Jump to main content
Jump to site search


Phenylarsine oxide (PAO) induces apoptosis in HepG2 cells via ROS-mediated mitochondria and ER-stress dependent signaling pathways.

Abstract

Arsenic Trioxide (As2O3) is an old drug that has recently been re-introduced as a therapeutic agent for acute promyelocytic leukemia (APL). Although As2O3 is also applied to treat other types of cancers in vitro and in vivo, it has been reported that single agent As2O3 has poor efficacy against non-hematologic malignant cancers in clinical trials. Recently, a few reports indicate that organic arsenic compounds can be a possible alternative for the treatment of As2O3-resistance cancers. In this study, we aimed to investigate whether the organic arsenic compound phenylarsine oxide (PAO) has potent cytotoxic effect againsthuman hepatocellular carcinoma (HCC) HepG2 cells. Our results showed that PAO not only had potent inhibitory effect on the proliferation of HepG2 cells, but also activated apoptosis-related proteins (e.g., caspase-3 and -9 and poly-ADP ribose polymerase) in a dose- and time-dependent manner. Furthermore, intracellular ROS was specifically accumulated in mitochondria and endoplasmic reticulum (ER) after exposure to PAO, implying that they are the target organelles for PAO-induced cytotoxicity. Additionally, when cells were pretreated with antioxidant N-acetylcysteine (NAC), apoptosis and ER-stress were attenuated significantly, suggesting that induction of apoptosis and cell death probably occurs through the ROS-mediated mitochondria and ER-stress dependent signaling pathways.

Back to tab navigation

Publication details

The article was received on 12 Jun 2017, accepted on 03 Aug 2017 and first published on 03 Aug 2017


Article type: Paper
DOI: 10.1039/C7MT00179G
Citation: Metallomics, 2017, Accepted Manuscript
  •   Request permissions

    Phenylarsine oxide (PAO) induces apoptosis in HepG2 cells via ROS-mediated mitochondria and ER-stress dependent signaling pathways.

    P. Huang, Y. H. Zhang, X. W. Zheng, Y. J. Liu, H. Zhang, L. Fang, Y. W. Zhang, C. Yang, K. Islam, C. Wang and H. Naranmandura, Metallomics, 2017, Accepted Manuscript , DOI: 10.1039/C7MT00179G

Search articles by author

Spotlight

Advertisements