Login to Access Video or Poster Abstract: MP83-20
Sources of Funding: National Natural Science Foundation of China (No.81370858 and 81570683), and grant from Beijing Natural Science Foundation (No.7142161)

Introduction

Recently, sulfur dioxide (SO2), similar to nitric oxide and hydrogen sulfide, has been recognized as a new kind of gasotransmitter. It can be endogenously produced from metabolism of the sulfur-containing amino acid L-cysteine by SO2 synthase, aspartate aminotransferase (AAT), in mammal tissues including urogenital system. Besides, studies proved SO2 had physiological and pathophysiological significance among humans. Here, we'd like to explore the effects of endogenous SO2 on prostate cancer (PCa).

Methods

The expression of AAT1 in human PCa and benign prostatic hyperplasia (BPH), is detected by immunohistochemistry. The SO2 concentrations of prostate from transgenic adenocarcinoma of the mouse prostate (TRAMP) model and that from parental C57BL/6 mouse were measured using high-performance liquid chromatography (HPLC). Bisulfite and sulfite were regarded as SO2 donors. The silenced or overexpressed AAT1/AAT2 PCa cell lines were conducted to further study the role of endogenous SO2. Cell proliferation was determined by Cell Counting Kits-8. And cyclins and cyclin-dependent kinases were analyzed by western blot.

Results

Compared with human BPH, PCa displayed less AAT1 expression (A). Besides, HPLC showed a lower level of SO2 concentration in prostate from TRAMP mouse than that from parental C57BL/6 mouse (B). Silenced/overexpressed AAT1 in PCa cell lines, C4-2 or CWR22Rv1, could promote/suppress their proliferation (C). Furthermore, cyclin, cyclinD1, and cyclin-dependent kinase, CDK6, were reduced/increased among AAT1/AAT2 overexpressed/silenced PCa cell lines (D).

Conclusions

SO2, a novel gasotransmitter, and its synthesis enzyme AAT are frequently downregulated in PCa. Endogenous SO2 could function as a tumor suppressor via regulating the proliferation of PCa. Moreover, CyclinD1 and CDK6 would be involved in the regulation of SO2.

Funding

National Natural Science Foundation of China (No.81370858 and 81570683), and grant from Beijing Natural Science Foundation (No.7142161)