Tingting Chen,1,2,* Bingxiang Ma,1,2,* Shi Lu,1,2 Lupeng Zeng,1,2 Huaying Wang,1,2 Wanhua Shi,1,2 Linying Zhou,3 Yaokun Xia,4 Xi Zhang,1 Jing Zhang,5 Jinghua Chen1 1School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 2Fujian Key Laboratory of Drug Target Discovery and Structural and Functional Research, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 3Electron Microscopy Facility, Public Technology Service Center, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 4Key Laboratory of the Ministry of Education for Gastrointestinal Cancer, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China; 5Department of Chemical Biology, College of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, Fujian Province, 350002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jinghua Chen, School of Pharmacy, Fujian Medical University, Fuzhou, Fujian Province, 350108, People’s Republic of China, Tel +86 591-22862016, Fax +86 591-22862016, Email cjh_huaxue@126.com; xz@fjmu.edu.cnPurpose: In recent years, a variety of nanoparticles with excellent anticancer and delivery properties have emerged for cancer therapy. However, potential toxicity, high production cost and complex preparation procedures have been obstacles to their use in biomedicine. Here, we obtained cucumber-derived nanovesicles (CDNVs) at high yield and low cost by simple juicing and ultracentrifugation. The anticancer effects of CDNVs were evaluated in vitro and in vivo.Methods: Transmission electron microscope, nanoparticle tracking analysis and laser particle size analysis were used to characterize the morphology, diameter and zeta potential of CDNVs, respectively. The anticancer effects of CDNVs in vitro were evaluated by MTT and apoptosis assays. The mechanism was further explored by measuring the protein levels of signal transducer and activator of transcription 3 pathway, reactive oxygen species, cell cycle distribution and caspase activity. In-vivo anticancer efficacy was evaluated by measuring tumor volume and weight of mice in three different treatment groups (CDNVs, cucurbitacin B and PBS).Results: CDNVs inhibited proliferation of human non-small cell lung cancer cells by suppressing signal transducer and activator of transcription 3 activation, generating reactive oxygen species, promoting cell cycle arrest, and activating the caspase pathway. These CDNVs exhibited strong anticancer effects both in vitro and in vivo, and reduced the rate of tumor growth without obvious toxicity to mouse visceral organs. Compared with an equivalent dose of cucurbitacin B, CDNVs exerted stronger anticancer effects in vitro and in vivo.Conclusion: These results demonstrate that CDNVs suppress tumor growth. This study addresses the development of cancer therapeutic drugs using plant-derived nanovesicles that are cost-efficient, simple to produce in high yields, and provide an alternative approach to drug isolation that may help advance sustainability of medicinal plants.Keywords: ROS, STAT3, cucurbitacin B, anticancer
