Tomoya Takenaka1,2, Miku Katayama1,2, Ayaka Sugiyama1,2, Masaya Hagiwara1, Ikuo Fujii2, Tomoka Takatani-Nakase3, Susumu S Kobayashi4, Ikuhiko Nakase5. 1. NanoSquare Research Institution, Research Center for the 21st Century, Organization for Research Promotion, Osaka Prefecture University, Sakai, Japan. 2. Graduate School of Science, Osaka Prefecture University, Osaka, Japan. 3. Department of Pharmaceutics, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Nishinomiya, Japan. 4. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, U.S.A. skobayas@bidmc.harvard.edu i-nakase@21c.osakafu-u.ac.jp. 5. NanoSquare Research Institution, Research Center for the 21st Century, Organization for Research Promotion, Osaka Prefecture University, Sakai, Japan skobayas@bidmc.harvard.edu i-nakase@21c.osakafu-u.ac.jp.
Abstract
BACKGROUND/AIM: Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and has been approved for the treatment of non-small cell lung cancers (NSCLCs) with EGFR mutations. Here we demonstrated that gefitinib induced a significantly enhanced biological activity of succinate-tetrazolium reductase (STR) in mitochondria and mitochondrial membrane potential in HCC827 cells (EGFR mutation NSCLCs, sensitive to gefitinib) at a high cell density. MATERIALS AND METHODS: We assessed the biological activity (STR, mitochondrial membrane potential, expression level of Bcl-2 family proteins) of gefitinib on NSCLCs at different cell densities. RESULTS: The 3D cell culture experiments showed the enhanced mitochondrial biological activity in clustered cell culture treated with gefitinib. Interestingly, the expression levels of Bcl-xL and Bax, were affected by the cellular number and gefitinib treatment. We also found that gefitinib prevented additive anticancer activity in the combinational treatment with doxorubicin, which induces mitochondria-dependent apoptotic cell death. CONCLUSION: Our results indicate that gefitinib may work as a mitochondrial protector against combinational treatment with mitochondria-dependent anticancer agents in high-cell-density. Copyright
BACKGROUND/AIM: Gefitinib is a tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and has been approved for the treatment of non-small cell lung cancers (NSCLCs) with EGFR mutations. Here we demonstrated that gefitinib induced a significantly enhanced biological activity of succinate-tetrazolium reductase (STR) in mitochondria and mitochondrial membrane potential in HCC827 cells (EGFR mutation NSCLCs, sensitive to gefitinib) at a high cell density. MATERIALS AND METHODS: We assessed the biological activity (STR, mitochondrial membrane potential, expression level of Bcl-2 family proteins) of gefitinib on NSCLCs at different cell densities. RESULTS: The 3D cell culture experiments showed the enhanced mitochondrial biological activity in clustered cell culture treated with gefitinib. Interestingly, the expression levels of Bcl-xL and Bax, were affected by the cellular number and gefitinib treatment. We also found that gefitinib prevented additive anticancer activity in the combinational treatment with doxorubicin, which induces mitochondria-dependent apoptotic cell death. CONCLUSION: Our results indicate that gefitinib may work as a mitochondrial protector against combinational treatment with mitochondria-dependent anticancer agents in high-cell-density. Copyright
Authors: Yanqi Xie; Wen Zhang; Lichao Guo; Liliia M Kril; Kristin L Begley; Vitaliy M Sviripa; Xi Chen; Xifu Liu; Eun Y Lee; Daheng He; Chi Wang; Tianyan Gao; Xiaoqi Liu; B Mark Evers; David S Watt; Chunming Liu Journal: Mol Cancer Ther Date: 2021-08-10 Impact factor: 6.261