title: Anti-proliferative effect of Jesridonin on paclitaxel-resistant EC109 human esophageal carcinoma cells.
abstract: Chemoresistance to anticancer drugs is a major obstacle in the efforts to develop a successful treatment strategy for esophageal squamous carcinoma (ESCC). Thus, the exploration of new drugs and treatment strategies for combating resistance are of utmost importance. In this study, we investigated the antitumor drug resistance activity of Jesridonin, a new ent-kaurene diterpenoid, and its possible mechanisms of action using the resistant cancer cell line, EC109/Taxol. MTT assay revealed that Jesridonin had similar IC50 values against EC109 paclitaxel-sensitive cells and drug-resistant EC109/Taxol cells in vitro. In mice, Jesridonin effectively prevented the growth of EC109/Taxol tumor xenografts without exerting any significant toxicity. In addition, Jesridonin significantly inhibited the proliferation of EC109/Taxol cells, induced apoptosis and arrested the cell cycle at the G2/M phase. Furthermore, western blot analysis revealed that Jesridonin upregulated the expression of p53, p53 upregulated modulator of apoptosis (PUMA), cleaved-caspase-9 and cleaved-caspase-3 in EC109/Taxol cells, and downregulated the expression of procaspase-3, procaspase-9 and Bcl-2 in the EC109/Taxol cells in a concentration-dependent manner. Overall, our results demonstrate that Jesridonin may have potential for use in the treatment of paclitaxel-resistant ESCC. The data of the present study may lead to the development of novel treatment strategies for paclitaxel-resistant tumors.
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Basic Medicine, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Liubin
authors.initials: L
authors.lastname: Guo
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Saiqi
authors.initials: S
authors.lastname: Wang
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Li
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Dou
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Ran
authors.initials: R
authors.lastname: Wang
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Hongge
authors.initials: H
authors.lastname: Shi
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ke
authors.affiliation: Key Laboratory of Technology of Drug Preparation (Zhengzhou University), Ministry of Education of China, Zhengzhou, Henan 450001, P.R. China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Liu
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D006801:Humans; D051379:Mice; D014411:Neoplastic Stem Cells / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; C000606573:jesridonin; D017239:Paclitaxel