Antihepatoma peptide,scolopentide,derived from the centipede scolopendra subspinipes mutilans  

作　　者：Yu-Xing Hu Zhuo Liu Zhen Zhang Zhe Deng Zhen Huang Ting Feng Qing-Hong Zhou Si Mei Chun Yi Qing Zhou Pu-Hua Zeng Gang Pei Sha Tian Xue-Fei Tian 

机构地区：[1]College of Integrated Chinese and Western Medicine,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China [2]Hunan Key Laboratory of Translational Research in Formulas and Zheng of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China [3]Department of Scientific Research,Hunan Academy of Traditional Chinese Medicine Affiliated Hospital,Changsha 410208,Hunan Province,China [4]Hunan Province University Key Laboratory of Oncology of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China [5]Department of Pediatric,Shenzhen Hospital of Beijing University of Chinese Medicine,Shenzhen 518000,Guangdong Province,China [6]Department of Physiology,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China [7]Department of Pathology,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China [8]Department of Andrology,First Hospital of Hunan University of Chinese Medicine,Changsha 410007,Hunan Province,China [9]Department of Oncology,Hunan Academy of Traditional Chinese Medicine Affiliated Hospital,Changsha 410208,Hunan Province,China [10]College of Pharmacy,Hunan University of Chinese Medicine,Changsha 410208,Hunan Province,China [11]Dr Neher’s Biophysics Laboratory for Innovative Drug Discovery,Macao University of Science and Technology,Macao 999078,China

出　　处：《World Journal of Gastroenterology》2023年第12期1875-1898,共24页世界胃肠病学杂志（英文版）

基　　金：Supported by the National Natural Science Foundation of China,No.U20A20408 and No.82074450;Natural Science Foundation of Hunan Province,No.2020JJ4066 and No.2021JJ40405;Key scientific research project of Hunan Education Department,No.21A0243;Key project of academician workstation guidance project,No.21YSZQ007.

摘　　要：BACKGROUND Centipedes have been used to treat tumors for hundreds of years in China.However,current studies focus on antimicrobial and anticoagulation agents rather than tumors.The molecular identities of antihepatoma bioactive components in centipedes have not yet been extensively investigated.It is a challenge to isolate and characterize the effective components of centipedes due to limited peptide purification technologies for animal-derived medicines.AIM To purify,characterize,and synthesize the bioactive components with the strongest antihepatoma activity from centipedes and determine the antihepatoma mechanism.METHODS An antihepatoma peptide(scolopentide)was isolated and identified from the centipede scolopendra subspinipes mutilans using a combination of enzymatic hydrolysis,a Sephadex G-25 column,and two steps of high-performance liquid chromatography(HPLC).Additionally,the CCK8 assay was used to select the extracted fraction with the strongest antihepatoma activity.The molecular weight of the extracted scolopentide was characterized by quadrupole time of flight mass spectrometry(QTOF MS),and the sequence was matched by using the Mascot search engine.Based on the sequence and molecular weight,scolopentide was synthesized using solid-phase peptide synthesis methods.The synthetic scolopentide was confirmed by MS and HPLC.The antineoplastic effect of extracted scolopentide was confirmed by CCK8 assay and morphological changes again in vitro.The antihepatoma effect of synthetic scolopentide was assessed by the CCK8 assay and Hoechst staining in vitro and tumor volume and tumor weight in vivo.In the tumor xenograft experiments,qualified model mice(male 5-week-old BALB/c nude mice)were randomly divided into 2 groups(n=6):The scolopentide group(0.15 mL/d,via intraperitoneal injection of synthetic scolopentide,500 mg/kg/d)and the vehicle group(0.15 mL/d,via intraperitoneal injection of normal saline).The mice were euthanized by cervical dislocation after 14 d of continuous treatment.Mechanistically,flow cytometry

关 键 词：SCOLOPENDRA CENTIPEDE Antihepatom peptide Hepatocellular carcinoma Death receptor 4 Death receptor 5 

分 类 号：R284[医药卫生—中药学]