3-Bromopyruvate induces endoplasmic reticulum stress, overcomes autophagy and causes apoptosis in human HCC cell lines

Shanmugasundaram Ganapathy-Kanniappan, Jean Francois H. Geschwind, Rani Kunjithapatham, Manon Buijs, Labiq H. Syed, Pramod P. Rao, Shinichi Ota, Byung Kook Kwak, Romaric Loffroy, Mustafa Vali

Research output: Contribution to journalArticlepeer-review

48 Scopus citations


Background: Autophagy, a cellular response to stress, plays a role in resistance to chemotherapy in cancer cells. Resistance renders systemic chemotherapy generally ineffective against human hepatocellular carcinoma (HCC). Recently, we reported that the pyruvate analog 3-bromopyruvate (3-BrPA) promoted tumor cell death by targeting GAPDH. In continuance, we investigated the intracellular response of two human HCC cell lines (Hep3B and SK-Hep1) that differ in their status of key apoptotic regulators, p53 and Fas. Methods and Results: 3-BrPA treatment induced endoplasmic reticulum (ER) stress, translation inhibition and apoptosis based on Western blot and qPCR, pulse labeling, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay and active caspase-3 in both the cell lines. However, electron microscopy revealed that 3-BrPA treated SK-Hep1 cells underwent classical apoptotic cell death while Hep3B cells initially responded with the protective autophagy that failed to prevent eventual apoptosis. Conclusion: 3-BrPA treatment promotes apoptosis in human HCC cell lines, irrespective of the intracellular response.

Original languageEnglish (US)
Pages (from-to)923-926
Number of pages4
JournalAnticancer Research
Issue number3
StatePublished - Mar 1 2010


  • Antiglycolytic
  • Autophagosome
  • ER stress
  • Translation inhibition

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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