International Journal of Nanomedicine (Oct 2019)
Photoluminescent And Self-Assembled Hyaluronic Acid-Zinc Oxide-Ginsenoside Rh2 Nanoparticles And Their Potential Caspase-9 Apoptotic Mechanism Towards Cancer Cell Lines
Abstract
Yeon Ju Kim,1,* Haribalan Perumalsamy,1,* Verónica Castro-Aceituno,1 Donghyuk Kim,2 Josua Markus,1 Seungah Lee,3 Sung Kim,4 Ying Liu,1 Deok Chun Yang1 1Department of Oriental Medicinal Biotechnology and Graduate School of Biotechnology, College of Life Science, Kyung Hee University, Yongin-si, Gyeonggi-do, Republic of Korea; 2School of Energy and Chemical Engineering/School of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan, South Korea; 3Department of Applied Chemistry and Institute of Natural Sciences, College of Applied Science, Kyung Hee University, Seoul, Republic of Korea; 4Center for Global Converging Humanities, Kyung Hee University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Yeon Ju KimCollege of Life Sciences, Kyung Hee University, 1732, Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Republic of KoreaTel +82 31 201 2645Fax +82 31 204 8116Email [email protected]: Zinc oxide nanoparticles (ZnO NPs) are used in modern cancer therapy based on their specific target, efficacy, low toxicity and biocompatibility. The photocatalytic performance of Zinc oxide (ZnO) nanocomposites with hyaluronic acid (HA) was used to study anticancer properties against various human cancer cell lines.Methods: Zinc oxide (ZnO) nanocomposites functionalized by hyaluronic acid (HA) were prepared by a co-precipitation method (HA-ZnONcs). The submicron-flower-shaped nanocomposites were further functionalized with ginsenoside Rh2 by a cleavable ester bond via carbodiimide chemistry to form Rh2HAZnO. The physicochemical behaviors of the synthesized ZnO nanocomposites were characterized by various analytical and spectroscopic techniques. We carried out 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to evaluate the toxicity of Rh2HAZnO in various human cancer cells (A549, MCF-7, and HT29). Furthermore, to confirm the apoptotic effects of Rh2HAZnO and to determine the role of the Caspase-9/p38 MAPK pathways by various molecular techniques such as RT-PCR and Western blotting. Furthermore, Rh2HAZnO induced morphological changes of these cell lines, mainly intracellular reactive oxygen species (ROS) were observed by ROS staining and nucleus by Hoechst staining.Results: We confirmed that Rh2HAZnO exhibits the anti-cancer effects on A549 lung cancer, HT29 colon cancer, and MCF7 breast cancer cells. Moreover, intracellular reactive oxygen species (ROS) were observed in three cancer cell lines. Rh2HAZnO induced apoptotic process through p53-mediated pathway by upregulating p53 and BAX and downregulating BCL2. Specifically, Rh2HAZnO induced activation of cleaved PARP (Asp214) in A549 lung cancer cells and upregulated Caspase-9/phosphorylation of p38 MAPK in other cell lines (HT29 and MCF-7). Furthermore, Rh2HAZnO induced morphological changes in the nucleus of these cell lines.Conclusion: These results suggest that the potential anticancer activity of novel Rh2HAZnO nanoparticles might be linked to induction of apoptosis through the generation of ROS by activation of the Caspase-9/p38 MAPK pathway.Keywords: zinc oxide nanocomposites, ginsenoside Rh2, Dendropanax morbifera Léveille, cytotoxicity, anticancer activity, drug delivery
