Int J Oncol. 2014 Jun;44(6):2016-24. doi: 10.3892/ijo.2014.2361. Epub 2014 Mar 27.
Antibody ligation of CM1 on cisplatin-exposed HeLa cells induces apoptosis through reactive oxygen species-dependent Fas ligand expression.
Park GB1, Kim D1, Yoon HS1, Kim YS1, Lee HK2, Kim KT3, Jeong DH3, Hur DY3.
Department of Anatomy and Research Center for Woman Disease, Inje University College of Medicine, Busan 614-735, Republic of Korea.
Department of Internal Medicine, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
Department of Obstetrics and Gynecology, Inje University Busan Paik Hospital, Busan 614-735, Republic of Korea.
Centrocyte/centroblast marker 1 (CM1) has been identified as a pro-apoptosis molecule on B-cell lymphoma cells as well as several types of cancer cells. In this study, we investigated its signaling mechanism in HeLa cells after treatment with cisplatin in order to potentially identify a new therapeutic target. The CM1 molecule was induced on the surface of cisplatin-exposed HeLa cells. In these cells, ligation of CM1 with anti-CM1 monoclonal antibodies inhibited cell proliferation and produced reactive oxygen species. Fas ligand (FasL) expression was upregulated without upregulating Fas in cisplatin-exposed HeLa cells after CM1 stimulation. Pretreatment with N-acetylcysteine, a pan-capase inhibitor, and ZB4, an antagonistic anti-Fas antibody, effectively inhibited the apoptotic effect triggered by CM1. CM1 ligation induced apoptosis through disruption of the mitochondrial membrane potential, decreased Bcl-2 and phosphorylated ERK expression. These findings identify CM1 as a potential new therapeutic target related to cisplatin-exposed cervical cancer.