Title

Heme Oxygenase 1 as a Cytotoxic Target for a Novel Isoflavone, ME-344

School Name

South Carolina Governor's School for Science & Mathematics

Grade Level

12th Grade

Presentation Topic

Biochemistry

Presentation Type

Mentored

Oral Presentation Award

2nd Place

Abstract

ME-344 is an anticancer drug in phase-1 clinical trials that inhibits mitochondrial oxidative phosphorylation, making it a candidate treatment for cancer stem cells. Researchers must determine ME-344’s mechanism of action (MOA) to ensure the safety and effectiveness of ME-344 treatment. Previous research suggests heme-oxygenase 1(HO-1) is ME-344’s cytotoxic target. This research was conducted to verify that result. HO-1 was knocked down in five cell lines, with a sixth used as a nontarget. Next, an MTT assay was performed to construct a viability curve and extrapolate the IC50 values for each cell line. Finally, a western blot was then performed on an SDS-PAGE run on proteins harvested from two groups of cell lysates: a control group and an experimental group treated with the respective IC50 of each cell line. The MTT assays showed the IC50s of the HO-1 knockdown cell lines were 5-10 times lower than the nontarget. The western blot for the control groups showed HO-1 expression in the knockdown cell lines was 47%-82% lower than the nontarget. There were no western blot results for the experimental groups because not enough protein was collected from the lysates. The change in the cytotoxic profile in the HO-1 knockdown cell lines compared to the nontarget indicates HO-1 is a target of ME-344. Fewer steps remain undetermined in ME-344’s MOA. Determining these will enable clinicians to conduct safer treatments and to test ME-344 in conjunction with other treatments.

Location

Founders Hall 111 A

Start Date

3-30-2019 10:45 AM

Presentation Format

Oral Only

Group Project

No

COinS
 
Mar 30th, 10:45 AM

Heme Oxygenase 1 as a Cytotoxic Target for a Novel Isoflavone, ME-344

Founders Hall 111 A

ME-344 is an anticancer drug in phase-1 clinical trials that inhibits mitochondrial oxidative phosphorylation, making it a candidate treatment for cancer stem cells. Researchers must determine ME-344’s mechanism of action (MOA) to ensure the safety and effectiveness of ME-344 treatment. Previous research suggests heme-oxygenase 1(HO-1) is ME-344’s cytotoxic target. This research was conducted to verify that result. HO-1 was knocked down in five cell lines, with a sixth used as a nontarget. Next, an MTT assay was performed to construct a viability curve and extrapolate the IC50 values for each cell line. Finally, a western blot was then performed on an SDS-PAGE run on proteins harvested from two groups of cell lysates: a control group and an experimental group treated with the respective IC50 of each cell line. The MTT assays showed the IC50s of the HO-1 knockdown cell lines were 5-10 times lower than the nontarget. The western blot for the control groups showed HO-1 expression in the knockdown cell lines was 47%-82% lower than the nontarget. There were no western blot results for the experimental groups because not enough protein was collected from the lysates. The change in the cytotoxic profile in the HO-1 knockdown cell lines compared to the nontarget indicates HO-1 is a target of ME-344. Fewer steps remain undetermined in ME-344’s MOA. Determining these will enable clinicians to conduct safer treatments and to test ME-344 in conjunction with other treatments.