Ranolazine (used for angina) could po... - Advanced Prostate...

Advanced Prostate Cancer

22,379 members28,143 posts

Ranolazine (used for angina) could potentially be repurposed for PCa. Only mouse studies so far.

Graham49 profile image
7 Replies

“Treatment of cancer patients with lipid metabolic inhibitors like ranolazine could potentially re-activate the immune cells to restore and enhance cellular-mediated antitumor immunity and tumor regression.”

Targeting Fat Oxidation in Mouse Prostate Cancer Decreases Tumor Growth and Stimulates Anti-Cancer Immunity

by Amanda Guth 1, Emily Monk 2ORCID, Rajesh Agarwal 3, Bryan C. Bergman 4, Karin A. Zemski-Berry 4, Angela Minic 5ORCID, Kimberly Jordan 5 and Isabel R. Schlaepfer 2,*ORCID 1

Department of Clinical Sciences, Flint Animal Cancer Center, Colorado State University, Fort Collins, CO 80523, USA 2

Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA 3

School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA 4

Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA 5

Department of Immunology and Microbiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA

Int. J. Mol. Sci. 2020, 21(24), 9660; doi.org/10.3390/ijms21249660

Submission received: 19 November 2020 / Revised: 12 December 2020 / Accepted: 15 December 2020 / Published: 18 December 2020

Abstract

Lipid catabolism represents an Achilles heel in prostate cancer (PCa) that can be exploited for therapy. CPT1A regulates the entry of fatty acids into the mitochondria for beta-oxidation and its inhibition has been shown to decrease PCa growth. In this study, we examined the pharmacological blockade of lipid oxidation with ranolazine in TRAMPC1 PCa models. Oral administration of ranolazine (100 mg/Kg for 21 days) resulted in decreased tumor CD8+ T-cells Tim3 content, increased macrophages, and decreased blood myeloid immunosuppressive monocytes. Using multispectral staining, drug treatments increased infiltration of CD8+ T-cells and dendritic cells compared to vehicle. Functional studies with spleen cells of drug-treated tumors co-cultured with TRAMPC1 cells showed increased ex vivo T-cell cytotoxic activity, suggesting an anti-tumoral response. Lastly, a decrease in CD4+ and CD8+ T-cells expressing PD1 was observed when exhausted spleen cells were incubated with TRAMPC1 Cpt1a-KD compared to the control cells. These data indicated that genetically blocking the ability of the tumor cells to oxidize lipid can change the activation status of the neighboring T-cells. This study provides new knowledge of the role of lipid catabolism in the intercommunication of tumor and immune cells, which can be extrapolated to other cancers with high CPT1A expression.

Keywords: CPT1A; prostate cancer; acyl-carnitines; ranolazine; CD8 T-cells; dendritic cells; lipid metabolism

Written by
Graham49 profile image
Graham49
To view profiles and participate in discussions please or .
Read more about...
7 Replies
Graham49 profile image
Graham49

Here’s another paper with some epidemiological human evidence.

“A key question was whether the life expectancy of cancer patients taking ranolazine for non-cancer indications (e.g., angina pectoris) would differ from that of patients not using ranolazine. Data from breast, colon and prostate cancers over a 10-year period were pooled. Of these ca. 54,000 patients, a subgroup of 165 individuals were found to have taken ranolazine at various stages of their cancer. Prescriptions had started either before diagnosis and extended afterwards or started on average 4 years post-diagnosis. This group was compared with patients who did not take ranolazine. For the study group taking ranolazine (in the concentration range used for treating angina pectoris), the hazard ratio was ca. 0.41 (i.e., risk of dying from cancer was reduced by 59%) and this effect was a highly significant (p < 0.001). For those patients who started taking ranolazine after diagnosis, the hazard ratio was slightly higher (0.54) but the beneficial effect was still significant (p < 0.01).”

Ranolazine: a potential anti-metastatic drug targeting voltage-gated sodium channels

Mustafa B. A. Djamgoz

British Journal of Cancer (2024)Cite this article

Abstract

Background

Multi-faceted evidence from a range of cancers suggests strongly that de novo expression of voltage-gated sodium channels (VGSCs) plays a significant role in driving cancer cell invasiveness. Under hypoxic conditions, common to growing tumours, VGSCs develop a persistent current (INaP) which can be blocked selectively by ranolazine.

Methods

Several different carcinomas were examined. We used data from a range of experimental approaches relating to cellular invasiveness and metastasis. These were supplemented by survival data mined from cancer patients.

Results

In vitro, ranolazine inhibited invasiveness of cancer cells especially under hypoxia. In vivo, ranolazine suppressed the metastatic abilities of breast and prostate cancers and melanoma. These data were supported by a major retrospective epidemiological study on breast, colon and prostate cancer patients. This showed that risk of dying from cancer was reduced by ca.60% among those taking ranolazine, even if this started 4 years after the diagnosis. Ranolazine was also shown to reduce the adverse effects of chemotherapy on heart and brain. Furthermore, its anti-cancer effectiveness could be boosted by co-administration with other drugs.

Conclusions

Ranolazine, alone or in combination with appropriate therapies, could be reformulated as a safe anti-metastatic drug offering many potential advantages over current systemic treatment modalities.

DrawingSnowmen profile image
DrawingSnowmen in reply toGraham49

Fascinating. Here's the link: nature.com/articles/s41416-...

Heilung18-Gesund profile image
Heilung18-Gesund in reply toDrawingSnowmen

Thank you, excellent.

Islandboy2021 profile image
Islandboy2021 in reply toGraham49

Is there anyone on this site that has used this drug for prostate cancer. What would the daily dose be like and can you take it along with SOC drugs.

Thanks

Islandboy2021 profile image
Islandboy2021 in reply toGraham49

This looks like another great alternative therapy. The problem with all these alternative therapies is trying to get a doctor to prescribe these drugs. I am constantly suggesting possible drugs that could have a benefit and the doctors do not respond. All the doctors that I have been working with will not prescribe these drugs. The question is how do you access these drugs?

Graham49 profile image
Graham49 in reply toIslandboy2021

There is a list of integrative doctors on howtostarvecancer.com that might help.

j-o-h-n profile image
j-o-h-n

Mice have all the fun.......

Good Luck, Good Health and Good Humor.

j-o-h-n

Not what you're looking for?

You may also like...

Metformin inhibits SUV39H1-mediated PCa migration

New study below. They keep finding new anti-PCa mechanisms for Metformin. Note: SUV39H1 is a...
pjoshea13 profile image

Proton Pump Inhibitors and Prostate Cancer-Specific Mortality

A new mostly-Canadian study below [1]. "We identified 21,512 men aged ≥ 66, with a history of a...
pjoshea13 profile image

Testosterone inhibits the growth of PCa (in mice).

New study below. The BAT concept is that supraphisiological testosterone [T] is required for...
pjoshea13 profile image

Effectiveness of Radical Prostatectomy Versus External Beam Radiation Therapy Plus Brachytherapy in Patients with High-risk Localized PCa.

New study below. When I opted for Radical Prostatectomy [RP] 14 years ago it was on the basis of...
pjoshea13 profile image

Adrenal androgens rescue prostatic dihydrotestosterone production and growth of prostate cancer cells after castration.

New study below [1] which sheds light on the role of adrenal hormones in PCa progression while on...
pjoshea13 profile image

Moderation team

Bethishere profile image
BethishereAdministrator
Number6 profile image
Number6Administrator
Darryl profile image
DarrylPartner

Content on HealthUnlocked does not replace the relationship between you and doctors or other healthcare professionals nor the advice you receive from them.

Never delay seeking advice or dialling emergency services because of something that you have read on HealthUnlocked.