title: Linalool-Incorporated Nanoparticles as a Novel Anticancer Agent for Epithelial Ovarian Carcinoma.
abstract: Although cytotoxic chemotherapy is widely used against epithelial ovarian cancer (EOC), adverse side effects and emergence of resistance can limit its utility. Therefore, new drugs with systemic delivery platforms are urgently needed for this disease. In this study, we developed linalool-incorporated nanoparticles (LIN-NP) as a novel anticancer agent. We prepared LIN-NPs by the self-assembly water-in-oil-in-water (w/o/w) emulsion method. LIN-NP-mediated cytotoxicity and apoptosis was assessed in EOC cells, and the role of reactive oxygen species (ROS) generation as the mechanism of action was evaluated. In addition, therapeutic efficacy of LIN-NP was assessed in cell lines and patient-derived xenograft (PDX) models for EOC. LIN-NPs had significant cytotoxicity and apoptotic activity against EOC cells, including A2780, HeyA8, and SKOV3ip1. LIN-NP treatment increased apoptosis in EOC cells through ROS generation and a subsequent decrease in mitochondrial membrane potential and increase in caspase-3 levels. In addition, 100 mg/kg LIN-NPs significantly decreased tumor weight in the HeyA8 (P < 0.001) and SKOV3ip1 (P = 0.006) in vivo models. Although treatment with 50 mg/kg LIN-NP did not decrease tumor weight compared with the control group, combination treatment with paclitaxel significantly decreased tumor weight compared with paclitaxel alone in SKOV3ip1 xenografts (P = 0.004) and the patient-derived xenograft model (P = 0.020). We have developed LIN-NPs that induce ROS generation as a novel anticancer agent for EOC. These findings have broad applications for cancer therapy. Mol Cancer Ther; 15(4); 618-27. ©2016 AACR.
authors: Department of Immunology, School of Medicine, Konkuk University, Chungju, South Korea.
authors: Hee Dong
authors: HD
authors: Han
authors: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea.
authors: Young-Jae
authors: YJ
authors: Cho
authors: Research Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Daejeon, South Korea.
authors: Sung Keun
authors: SK
authors: Cho
authors: Department of Immunology, School of Medicine, Konkuk University, Chungju, South Korea.
authors: Yeongseon
authors: Y
authors: Byeon
authors: Department of Immunology, School of Medicine, Konkuk University, Chungju, South Korea.
authors: Hat Nim
authors: HN
authors: Jeon
authors: Department of Pathology, Cheil General Hospital and Women's Healthcare Center, Dankook University College of Medicine, Gyeonggi-do, South Korea.
authors: Hye-Sun
authors: HS
authors: Kim
authors: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Byoung-Gie
authors: BG
authors: Kim
authors: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Duk-Soo
authors: DS
authors: Bae
authors: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Gabriel
authors: G
authors: Lopez-Berestein
authors: Department of Cancer Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas. Center for RNA Interference and Non-coding RNA, The University of Texas MD Anderson Cancer Center, Houston, Texas. Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors: Anil K
authors: AK
authors: Sood
authors: Research Center for Medicinal Chemistry, Korea Research Institute of Chemical Technology, Daejeon, South Korea. garden.lee@samsung.com bcshin@krict.re.kr immun3023@kku.ac.kr.
authors: Byung Cheol
authors: BC
authors: Shin
authors: Department of Immunology, School of Medicine, Konkuk University, Chungju, South Korea. garden.lee@samsung.com bcshin@krict.re.kr immun3023@kku.ac.kr.
authors: Yeong-Min
authors: YM
authors: Park
authors: Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul, South Korea. garden.lee@samsung.com bcshin@krict.re.kr immun3023@kku.ac.kr.
authors: Jeong-Won
authors: JW
authors: Lee
mesh_terms: D000080462:Acyclic Monoterpenes; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D000077216:Carcinoma, Ovarian Epithelial; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D039821:Monoterpenes / Q000008:administration & dosage* / Q000737:chemistry; D053758:Nanoparticles / Q000737:chemistry; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000080462:Acyclic Monoterpenes; D000970:Antineoplastic Agents; D039821:Monoterpenes; D017382:Reactive Oxygen Species; C018584:linalool; D017239:Paclitaxel