title: The triterpenoids of Hibiscus syriacus induce apoptosis and inhibit cell migration in breast cancer cells.
abstract: BACKGROUND
  Breast cancer-related mortality increases annually. The efficacy of current breast cancer treatments is limited, and they have numerous side effects and permit high recurrence. Patients with estrogen receptor (ER)-negative or triple-negative breast cancer are particularly difficult to treat. Treatment for this type of cancer is lacking, and its prognosis is poor, necessitating the search for alternative treatments.
  
  
  METHODS
  This study screened Chinese herb Hibiscus syriacus extracts and identified a novel anti-cancer drug for patients with ER-negative breast cancer. The inhibitory effects on cell viability and migration were evaluated for each compound, and the molecular regulatory effects were evaluated on both mRNA and protein levels.
  
  
  RESULTS
  We found several triterpenoids including betulin (K02) and its derivatives (K03, K04, and K06) from H. syriacus inhibited human triple-negative breast cancer cell viability and migration but revealed smaller cytotoxic effects on normal mammalian epithelial cells. Betulin and its derivatives induced apoptosis by activating apoptosis-related genes. In addition, they activated p21 expression, which induced cell cycle arrest in breast cancer cells. Betulin (K02) and betulinic acid (K06) had stronger inhibitory effects on cell viability and migration than K03 and K04.
  
  
  CONCLUSIONS
  H. syriacus extracts might inhibit breast cancer cell viability and induce apoptosis by activating p53 family regulated pathways and inhibiting AKT activation. H. syriacus extracts may provide important insight into the development of novel alternative therapies for breast cancer.
authors.affiliation: Department of Pathology, and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. hsurnai@gmail.com.|Biobank Management Center of Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. hsurnai@gmail.com.
authors.forename: Ren-Jun
authors.initials: RJ
authors.lastname: Hsu
authors.affiliation: Departments of Chinese Medicine, Chi-Mai Medical Center, Tainan, Taiwan. cmh7100@mail.chimei.org.tw.
authors.forename: Yao-Chin
authors.initials: YC
authors.lastname: Hsu
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Chang Gung Children's Hospital, Taoyuan, Taiwan. vic102535@yahoo.com.tw.
authors.forename: Shu-Pin
authors.initials: SP
authors.lastname: Chen
authors.affiliation: Department of Pathology, and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. ll26656234@hotmail.com.
authors.forename: Chia-Lynn
authors.initials: CL
authors.lastname: Fu
authors.affiliation: Department of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. doc20106@ndmctsgh.edu.tw.
authors.forename: Jyh-Cherng
authors.initials: JC
authors.lastname: Yu
authors.affiliation: Department of Obstetrics & Gynecology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. doc30666@gmail.com.
authors.forename: Fung-Wei
authors.initials: FW
authors.lastname: Chang
authors.affiliation: Department of Emergency Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. chen.yinghsin@gmail.com.
authors.forename: Ying-Hsin
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Division of Urology, Department of Surgery, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan. mento1218@gmail.com.
authors.forename: Jui-Ming
authors.initials: JM
authors.lastname: Liu
authors.affiliation: Department of Pathology, and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. jaryiho@gmail.com.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. jaryiho@gmail.com.
authors.forename: Jar-Yi
authors.initials: JY
authors.lastname: Ho
authors.affiliation: Department of Pathology, and Graduate Institute of Pathology and Parasitology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. cpyupath@yahoo.com.tw.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan. cpyupath@yahoo.com.tw.
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D031584:Hibiscus; D006801:Humans; D053978:Pentacyclic Triterpenes; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D014315:Triterpenes / Q000494:pharmacology* / Q000627:therapeutic use; D000094062:Betulinic Acid
chemical_list: D000970:Antineoplastic Agents; D053978:Pentacyclic Triterpenes; D010936:Plant Extracts; D014315:Triterpenes; C002503:betulin; D000094062:Betulinic Acid