TY - JOUR
T1 - 3-Bromopyruvate induces endoplasmic reticulum stress, overcomes autophagy and causes apoptosis in human HCC cell lines
AU - Ganapathy-Kanniappan, Shanmugasundaram
AU - Geschwind, Jean Francois H.
AU - Kunjithapatham, Rani
AU - Buijs, Manon
AU - Syed, Labiq H.
AU - Rao, Pramod P.
AU - Ota, Shinichi
AU - Kwak, Byung Kook
AU - Loffroy, Romaric
AU - Vali, Mustafa
PY - 2010/3/1
Y1 - 2010/3/1
N2 - 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.
AB - 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.
KW - Antiglycolytic
KW - Autophagosome
KW - ER stress
KW - Translation inhibition
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M3 - Article
C2 - 20393016
AN - SCOPUS:77951057423
SN - 0250-7005
VL - 30
SP - 923
EP - 926
JO - Anticancer Research
JF - Anticancer Research
IS - 3
ER -