Antibiotic monensin synergizes with EGFR inhibitors and oxaliplatin to suppress the proliferation of human ovarian cancer cells

Abstract

Ovarian cancer is the most lethal gynecologic malignancy with an overall cure rate of merely 30%. Most patients experience recurrence within 12–24 months of cure and die of progressively chemotherapy-resistant disease. Thus, more effective anti-ovarian cancer therapies are needed. Here, we investigate the possibility of repurposing antibiotic monensin as an anti-ovarian cancer agent. We demonstrate that monensin effectively inhibits cell proliferation, migration and cell cycle progression, and induces apoptosis of human ovarian cancer cells. Monensin suppresses multiple cancer-related pathways including Elk1/SRF, AP1, NFκB and STAT, and reduces EGFR expression in ovarian cancer cells. Monensin acts synergistically with EGFR inhibitors and oxaliplatin to inhibit cell proliferation and induce apoptosis of ovarian cancer cells. Xenograft studies confirm that monensin effectively inhibits tumor growth by suppressing cell proliferation through targeting EGFR signaling. Our results suggest monensin may be repurposed as an anti-ovarian cancer agent although further preclinical and clinical studies are needed.

A Blockade of IGF Signaling Sensitizes Human Ovarian Cancer Cells to the Anthelmintic Niclosamide-Induced Anti-Proliferative and Anticancer Activities

“…The 12 cancerrelate signaling pathway GLuc reporters were homemade and previously described [61], including NFAT, HIF-1, TCF/LEF, E2F/DP1, Elk1/SRF, AP1, NFκB, Smad, STAT1/2, RBP-Jκ, CREB, Myc/Max reporters. A constitutively active reporter pG2Luc was used as a control [18,63]. Experimentally, subconfluent SKOV3 cells were seeded in 25 cm 2 culture flasks and transfected with 3.0µg per flask of the 13 reporter plasmids using Lipofectamine (Invitrogen).…”

Engineering the Rapid Adenovirus Production and Amplification (RAPA) Cell Line to Expedite the Generation of Recombinant Adenoviruses

“…The iMEF cells are mouse mesenchymal stem cells (MSCs) previously described [17, 18]. These cells lines were maintained in Dulbecco’s Modified Eagle Medium (DMEM) supplemented with 10% fetal bovine serum (FBS, Hyclone, Logan, UT, USA), 100 units/ml penicillin, and 100 g/ml streptomycin at 37°C in 5% CO 2 as described [19, 20]. Unless indicated otherwise, all other reagents were purchased from Sigma-Aldrich (St. Louis, MO) or Thermo Fisher Scientific (Waltham, MA).…”

“…Gaussia luciferase assay was carried out as previously described [19, 33-35]. Briefly, 50µl culture medium of the adenovirus-infected cells was taken and mixed with 20µl of the BioLux Gaussia Luciferase Flex Assay Kit (New England Biolabs) for bioluminescence measurement.…”

Niclosamide Exhibits Potent Anticancer Activity and Synergizes with Sorafenib in Human Renal Cell Cancer Cells

“…At 72h after treatment, cells were washed with PBS and stained with 0.5% crystal violet/formalin solution at room temperature for 20-30min. The stained cells were rinsed with tape water and air dried for taking macrographic images [18]. For quantitative measurement, the stained cells were dissolved in 10% acetic acid at room temperature for 20min, followed by measuring absorbance at 570-590nm [22].…”

“…Niclosamide (trade name Niclocide), a teniacide in the anthelmintic family, has been approved for human use for nearly 50 years. Niclosamide was thought to inhibit oxidative phosphorylation and stimulates ATPase activity in the mitochondria of cestodes of tapeworm, killing the scolex and proximal segments of the tapeworm, which is well tolerated in humans [18,19]. Through various high-throughput screening campaigns, Niclosamide was identified as a potential anticancer agent [19], and showed effective anticancer activity in several types of human cancer [20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39].…”