Sorafenib potentiates ABT-737-induced apoptosis in human oral cancer cells. (January 2017)

• Record Type: Journal Article
• Authors: Kim, Lee-Han; Shin, Ji-Ae; Jang, Boonsil; Yang, In-Hyoung; Won, Dong-Hoon; Jeong, Joseph H.; Chung, Tae-Ho; Cho, Nam-Pyo; Cho, Sung-Dae
• Is Part Of: Archives of oral biology. Volume 73(2017)
• Page Start: 1
• Page End: 6
• Publication Date: 2017-01
• Subjects: Oral cancer -- ABT-737 -- Sorafenib -- Apoptosis -- Bax -- Bak; Mouth -- Periodicals; Mouth -- Diseases -- Periodicals; Dentistry -- Periodicals; Electronic journals; 617.6005
• DOI: 10.1016/j.archoralbio.2016.08.034
• Languages: English
• ISSNs: 0003-9969

Abstract

Highlights: Sorafenib synergistically kills oral cancer cells when combined with ABT-737. Combination treatment induces the expression of Bax and Bak and their activation. Inactivation of ERK and STAT3 may be associated with the synergy of combination treatment. Abstract: Objective: The mimetic BH3 ABT-737, a potent inhibitor of anti-apoptotic Bcl-2 family proteins, has potential as anti-cancer drug in many cancers. Recently, patients treated with ABT-737 have developed drug tolerance during cancer therapy. Therefore, we examined whether ABT-737 is effective in killing MC-3 and HSC-3 human oral cancer cells either alone or in combination with the oncogenic kinase inhibitor, sorafenib. Design: The potentiating activities of sorafenib in ABT-737-induced apoptosis were determined using trypan blue exclusion assay, DAPI staining, cell viability assay and Western blot analysis. Results: Combined use of ABT-737 and sorafenib synergistically suppressed cell viability and induced apoptosis compared with either compound individually. The combination of ABT-737 and sorafenib altered only Bax and Bak proteins and their activations, resulting in mitochondrial translocation of Bax from the cytosol. Additionally, combination treatment-mediated apoptosis may be correlated with ERK and STAT3 pathways. Conclusions: These results suggest that sorafenib may effectively overcome ABT-737 resistance to apoptotic cell death, which can be a new potential chemotherapeutic strategy against human oral cancer.