journal contribution
posted on 2023-04-03, 15:49 authored by Hee Dong Han, Young-Jae Cho, Sung Keun Cho, Yeongseon Byeon, Hat Nim Jeon, Hye-Sun Kim, Byoung-Gie Kim, Duk-Soo Bae, Gabriel Lopez-Berestein, Anil K. Sood, Byung Cheol Shin, Yeong-Min Park, Jeong-Won Lee Safety and toxicity in mouse after treatment of linalool with different dose.
Funding
National Research Foundation of Korea (NRF)
National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning
Korean Health Technology R&D project through the Korean Health Industry Development Institute funded by Ministry for Health and Welfare, Republic of Korea
National R&D program for Cancer Control, Ministry for Health, Welfare and Family affairs, Republic of Korea
History
ARTICLE 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.
