Project Title

Structurally Related Flavonoids CT1 and CT3 Have Cytotoxic Activity On Triple Negative MDA-MB-231 Breast Cancer Cells By Targeting The MEK-ERK Pathway

Authors' Affiliations

Dewey Belcher, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Keagan Hackworth, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Kendra Lyndsey Hagood, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN Jacqueline Aramburo, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Chukuwunyere Umeh, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Kristen Michaud, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Morgan Cunningham, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Garrett Mudd, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Ruben Torrenegra, Department of Chemistry, Universidad de Ciencias Aplicadas y Ambientales, Bogota, Colombia. Gina Mendez-Callejas, Department of Chemistry, Universidad de Ciencias Aplicadas y Ambientales, Bogota, Colombia. Victoria Palau, Department of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Department of Biomedical Sciences, James Quillen College of Medicine, East Tennessee State University, Johnson City, TN.

Location

Culp Ballroom

Start Date

4-7-2022 9:00 AM

End Date

4-7-2022 12:00 PM

Poster Number

32

Faculty Sponsor’s Department

Pharmaceutical Sciences

Name of Project's Faculty Sponsor

Victoria Palau

Classification of First Author

Pharmacy Student

Competition Type

Competitive

Type

Poster Presentation

Project's Category

Cancer or Carcinogenesis

Abstract or Artist's Statement

Breast cancer is the most commonly diagnosed cancer in women with an estimated 287,850 cases in 2022. Approximately 684,000 deaths each year are associated with breast cancer across the world. Risk factors of breast cancer include increased estrogen exposure, family history of breast cancer, and environmental factors. Treatment of breast cancer is highly dependent on the presence of HER2, estrogen, and progesterone receptors. Breast cancers that present with increased receptors for estrogen, progesterone, and HER2 are typically the least aggressive and the easiest to treat. The percentage of cases in the United States associated with hormone receptor positive and HER-2 negative or positive are approximately 82%. Absence of receptors for estrogen, progesterone, and HER2 is known as triple negative breast cancer. In the United States, only about 10% of cases are associated with this form. However, it is considered the most aggressive and difficult to treat. Two emerging flavonoids known as CT1 and CT3 have shown cytotoxic activity against cell lines that represent some of the most common breast cancers: MCF7, MDA-MB-231, and SKBr3. CT1 and CT3 were extracted from the leaves of Chromolaena tacotana using a Soxhlet extractor and the compounds then underwent isolation and purification. The cells were then treated with CT1 or CT3 at concentrations of 5, 10, 20, 40 and 80 µM. MTT assays were then used to determine cell viability. MDA-MB-231, the most aggressive type of breast cancer cells, responded to both CT1 and CT3. The most profound cytotoxic effects of CT1 were seen with MCF7 and MDA-MB-231, while CT3 exhibited a greater toxicity against SKBr3 cells. Preliminary results indicate that CT1 and CT3 target the MEK-ERK signaling pathway. Further studies need to be completed to determine mechanistically how these compounds lead to receptor-independent toxicity.

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Apr 7th, 9:00 AM Apr 7th, 12:00 PM

Structurally Related Flavonoids CT1 and CT3 Have Cytotoxic Activity On Triple Negative MDA-MB-231 Breast Cancer Cells By Targeting The MEK-ERK Pathway

Culp Ballroom

Breast cancer is the most commonly diagnosed cancer in women with an estimated 287,850 cases in 2022. Approximately 684,000 deaths each year are associated with breast cancer across the world. Risk factors of breast cancer include increased estrogen exposure, family history of breast cancer, and environmental factors. Treatment of breast cancer is highly dependent on the presence of HER2, estrogen, and progesterone receptors. Breast cancers that present with increased receptors for estrogen, progesterone, and HER2 are typically the least aggressive and the easiest to treat. The percentage of cases in the United States associated with hormone receptor positive and HER-2 negative or positive are approximately 82%. Absence of receptors for estrogen, progesterone, and HER2 is known as triple negative breast cancer. In the United States, only about 10% of cases are associated with this form. However, it is considered the most aggressive and difficult to treat. Two emerging flavonoids known as CT1 and CT3 have shown cytotoxic activity against cell lines that represent some of the most common breast cancers: MCF7, MDA-MB-231, and SKBr3. CT1 and CT3 were extracted from the leaves of Chromolaena tacotana using a Soxhlet extractor and the compounds then underwent isolation and purification. The cells were then treated with CT1 or CT3 at concentrations of 5, 10, 20, 40 and 80 µM. MTT assays were then used to determine cell viability. MDA-MB-231, the most aggressive type of breast cancer cells, responded to both CT1 and CT3. The most profound cytotoxic effects of CT1 were seen with MCF7 and MDA-MB-231, while CT3 exhibited a greater toxicity against SKBr3 cells. Preliminary results indicate that CT1 and CT3 target the MEK-ERK signaling pathway. Further studies need to be completed to determine mechanistically how these compounds lead to receptor-independent toxicity.