海洋放線菌二次代謝物Lu01-M藉由降低粒線體膜電位抑制前列腺癌細胞增生
李懿倫1、林詠琇2、李宗熹1、李威明1、劉家駒1、呂美津2,3
1衛生福利部屏東醫院泌尿科；2國立東華大學海洋生物研究所；3屏東海洋生物博物館
Marine actinomycete secondary metabolite Lu01-M Inhibited Prostate Cancer Cells Proliferation by Reducing Mitochondrial Membrane Potential
Yi-Lun Lee1, Yong-Shiou Lin2, Tsung-Hsi Lee1, Wei-Ming Li1, Chia-Chu Liu, Mei-Chin Lu,2,3
1Department of Urology, Pingtung Hospital, Ministry of Health and Welfare, Pingtung, Taiwan; 2Graduate Institute of Marine Biology, National Dong Hwa University; 3National Museum of Marine Biology & Aquarium, Pingtung, Taiwan
Purpose: The incidence of prostate cancer is growing in Taiwan males. More and more research shows that the secondary metabolites from marine actinomycetes could be the novel sources of drug development. Lu01-M which was extracted from the marine actenomycete exhibited potent cytotoxic effects in many cancer cell lines. The aim of this study is to investigate the molecular mechanisms of Lu01-M inciting mitochondrial injury in prostate cancer cells.
Materials and Methods: The cytotoxic activity of Lu01-M was evaluated by MTT assay. Human prostate cell line PC3 was incubated for in vitro studies. Xenograft was established in nude mice as in vivo animal model. The apoptotic cells were measured via annexin V/PI staining. Mitochondrial membrane potential(MMP), reactive oxygen species(ROS) and calcium release were determined by flow cytometery with specific fluorescent dyes. The expressions of biomarkers related to DNA damage were assessed by Western blots.
Results: Lu01-M has anti-prostate cancer effect and the most sensitive cancer cell line was PC3, with IC50 2.45±0.27 μg/mL after 24 hours treatment. Thus, PC3 cells were subjected to further investigation. Lu01-M expressed the ability to inhibit prostate cancer cells proliferation and migration. The use of affiliating doses of Lu01-M (0 to 6.25 μg/mL) increased the percentage of disruption of mitochondrial membrane potential, induced the reactive oxygen species to exhibit cytotoxic effects in prostate cancer cells. We further expanded our investigation to evaluate the antitumor effect of Lu01-M in vivo xenograft animal models. Animal experiments revealed that Lu01-M could inhibit prostate cancer cells proliferation and migration.
Conclusions: We found that the use of Lu01-M caused disruption of mitochondrial membrane potential (MMP) and promoted calcium release compared with the control group in a dose-dependent manner. Taken together, marine actenomycete secondary metabolite Lu01-M presented as an interesting candidate for its future therapeutic potential for prostate cancer.