title: Litchi seed extracts diminish prostate cancer progression via induction of apoptosis and attenuation of EMT through Akt/GSK-3β signaling.
abstract: Litchi (Litchi chinensisSonnnerat, Sapindaceae), known as Chinese Cherry, is a subtropical fruit tree originating from southern China. Litchi seed extracts have diverse pharmacological effects, including anticancer. However, its anticancer effects and mechanisms on prostate cancer have not been determined. In this study, we used n-butyl alcohol extract of Litchi seed (NLS) to treat prostate cancer PC3, DU145, RM1 and C4-2B cells. NLS induced a significant decrease in cell viability and clonogenic growth in a dose-dependent manner. NLS induced cell apoptosis and cell cycle G1/S phase arrest by inactivating Akt signaling pathway, which were associated with activation of mitochondrial caspase-dependent apoptotic cascades, up-regulation of cyclin-dependent kinase (CDK) inhibitors p21 and p27, and inhibition of correlated cyclin/CDK network. In addition, NLS treatment significantly decreased cell migration and invasion via phenotypic inversion of EMT, correlated with increased expression of E-cadherin and β-catenin, and decreased expression of vimentin and snail, which is partially attributed to inhibiting Akt/GSK-3β signaling pathway. Finally, PC3 xenograft nude mice treated with NLS in vivo showed a significant decrease in tumor size without toxicity. These findings suggest that NLS has potential for development into a safe and potent alternative therapy for prostate cancer patients.
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.|Key Laboratory of Longevity and Aging-related Disease, Chinese Ministry of Education, 22 Shuangyong Road, Nanning 530021, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Guangxi University of Chinese Medicine, 179 Mingxiu Dong Road, Nanning 530001, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Luo
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 1600 Huron Parkway, Ann Arbor, MI 48109, USA.
authors.forename: Hebao
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.|Key Laboratory of Longevity and Aging-related Disease, Chinese Ministry of Education, 22 Shuangyong Road, Nanning 530021, China.|Xinxiang Central Hospital of Henan, 56 Jinsui Road, Xinxiang 453000, China.
authors.forename: Yudui
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 1600 Huron Parkway, Ann Arbor, MI 48109, USA.
authors.forename: Pan
authors.initials: P
authors.lastname: Shu
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.|Key Laboratory of Longevity and Aging-related Disease, Chinese Ministry of Education, 22 Shuangyong Road, Nanning 530021, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.|Key Laboratory of Longevity and Aging-related Disease, Chinese Ministry of Education, 22 Shuangyong Road, Nanning 530021, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.|Key Laboratory of Longevity and Aging-related Disease, Chinese Ministry of Education, 22 Shuangyong Road, Nanning 530021, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Urology and Pathology, School of Medicine, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.
authors.forename: Evan T
authors.initials: ET
authors.lastname: Keller
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Michigan, 1600 Huron Parkway, Ann Arbor, MI 48109, USA.
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Guangxi University of Chinese Medicine, 179 Mingxiu Dong Road, Nanning 530001, China.
authors.forename: Jiagang
authors.initials: J
authors.lastname: Deng
authors.affiliation: Center for Translational Medicine, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.|Key Laboratory of Longevity and Aging-related Disease, Chinese Ministry of Education, 22 Shuangyong Road, Nanning 530021, China.|Department of Urology and Pathology, School of Medicine, University of Michigan, 2800 Plymouth Road, Ann Arbor, MI 48109, USA.|Southern University of Science and Technology, School of Medicine, 1088 Xueyuan Blvd., Nanshan District, Shenzhen, 518055, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D006801:Humans; D032125:Litchi / Q000737:chemistry*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors / Q000378:metabolism; D014746:Vimentin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D015820:Cadherins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D010936:Plant Extracts; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D014746:Vimentin; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt