title: Elimination of cancer stem-like side population in human glioblastoma cells accompanied with stemness gene suppression by Korean herbal recipe MSC500.
abstract: BACKGROUND
  High-grade gliomas are the most common and invasive malignant brain tumors in adults, and they are almost universally fatal because of drug resistance and recurrence. In spite of the progress in adjuvant therapy (like temozolomide) and irradiation after surgery, no effective salvage therapy is currently available for relapsed patients. A Korean herbal recipe MSC500 has been reported to have beneficial therapeutic effects in patients with high-grade gliomas who are relapsed or refractory to conventional treatments. But the underlying molecular mechanisms remain unclear.
  
  
  METHODS
  As Cancer stem cell (CSC) plays a pivotal role in the resistance to conventional cancer therapy, we explored the effects of MSC500 on the CSC-like side population (SP) in GBM8401 human glioblastoma multiforme cells.
  
  
  RESULTS
  Compared with the parental cells, the SP cells were more resistant to temozolomide but sensitive to MSC500. The mRNA levels of stemness genes such as Nanog, CD133, and ABCG2 were much higher in the SP cells, and so was E-cadherin, which was reported to correlate with the aggressiveness of glioblastoma multiforme. Treatment with MSC500 decreased the proportion of SP cells and high ALDH activity cells from 1.6% to 0.3% and from 0.9% to 0.1%, respectively, accompanied with suppression of the aforementioned stemness genes and E-cadherin, as well as other CSC markers such as ABCB5, Oct-4, Sox-2, β-catenin, Gli-1, and Notch-1.
  
  
  CONCLUSIONS
  Our results suggest the potential role of MSC500 as an integrative and complementary therapeutic for advanced or refractory high-grade glioma patients.
authors.affiliation: Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Jung
authors.initials: CJ
authors.lastname: Yao
authors.affiliation: Banronginsu Oriental Medicine Clinic, Seoul, Korea.
authors.forename: Tae-Young
authors.initials: TY
authors.lastname: Han
authors.affiliation: Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ping-Hsiao
authors.initials: PH
authors.lastname: Shih
authors.affiliation: Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tsu-Yi
authors.initials: TY
authors.lastname: Yi
authors.affiliation: Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: I-Chun
authors.initials: IC
authors.lastname: Lai
authors.affiliation: Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ken-Hu
authors.initials: KH
authors.lastname: Chang
authors.affiliation: Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Tung-Yuan
authors.initials: TY
authors.lastname: Lai
authors.affiliation: Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chia-Lun
authors.initials: CL
authors.lastname: Chang
authors.affiliation: Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan National Institute of Cancer Research, National Health Research Institutes, Zhunan, Taiwan gminlai@nhri.org.tw.
authors.forename: Gi-Ming
authors.initials: GM
authors.lastname: Lai
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D002648:Child; D000529:Complementary Therapies / Q000379:methods; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D008297:Male; D055670:Medicine, Korean Traditional; D014411:Neoplastic Stem Cells / Q000187:drug effects; D028321:Plant Preparations / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D028321:Plant Preparations; D012333:RNA, Messenger
keywords: ALDH; E-cadherin; MSC500; cancer stem cell; glioma