16:00 - 18:00
Room: Poster Area - Poster Shed
Poster Presentation
Antileukemia effect of Xestoquinone, induced apoptosis via oxidative stress combined with inhibition of Hsp90 and topoisomerase II activities
Shou-Ping Shih 1, 2, You-Ying Chen 3, Chun-Lin Chen 4, Steve Sheng-Fa Yu 1, 2, Mei-Chin Lu 5, 6
1 Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Koashiung
2 Doctoral Degree Program in Marine Biotechnology, Academia Sinica,, Taipei
3 Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Koashiung
4 Department of Biological Sciences, National Sun Yat-sen University, Koashiung
5 Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung
6 National Museum of Marine Biology & Aquarium, Pingtung

Xestoquinone (XQ), a polycyclic quinone-type metabolite, was isolated from the marine sponge Petrosia sp. which were found to inhibit a variety of cancer cell proliferation[1]. The marine polycyclic quinone-type metabolite, xestoquinone (XQ) was found to inhibit the proliferation of Molt 4, K562, SupT1, U937, T47D and DLD-1 cancer cell lines, with IC50 of 1.69, 4.71, 5.87, 11.65, 14.41 and 12.5 μM, respectively.It exhibited the most potent activity against leukemia Molt 4 cells.To fully understand the mechanism of XQ, we further explored the precise molecular targets in leukemia Molt 4 cells.We found that the use of HQ increased apoptosis by 20.8%-63.0% and caused disruption of mitochondrial membrane potential (MMP) by 30.3%-88.7% in a dose-dependent manner, as demonstrated by annexin-V/PI and JC-1 staining assays, respectively. Moreover, our findings indicated that the pretreatment of Molt 4 cells with N-acetyl-L-cysteine (NAC), a reactive oxygen species (ROS) scavenger, diminished MMP disruption and apoptosis induced by XQ, suggesting that ROS overproduction plays a crucial rule in the cytotoxic activity of XQ.The results of a cell-free system assay indicated that XQ could act as HDAC and topoisomerase inhibitor through the inhibition of pan-HDAC and topoisomerase IIα expression, respectively. On the protein level, the expression of the anti-apoptotic proteins p-Akt, HDAC, XIAP and Bcl-2 were inhibited by the use of XQ. However, the expression of the pro-apoptotic protein Bax, PARP cleavage and caspase activation, as well as Hsp70 and acetylated tubulin were increased after XQ treatment. Taken together, our results suggested that the antileukemic effect of XQ is ROS-mediated mitochondrial apoptosis combined with the inhibitory effect on Hsp90 and topoisomerase activities.

[1]Du L, Mahdi F, Datta S, Jekabsons MB, Zhou YD, Nagle DG. J. Nat. Prod. 2012, 9:1553-1559.


Reference:
Poster Session-PO-89:
Session:
Poster Presentation-1
Presenter/s:
Shou-Ping Shih
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