16:00 - 18:00
Room: Poster Area - Poster Shed
Poster Presentation
Heteronemin, Marine Sesterpenoids-Type Metabolite, Induces Prostate LNcap Cells Apoptosis via Oxidative and ER Stress.
Mei-Chin Lu 1, 2, You-Ying Chen 3, Shou-Ping Shih 4, 5, Bo-Rong Peng 4, 5
1 Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung
2 National Museum of Marine Biology & Aquarium, Pingtung
3 Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung
4 Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung
5 Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei

Heteronemin, a marine sesterterpenoid-type natural product, possesses diverse bioactivities, especially antitumor effect[1]. To fully understand the antitumor mechanism of heteronemin, we further explored the precise molecular targets in prostate cancer cells. Initially, the growth inhibition effect of heteronemin was determined using MTT and colony formation assays. It exhibited the most potent activity against prostate cancer LNcap. With the xenograft animal model, the tumor size was significantly suppressed in the heteronemin-treated group about 51.88% as compared to the control group with no significant difference in the mice body weights. In addition, the results of a cell-free system assay demonstrated the inhibitory activity of heteronemin on Topoisomerase II (topo II). We found that the use of heteronemin triggered apoptosis by 20.13%-68.27%, caused disruption of mitochondrial membrane potential (MMP) by 66.92%-99.12% and elevated the calcium release by 1.80, 1.97 and 2.06 folds compared with the control group in a dose-dependent manner, as demonstrated by annexin-V/PI, Rhodamin 123 and Fluo-3 staining assays, respectively. Moreover, our findings indicated that the pretreatment of LNcap cells with an inhibitor of protein tyrosine phosphatase (PTPi) diminished ROS generation and apoptosis induced by heteronemin, suggesting that PTP activation plays a crucial rule in the cytotoxic activity of heteronemin.The expression of Hsp90 client proteins, phosphorylation of Akt (Ser473), STAT 3 (Ser 727 and Tyr705), PCNA, Rb2, as well as XIAP were suppressed by the use of heteronemin. However, the expression of p-HSF1, Hsp70 and acetylated tubulin were induced after heteronemin treatment. Thus, heteronemin significantly induced apoptotic and autophagic death of LNcap cells by modulating ER and oxidative stress combined with the inhibition of topo II catalytic activity and Hsp 90 function.

[1] Chang, Y.-C.; Tseng, S.-W.; Liu, L.-L.; Chou, Y.; Ho, Y.-S.; Lu, M.-C.; Su, J.-H. Mar. Drugs 2012, 10, 987-997.


Reference:
Poster Session-PO-94:
Session:
Poster Presentation-1
Presenter/s:
Mei-Chin Lu
Presentation type:
Poster presentation
Room:
Poster Area - Poster Shed
Date:
Monday, 27th August, 2018
Time:
16:00 - 18:00
Session times:
16:00 - 18:00