"Investigating the effects of BAG3 knockdown on the cytotoxicity of the" by Kayla Gross

Date of Award

2013

Document Type

Honors Thesis (Open Access)

Department

Colby College. Chemistry Dept.

Advisor(s)

Kevin P. Rice

Second Advisor

Ethan Kohn

Abstract

Laromustine is a sulfonylhydrazine anticancer prodrug whose cytotoxicity results from the formation of interstrand cross-links caused by the synergistic action of co- generated 2-chloroethylating and carbamoylating species. The cytotoxic activities of Laromustine involve the induction of apoptosis. Described herein is an investigation into this drug’s effects on apoptotic gene expression in HL-60 cells using qRT-PCR. Significant changes in the expression levels of 13 genes were observed, most dramatically in the upregulation of the bcl2-associated athanogene 3 (BAG3) gene. Given the pro-survival role of BAG3 in the cell, this investigation sought to decrease BAG3 mRNA levels in HL-60 cells using transient shRNA transfections in conjunction with qRT-PCR analysis and cell death assays to assess the effect of BAG3 knockdown on sensitizing cancerous cells to Laromustine-induced cell death.

Keywords

BAG3, Laromustine, Leukemia, Apoptosis

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Biochemistry Commons

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