Spermidine/Spermine N1 -Acetyltransferase-1 as a Diagnostic Biomarker in Human Cancer

Abstract

Aim:SSAT-1 is an enzyme that plays a critical role in cell growth. Amantadine, a FDA-approved antiviral drug, is a substrate for SSAT-1. The utility of amantadine as an agent to demonstrate elevated SSAT-1 activity linked to cancer was conducted.Results:High levels of SSAT-1 expression were measured in tumor human cell lines, and in breast, prostate and lung tumor tissue. An increase in the urinary levels of acetylated amantadine in cancer patients was observed.Conclusion:Increases in SSAT-1 contents in tumor tissue could be of value in targeting cancers with high SSAT-1 expression for confirmation/quantification. The high levels of acetylated amantadine could be used as a simple and useful screening test for the presence of cancer.

Use of Amantadine as Substrate for SSAT-1 Activity as A Reliable Clinical Diagnostic Assay for Breast and Lung Cancer

“…We have recently reported that human cancer is associated with high urinary concentration of AA [15]. In the present study, we further validated the clinical utility of urinary AA concentration as a diagnostic marker for breast and lung cancer.…”

“…Recently, we have reported the clinical utility of amantadine to detect elevated SSAT-1 activity by measuring increased concentration of AA in the urine of cancer patients. This increase was supported by the increase of the SSAT-1 gene transcripts and protein contents in patient-derived tumor tissue [15]. While high levels of SSAT-1 gene and protein expression were measured in human primary breast, prostate and lung tumor tissue, an increase in the urinary concentration of AA in cancer patients was observed [15].…”

“…This increase was supported by the increase of the SSAT-1 gene transcripts and protein contents in patient-derived tumor tissue [15]. While high levels of SSAT-1 gene and protein expression were measured in human primary breast, prostate and lung tumor tissue, an increase in the urinary concentration of AA in cancer patients was observed [15]. The present study was undertaken to optimize urine collection time points for AA and further validate the use of amantadine as a mean to detect increases in SSAT-1 activity.…”

Predictive Value and Clinical Significance of Increased SSAT-1 Activity in Healthy Adults

“…They then ingested orally 200 mg (2 × 100 mg) amantadine capsules (Mylan-Amantadine, amantadine hydrochloride, USP). Urine was then collected at 2, 4 and 6 h postamantadine ingestion for analysis as previously described [20,21]. Participants that were deemed as outliers were consented for follow-up after obtaining appropriate approvals from the respective institutional review boards.…”

“…Amantadine is acetylated by SSAT-1 to produce acetylamantadine (AA) [18], which is a stable end product excreted in urine [18,19]. We have reported the clinical utility of amantadine to detect elevated SSAT-1 activity by measuring increased concentration of AA in the urine of cancer patients [20,21]. In earlier studies, a proportion of the healthy adult controls were deemed to be ‘outliers’ because of higher than expected AA concentrations in the urine.…”