissipation, ATP level reduction, ROS production elevation and apoptosis in prostate cancer cells.

CONCLUSIONS:

Pentamidine can efficiently suppress prostate cancer progression and may serve as a novel mitochondria-targeted therapeutic agent for prostate cancer.

© 2019 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.

KEYWORDS:

Pentamidine; mitochondria; mitochondrial DNA; prostate cancer

PMID: 31721355 DOI: 10.1111/cpr.12718

[2] en.wikipedia.org/wiki/Penta...

[Hidden]

What do you think of it? Looks like Dukoral and Pentamidine might have some common mechanisms. True?

My PSA is zero and I'm NED but this looks like it might be a good "preventative". Do you think so? (I'm planning on getting dukoral next weekend in Canada)

[pjoshea13 in reply to Hidden]

I have no opinion at this point. But It's worth having this sort of info in one's back pocket IMO.

-Patrick

[Schwah]

I’m confused. I’ve never seen a fully dressed mouse (other than Micky and Minnie and Mighty) so why do they have to get these mice nude? Lol

Schwah

[GP24 in reply to Schwah]

LOL. You can test human prostate cancer cells in nude mice only. They cannot reject xenografts.

en.wikipedia.org/wiki/Nude_...

[j-o-h-n in reply to Schwah]

It's a trap....

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 11/16/2019 10:57 PM EST

[donits]

Thank you for this info, new hope for us...

[TFBUNDY]

Good find Patrick but I see that it is administered by deep muscular injection so I guess badly absorbed. Can't see it immediately on the Indian pharmacy sites. Cheers

[PhilipSZacarias]

Excellent! Another drug for the armamentarium against PCa. Cheers, Phil

[MateoBeach]

The mechanism would not be the same as dukoral. Since dukoral is a vaccine (stimulating an immune response) and pentamidine is an anti-parasitic (analogous to an antibacterial). Personally I would look for at least some human trial, even a pilot Phase I study, before advocating. Great to have new promising possibilities in the pipeline.