Additive inhibitory effects of simvastatin and enzalutamide ...

[pjoshea13]

New cell study from Finland.

"Combination of simvastatin and enzalutamide {Xtandi} exerted additive growth inhibition in both cell lines"

-Patrick

ncbi.nlm.nih.gov/pubmed/278...

Biochem Biophys Res Commun. 2016 Nov 8. pii: S0006-291X(16)31876-9. doi: 10.1016/j.bbrc.2016.11.021. [Epub ahead of print]

Additive inhibitory effects of simvastatin and enzalutamide on androgen-sensitive LNCaP and VCaP prostate cancer cells.

Syvälä H1, Pennanen P2, Bläuer M3, Tammela TL4, Murtola TJ4.

Author information

1University of Tampere, School of Medicine, Department of Anatomy, Tampere, Finland.

2University of Tampere, School of Medicine, Tampere, Finland. Electronic address: [e-mail].

3Tampere University Hospital, Department of Gastroenterology and Alimentary Tract Surgery and Tampere Pancreas Laboratory, Tampere, Finland.

4University of Tampere, School of Medicine, Tampere, Finland; Tampere University Hospital, Department of Urology, Tampere, Finland.

Abstract

We evaluated the effects of simvastatin and antiandrogen enzalutamide on growth and androgen signaling in androgen-sensitive LNCaP and VCaP prostate cancer cells. Simvastatin alone abolished androgen-induced growth in both cell lines but decreased androgen receptor (AR) and prostate-specific antigen protein expression only in LNCaP, indicating that statin-induced growth inhibition is beyond AR transcriptional activity in VCaP. Combination of simvastatin and enzalutamide exerted additive growth inhibition in both cell lines accompanied with strong induction of autophagy in LNCaP. The data provide new insight into statins' effects on androgen signaling and their proposed role in enhancing androgen deprivation therapy in prostate cancer.

Copyright © 2016 Elsevier Inc. All rights reserved.

KEYWORDS:

Antiandrogen; Prostate cancer; Statin

PMID: 27833018 DOI: 10.1016/j.bbrc.2016.11.021

[PubMed - as supplied by publisher]

[pjoshea13]

Nala,

I wanted the max when I asked for Simvastatin ~7 years ago. My GP could only give me the 40 mg dose, since the FDA had stopped the use of the 80 mg dose - except for those already using it.

I had some muscle pain at first, but CoQ10 helped. Seemed to be a transition problem.

I was swayed by Dr. Myers discusion on Livalo to switch (4 mg) 6 months ago. Unlike other statins, it lowers blood sugar - the others raise it. Also, it may increase adiponectin levels - which might be a big plus.

Insurance company fought the prescription for 2 months. It's expensive.

-Patrick

[Hidden]

I can't tolerate simvastatin. I have GERD / reflux and take omeprazole. With simvastatin I get horrible heartburn even with the omeprazole. I am good to go with atorvastatin. I wonder if it has a benefit similar to simvastatin?

[pjoshea13 in reply to Hidden]

I will be doing a statin post, but I can tell you it is better to be lipophilic with PCa:

"Atorvastatin, lovastatin, and simvastatin are lipophilic, whereas pravastatin, rosuvastatin, and fluvastatin are more hydrophilic."

-Patrick

[patandemma in reply to pjoshea13]

patandemma@+pjoshea13

1.) "I will be doing a statin post, but I can tell you it is better to be lipophilic with PCa:"

Could you give me a preview of why lipophilic better than water soluble w/r PCa?

2.) "I was swayed by Dr. Myers discusion on Livalo to switch (4 mg) 6 months ago.

Was this due to side effects of your LIPID SOLUBLE simvastatin or because of glucose lowering and adiponectin benefits-since Livalo (pitavastatin) is WATER SOLUBLE?

sciencedaily.com/releases/2...

"We're excited about these findings," said Dr. Muhlestein. "If patients are having a hard time taking older statins, they should try this newer option. We believe the side effects of this drug differ from other statins because pitavastatin is water-soluble and metabolizes differently."

My inTernist suggested a water soluble statin because it might be less likely to cause cognitive changes since lesslikely to cross blood brain barrier than a lipophilic compound

[pjoshea13 in reply to patandemma]

1) - see my "Non-PCa Prescription Drugs: Statins - Lipophilic or Hydrophilic?" post of yesterday.

2) - here is the Myers / Livalo vblog post:

askdrmyers.wordpress.com/20...

I would switch back to Simvastatin, probably, if/when I end up on Lupron-Zytega.

-Patrick