Abstract
Extensive data from both in vitro and animal studies have demonstrated the potency of a deregulated activated Wnt pathway. Herein, we report the antitumor effects of already established novel Wnt pathway inhibitors – ethacrynic acid (EA) and Ciclopiroxolamine (CIC) on various cancer cell lines using the WST-8 assay. Our results demonstrate the significant cytotoxic potency of EA and CIC in vitro and display their strong efficacy on various tumor cells. Of particular interest, colon cancer was the most significantly affected by both drugs of all the tumor types tested in this study. This study provides a strategy for targeting Wnt-driven cancers and highlights those cancers that show a higher susceptibility to the cytotoxic effects of the Wnt inhibitors as potential candidates for further study.
Highlights
The challenge in cancer management worldwide, despite significant progress in therapy and remission rates, has propelled research to establish the therapeutic relevance of cancer stem cells (CSCs) as they play a key role in drug resistance, progression and recurrence of several cancers
The pancreatic cancer cell line DanG; prostate cancer cell line DU145 and ovarian cancer cell line A278003 were cultured in 50 % Roswell Park Memorial Institute (RPMI) medium (PAN Biotech, Aidenbach, Germany) supplemented with 50% heat inactivated fetal calf serum (FCS) (Gibco Life Technologies, Darmstadt, Germany) and 1% penicillin / streptomycin (P/S) (Life Technologies, Darmstadt, Germany)
The melanoma cancer cell line HT-144, breast cancer cell line SKBR-3, and bladder cancer cell line T24 were cultured in 50% McCoy medium supplemented with 50% FCS plus 1% P/S
Summary
The challenge in cancer management worldwide, despite significant progress in therapy and remission rates, has propelled research to establish the therapeutic relevance of cancer stem cells (CSCs) as they play a key role in drug resistance, progression and recurrence of several cancers. Research interests and efforts are currently geared towards targeting CSCs as a panacea to the menace. Most current anti-cancer drugs, small molecule inhibitors and monoclonal antibodies (mAbs), are designed to target rapidly proliferating cells which represent committed cancer cells but not CSC[3]. Since current cancer therapies fail to eradicate CSCs, the goal of current cancer therapeutics research is focused on targeted therapies in combination with standard chemotherapies. A selective targeting of the Wnt signaling pathway has been considered a promising strategic advantage for therapy as several preclinical experiments have demonstrated that inhibition of this pathway would diminish cancer stem cell pool and eradicate cancer
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