Anti-Androgen Abiraterone Acetate Improves the Therapeutic Efficacy of Statins on Castration-Resistant Prostate Cancer Cells.

[pjoshea13]

New cell study [1] below.

I have used Simvastatin for many years to try to prevent the production of cholesterol in PCa cells, & to otherwise limit access to circulating cholesterol. There appears to be synergy between statins & Zytiga (Abiraterone):

"We determined that androgen biosynthesis inhibitors simvastatin, atorvastatin, and ketoconazole directly inhibit growth, migration, and colony formation of LNCaP C-81 cells, which exhibit de novo androgen biosynthesis, with simvastatin being the most effective. Importantly, in combination treatments, statins specifically enhanced growth suppression with added effects by anti-androgen abiraterone acetate on the CR PCa cells. Thus, statins can be used in conjunction with abiraterone acetate to enhance anti-androgen therapy for CR PCa."

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/313...

J Oncol Res Ther. 2017;3(5). pii: 139. Epub 2017 Dec 20.

Anti-Androgen Abiraterone Acetate Improves the Therapeutic Efficacy of Statins on Castration-Resistant Prostate Cancer Cells.

Miller DR1, Ingersoll MA1, Chou YW1,2, Wakefield CB1,3, Tu Y4, Lin FF1,5, Chaney WG1, Lin MF1,3,6,7.

Author information

1

Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, USA.

2

BioBank/Tissue Bank, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, China.

3

Section of Urological Surgery, School of Medicine, University of Nebraska Medical Center, Omaha, NE, USA.

4

Department of Pharmacology, Creighton University School of Medicine, Omaha, NE, USA.

5

Human Genetic Laboratory, Munroe-Meyer Institute, University of Nebraska Medical Center, Omaha, NE, USA.

6

Eppley Institute for Cancer Research, University of Nebraska, Medical Center, Omaha, NE, USA.

7

College of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan, China.

Abstract

The treatment of castration-resistant (CR) prostate cancer (PCa) is limited. A sub-population of CR PCa tumors can synthesize androgens for intracrine androgen receptor (AR) activation, thus targeting androgen biosynthesis could be an effective therapeutic option for these patients. We determined that androgen biosynthesis inhibitors simvastatin, atorvastatin, and ketoconazole directly inhibit growth, migration, and colony formation of LNCaP C-81 cells, which exhibit de novo androgen biosynthesis, with simvastatin being the most effective. Importantly, in combination treatments, statins specifically enhanced growth suppression with added effects by anti-androgen abiraterone acetate on the CR PCa cells. Thus, statins can be used in conjunction with abiraterone acetate to enhance anti-androgen therapy for CR PCa.

KEYWORDS:

Anti-Androgens; Castration-Resistant Prostate Cancer; Combination Treatments; Prostate Cancer; Statins

PMID: 31328181

[timotur]

Thanks for posting this. I'm thinking of starting Simvastatin at the end of RT in a few weeks. I'll have 12 months left on ADT (Z + L), and this would hopefully lower the chance of progression/reoccurrence. Do you have any SE's on Simvastatin? Thx.

[pjoshea13 in reply to timotur]

None at all, in my case. -P.

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

I take 1 Simvastatin 10mg every night. Had some side effects with leg pain and dose cut to 5mg and now back on it at 10mg (been taking it since Dec. 2010).

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 07/26/2019 6:40 PM DST

[GeorgeGlass]

Would the maximum dose of zocor be more effective than the medium dose?

[pjoshea13 in reply to GeorgeGlass]

All of the studies which I have read that mention dosage, indicate that higher is always better.

-Patrick

[GeorgeGlass in reply to pjoshea13]

Any idea why they wouldn't include Crestor (Rosuvastatin) in their study? Are you taking 40mg of simvastatin? I read an article that says that a 40mg Zocor dose is the equivalent to 10mg Crestor in reducing LDL cholesterol, which may make my cardiologist balk at switching to zocor. I take 20 mg crestor and coincidentally, my nuclear stress test showed significant improvement from the past four years. No signs of Angina this time or abnormal downward blips on the heartbeat monitor. I suspect I would have gotten those if I had stayed on the treadmill longer than ~12 minutes of the "bruce" protocal.

[pjoshea13 in reply to GeorgeGlass]

"Any idea why they wouldn't include Crestor (Rosuvastatin) in their study?"

Possibly because:

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

google.com/search?source=hp...

-Patrick

[GeorgeGlass in reply to pjoshea13]

Ok, so the tissue absorbtion of lipophilic statins are more disruptive, in the time metastasis process, than the hydrophilic statins. Good to know.