title: SB365, Pulsatilla saponin D, suppresses the growth of gefitinib-resistant NSCLC cells with Met amplification.
abstract: Clinical treatment using epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) such as gefitinib or erlotinib has been applied in patients with non-small cell lung cancers (NSCLCs). Unfortunately, acquired drug resistance emerges in these patients due to the amplification of the Met proto-oncogene, which may be a compensatory mechanism of NSCLCs against EGFR inhibition. To overcome this resistance, identification of new small-molecule natural compounds is crucial for cancer therapeutics. In this regard, SB365, saponin D from the root of Pulsatilla koreana which has been used as a traditional medicine in Korea for several diseases, has attracted wide interest. In the present study, SB365 effectively suppressed the proliferation of gefitinib-resistant HCC827GR NSCLC cells with Met amplification. Notably, our data revealed that SB365 inhibited the phosphorylation of Met and the downstream signaling pathway required for growth and survival in the Met-amplified HCC827GR cells. Moreover, SB365 suppressed the anchorage-independent growth, migration and invasion along with induction of apoptosis in the HCC827GR cells. Therefore, these results suggest that SB365 is good candidate as a natural product for use in the treatment of Met-amplified NSCLCs.
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Won-Jun
authors.initials: WJ
authors.lastname: Jang
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Byoungduck
authors.initials: B
authors.lastname: Park
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Gil-Saeng
authors.initials: GS
authors.lastname: Jeong
authors.affiliation: Department of Biomedical Sciences, College of Medicine, Inha University, Incheon, Republic of Korea.
authors.forename: Soon-Sun
authors.initials: SS
authors.lastname: Hong
authors.affiliation: College of Pharmacy, Keimyung University, Daegu 704-701, Republic of Korea.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Jeong
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D000077156:Gefitinib; D006801:Humans; D000090063:Proto-Oncogene Mas; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D031946:Pulsatilla / Q000737:chemistry; D011799:Quinazolines / Q000627:therapeutic use; D012503:Saponins / Q000008:administration & dosage*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D011799:Quinazolines; D012503:Saponins; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met; D000077156:Gefitinib