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Bromoethylindole (BEI-9) redirects NF-?B signaling induced by camptothecin and TNF? to promote cell death in colon cancer cells.

ABSTRACT: Chemotherapeutic regimens containing camptothecin (CPT), 5-fluorouracil, and oxaliplatin are used to treat advanced colorectal cancer. We previously reported that an indole derivative, 3-(2-bromoethyl)indole (BEI-9), inhibited the proliferation of colon cancer cells and suppressed NF-?B activation. Here, we show that a combination of BEI-9 with either CPT or tumor necrosis factor alpha (TNF?) enhances cell death. Using colorectal cancer cells, we examined the activation of NF-?B by drugs, the potential of BEI-9 for inhibiting drug-induced NF-?B activation, and the enhancement of cell death by combination treatments. Cells were treated with the chemotherapeutic drugs alone or in combination with BEI-9. NF-?B activation, cell cycle profiles, DNA-damage response, markers of cell death signaling and targets of NF-?B were evaluated to determine the effects of single and co-treatments. The combination of BEI-9 with CPT or TNF? inhibited NF-?B activation and reduced the expression of NF-?B-responsive genes, Bcl-xL and COX2. Compared to CPT or BEI-9 alone, sequential treatment of the cells with CPT and BEI-9 significantly enhanced caspase activation and cell death. Co-treatment with TNF? and BEI-9 also caused more cytotoxicity than TNF? or BEI-9 alone. Combined BEI-9 and TNF? enhanced cell death through caspase activation and cleavage of the switch-protein, RIP1 kinase. BEI-9 reduced the expression of COX2 both alone and in combination with CPT or TNF. We postulate that BEI-9 enhances the effects of these drugs on cancer cells by turning off or redirecting NF-?B signaling. Therefore, the combination of BEI-9 with drugs that activate NF-?B needs to be evaluated for clinical applications.

SUBMITTER: Chowdhury R

PROVIDER: S-EPMC6005376 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Bromoethylindole (BEI-9) redirects NF-κB signaling induced by camptothecin and TNFα to promote cell death in colon cancer cells.

Chowdhury Rupak R Gales Dominique D Valenzuela Paloma P Miller Sonni S Yehualaeshet Teshome T Manne Upender U Francia Giulio G Samuel Temesgen T

Apoptosis : an international journal on programmed cell death 20171201 12

Chemotherapeutic regimens containing camptothecin (CPT), 5-fluorouracil, and oxaliplatin are used to treat advanced colorectal cancer. We previously reported that an indole derivative, 3-(2-bromoethyl)indole (BEI-9), inhibited the proliferation of colon cancer cells and suppressed NF-κB activation. Here, we show that a combination of BEI-9 with either CPT or tumor necrosis factor alpha (TNFα) enhances cell death. Using colorectal cancer cells, we examined the activation of NF-κB by drugs, the po ...[more]

PMID: 29116428

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Dataset Information

Bromoethylindole (BEI-9) redirects NF-?B signaling induced by camptothecin and TNF? to promote cell death in colon cancer cells.

Publications

Bromoethylindole (BEI-9) redirects NF-κB signaling induced by camptothecin and TNFα to promote cell death in colon cancer cells.

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