HERG K+ channel related chemosensitivity to sparfloxacin in colon cancer cells

Abstract

Abstract. Potassium channels are essential for the regulation of cell proliferation. As reported, HERG protein is overexpressed in a wide range of human tumors, including colon carcinoma. The aim of this study was to investigate the effects of antibacterial agents sparfloxacin (SPFX), a blocker of HERG channel, on HERG K + channel highly expressing colon cancer cells. Expression of HERG and apoptosis correlative proteins was examined by Western blotting. The MTT assay was used to detect the cytotoxicity of drugs and drug combination in vitro. Gene transfection was used to examine the changes in herg-related chemosensitivity. Cell apoptosis was analyzed by flow cytometry. The migration and invasion capacity of tumor cells by SPFX was determined by gelatin zymography assay and Boyden chamber. The in vivo efficacy of SPFX was assessed in murine colon carcinoma C26 in BALB/c mice and human colon carcinoma HCT116 xenografts in nude mice. High expression of HERG protein was detected in colon cancer C26, HCT116 and HT-29 cells. The cell viability of the colon cancer cells was inhibited by SPFX in a dosedependent manner. SPFX induced apoptosis and inhibited migration and invasion of colon cancer HCT116 cells. The increase in apoptosis was associated with a decrease in procaspase-3 and Bcl-2 protein expression. Study with hergtransfected HEK293 cells and siRNA-knock down HCT116 cells confirmed that the cell viability inhibition by SPFX was correlated with HERG expression. When combined with 5-fluorouracil, SPFX showed synergistic anti-proliferation activity in HCT116 and HT-29 cells. Furthermore, SPFX inhibited the growth of human colon carcinoma HCT116 xenografts and showed synergistic effect with 5-fluorouracil in vivo. Our finding suggested that SPFX could be a biochemical modulator in treatment of colon cancer with chemotherapeutic drugs.

Fluoroquinolones Suppress TGF-β and PMA-Induced MMP-9 Production in Cancer Cells: Implications in Repurposing Quinolone Antibiotics for Cancer Treatment

“…Previous and current studies demonstrate an effect of FQs on the expression level of MMP-9 [15], suggesting that FQs could be a potential therapeutic agent for ameliorating cancer development and dissemination. We also revealed that FQ inhibits MMP-9 expression via p38 and cAMP-dependent pathways in TGF-β-and PMA-stimulated A549 cells.…”

“…FQs also display non-canonical mechanisms of action including, but not limited to, immunomodulatory and antitumor properties. Sparfloxacin was shown to suppress MMP-9 production by blocking HERG channel [15]. Additionally, by affecting p21/p27/p53 activities, gatifloxacin was also found to synergize the effect of gemcitabine, cisplatin as well as the broad-spectrum anticancer drugs against pancreatic cancer [16].…”

MicroRNA 362-3p Reduces hERG-related Current and Inhibits Breast Cancer Cells Proliferation

“…The hERG gene is expressed in certain cancers and has been associated with cancer development and progression (2,25). Furthermore, inhibition of the hERGrelated potassium channel has been shown to impair cell proliferation and the invasiveness of tumor cells including colorectal cancer, glioma, breast cancer, and leukemias (11)(12)(13)(14)(26)(27)(28). In this study, we identified miR-362-3p as a potential regulator of hERG expression and function in breast cancer cells.…”

Хемосенсибилизация Опухолевых Клеток Фенольными Антиоксидантами: Роль Фактора Транскрипции Nrf2

“…Показано, что противоопухолевые свойства куркумина реализуются с участием АФК [122,123]. Предполагается, что куркумин вызывает АФК-индуцируемое снижение трансмембранного митохондриального потенциала, в результате активируется апоптоз [124,125]. В ряде работ показана способность куркумина через усиление внутриклеточной продукции АФК активировать аутофагию, при этом антиоксидант N-ацетилцистеин снижал, а пероксид водорода усиливал аутофагию [126,127].…”