Ethanol extracts of Hizikia fusiforme induce apoptosis in human prostate cancer PC3 cells via modulating a ROS-dependent pathway

Eun Choi; Hyesook Lee; Yung Choi; Eun Choi; Hyesook Lee; Yung Choi; Cheol Park; Gi-young Kim; You-jin Jeon; Hee-jae Cha; Suhkmann Kim; Heui-soo Kim; Hye Hwang

Return

Ethanol extracts of Hizikia fusiforme induce apoptosis in human prostate cancer PC3 cells via modulating a ROS-dependent pathway

Author: Eun CHOI ¹ ; Hyesook LEE ¹ ; Yung CHOI ¹ ; Eun CHOI ² ; Hyesook LEE ² ; Yung CHOI ² ; Cheol PARK ³ ; Gi-Young KIM ⁴ ; You-Jin JEON ⁴ ; Hee-Jae CHA ⁵ ; Suhkmann KIM ⁶ ; Heui-Soo KIM ⁷ ; Hye HWANG ⁸
Author Information

1. Anti-Aging Research Center, Dong-eui University
2. Department of Biochemistry, College of Korean Medicine, Dong-eui University
3. Department of Molecular Biology, College of Natural Sciences, Dong-eui University
4. Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University
5. Department of Parasitology and Genetics, Kosin University, College of Medicine
6. Department of Chemistry, College of Natural Sciences, Center for Proteome Biophysics and Chemistry, Institute for Functional Materials, Pusan National University
7. Department of Biological Sciences, College of Natural Sciences, Pusan National University
8. Department of Food and Nutrition, College of Nursing, Healthcare Sciences and Human Ecology, Dong-eui University
Publication Type:Journal Article
Keywords: Apoptosis; Caspase; Hizikia fusiforme; Prostate cancer cells; Reactive oxygen species
From:Asian Pacific Journal of Tropical Biomedicine 2020;10(2):78-86
CountryChina
Language:Chinese
Abstract: Objective: To investigate whether ethanol extracts of Hizikia fusiforme could induce apoptosis in human prostate cancer PC3 cells. Methods: Cell viability was evaluated using 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide. Apoptosis and mitochondrial membrane potential (MMP) were measured using flow cytometry in PC3 cells. DNA damage was assessed by nuclear staining and DNA fragmentation assay. Expressions of apoptosis-associated proteins were determined by Western blotting assays. Activities of caspase-3, -8, and -9 were determined by colorimetric assay. Moreover, intracellular reactive oxygen species (ROS) generation was detected using a flow cytometer and fluorescence microscope. Results: Treatment of PC3 cells with ethanol extracts of Hizikia fusiforme inhibited proliferation, which was associated with induction of apoptosis, and accompanied by increased expression of Fas, Fas-ligand (FasL), Bax and tBid, and decreased expression of Bcl-2. In addition, ethanol extracts of Hizikia fusiforme reduced c-Flip expression and activated caspase-8, -9 and -3, resulting in an increase in poly (ADP-ribose) polymerase (PARP)cleavage. However, in the presence of a pan-caspase inhibitor, ethanol extracts of Hizikia fusiforme-mediated growth inhibition and apoptosis were significantly attenuated. Ethanol extracts of Hizikia fusiforme also destroyed the integrity of mitochondria due to the loss of MMP, leading to cytosolic release of cytochrome c. Moreover, the levels of ROS were markedly increased by treatment with ethanol extracts of Hizikia fusiforme, which was significantly suppressed by the ROS scavenger N-acetyl-L-cysteine. Further investigation of whether ethanol extracts of Hizikia fusiforme-induced apoptosis was related to the generation of ROS was conducted and the results showed that N-acetyl-L-cysteine fully blocked ethanol extracts of Hizikia fusiforme-induced apoptotic events including loss of MMP, activation of caspase-3, the cytosolic release of cytochrome c and cytotoxicity. Conclusions: Ethanol extracts of Hizikia fusiforme have chemopreventive potential via induction of ROS-dependent apoptosis. Therefore, ethanol extracts of Hizikia fusiforme may be useful for developing effective and selective natural sources to inhibit cancer cell proliferation.