16:00 - 18:00
Room: Poster Area - Poster Shed
Poster Presentation
Heteronemin, Induced Mitochondrial Superoxide Production and Cytoskeleten protein Talin Dysfunction Mediated Leukemia Molt 4 cells Apoptosis.
Bo-Rong Peng 1, 2, Yu-Cheng Chen 3, 5, Ping-jyun Sung 4, 5, Mei-Chin Lu 4, 5
1 Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung
2 Doctoral Degree Program in Marine Biotechnology, Academia Sinica, Taipei
3 The PhD Program of Cancer Biology and Drug discovery, China Medical University, Taichung
4 Graduate Institute of Marine Biology, National Dong Hwa University, Pingtung
5 National Museum of Marine Biology & Aquarium, Pingtung

A sesterterpene derivative, heteronemin[1] exhibited potent cytotoxic activity against several cancer cell lines. To evaluate its cytotoxic mechanism of action, we first determined of heteronemin against several cancer cell lines for 24 and 48 h with MTT assay. The most sensitive cancer cell line was Molt4 . Thus, Molt4 cells were subjected to further investigation and the apoptotic inductive effect of heteronemin on these cells was evaluated using annexin V FITC assay. The use of increasing doses of heteronemin increased the percentage of apoptotic cells from 3.7% to 97.3%. Moreover, the apoptotic effect of heteronemin was further supported with DNA ladder formation, morphology change, caspases -3, -8, and -9 activation as well as PARP cleavage. Heteronemin induced accumulation of reactive oxygen species and superoxide ions in Molt 4 cells. The use of ROS scavenger, N-acetyl cysteine, suppressed the generation of ROS production from mitochondria which was induced by heteronemin treatment. Heteronemin also decreased talin expression but activated p-talin expression, an integrin regulatory protein. The pretreatment of Molt4 cells with talin siRNA enhanced the expression of talin regulated protein FAK and FAK-related signaling pathways p-AKT (ser473), NF-kB (p65), p-ERK and anti-apoptosis protein XIAP as well as it decreased the ability of heteronemin to induce cell death. We further expanded our investigation to evaluate the antitumor effect of heteronemin in vivo xenograft animal model. The administration of heteronemin (0.3125 μg/g) reduced tumor volume 60% compared with the control group. Taken together, these findings suggest the antitumor effect of heteronemin is associated with oxidative stress that the modulated talin and p-talin expression and mitochondrial dysfunction. Therefore, heteronemin represents an interesting anticancer drug lead against leukemia.

[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-93:
Session:
Poster Presentation-1
Presenter/s:
Bo-Rong Peng
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