Proteomic and transcriptomic study on the action of a cytotoxic saponin (Polyphyllin D): Induction of endoplasmic reticulum stress and mitochondria-mediated apoptotic pathways

Fung Ming Siu, Dik Lung Ma, Yee Wai Cheung, Chun Nam Lok, Kun Yan, Zhiqi Yang, Mengsu Yang, Song Xiao Xu, Chi Bun Ko, Qing Yu He, Chi Ming Che

Research output: Journal article publicationJournal articleAcademic researchpeer-review

75 Citations (Scopus)

Abstract

Polyphyllin D (PD) is a potent cytotoxic saponin found in Paris polyphylla. In the present study, bioinformatic, proteomic and transcriptomic analyses were performed to study the mechanisms of action of PD on human nonsmall cell lung cancer (NSCLC) cell line (NCI-H460). Using a gene expression-based bioinformatic tool (connectivity map), PD was identified as a potential ER stress inducer. Our proteomic and transcriptomic analyses revealed that PD treatment led to upregulation of typical ER stress-related proteins/genes including glucose-regulated protein 78 (BiP/GRP78) and protein disulfide isomerase (PDI). In particular, elevated expression of C/EBP homologous transcription factor (chop) and activation of caspase-4 occurred at early time point (8 h) of PD treatment, signifying an initial ER stress-mediated apoptosis. Induction of tumor suppressor p53, disruption of mitochondrial membrane, activation of caspase-9 and caspase-3 were detected upon prolonged PD treatment. Collectively, these data revealed that PD induced the cytotoxic effect through a mechanism initiated by ER stress followed by mitochondrial apoptotic pathway. The ability of activating two major pathways of apoptosis makes PD an attractive drug lead for anticancer therapeutics. KGaA.
Original languageEnglish
Pages (from-to)3105-3117
Number of pages13
JournalProteomics
Volume8
Issue number15
DOIs
Publication statusPublished - 1 Aug 2008

Keywords

  • Apoptosis
  • Lung cancer
  • Proteomics
  • Saponin
  • Transcriptomics

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

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