title: Combination treatment with arsenic trioxide and sulindac augments their apoptotic potential in lung cancer cells through activation of caspase cascade and mitochondrial dysfunction.
abstract: Non-steroidal anti-inflammatory drugs (NSAIDs) are known to enhance the responsiveness of tumor cells toward chemotherapeutic drugs and radiation. However, the precise mechanism of synergistic enhancement in tumoricidal activity is not clearly known. Herein, we demonstrate that the combination treatment of arsenic trioxide (As2O3) and sulindac resulted in a synergistic augmentation of cytotoxicity toward NCI-H157 lung cancer cells, which was revealed as apoptosis accompanied by chromatin fragmentation and an increase in sub-G0/G1 fraction. In addition, combination treatment with As2O3 and sulindac increased the catalytic activity of caspase-3, -8, and -9 along with induction of Fas/FasL expression and cytosolic release of cytochrome c. Pharmacologic scavenging study of reactive oxygen species (ROS) revealed that synergistic augmentation of cytotoxicity was achieved by generation of ROS, which might modulate the expression of Bcl-2 family proteins, the activity of caspase-3, and mitochondrial membrane potential transition.
authors: Department of Internal Medicine, Wonkwang University, School of Medicine, Jeonbuk 570-749, South Korea.
authors: Hak-Ryul
authors: HR
authors: Kim
authors: Eun-Jung
authors: EJ
authors: Kim
authors: Sei-Hoon
authors: SH
authors: Yang
authors: Eun-Taik
authors: ET
authors: Jeong
authors: Channy
authors: C
authors: Park
authors: Se-Jin
authors: SJ
authors: Kim
authors: Myung-Ja
authors: MJ
authors: Youn
authors: Hong-Seob
authors: HS
authors: So
authors: Raekil
authors: R
authors: Park