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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