CT1 and CT3 Mediated Apoptosis of MCF7 and SKBr3 Breast Cancer Cells via Extrinsic Apoptotic Pathway

Authors' Affiliations

Autumn Locke, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Olasunkanmi Akinbote, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Jeanna Harding, 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 Magdalena Bielski, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Dewey Belcher, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Jacqueline Aramburo, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Kendra Lyndsey Hagood, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Keagan Hackworth, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City, TN. Victoria Palau, Department of Biomedical Sciences James Quillen College of Medicine, East Tennessee State University, Johnson City, TN.

Location

Culp Center Ballroom

Start Date

4-25-2023 9:00 AM

End Date

4-25-2023 11:00 AM

Poster Number

113

Faculty Sponsor’s Department

Pharmacy Practice

Name of Project's Faculty Sponsor

Victoria Palau

Classification of First Author

Pharmacy Student

Competition Type

Competitive

Type

Poster Presentation

Project's Category

Cell Lines

Abstract or Artist's Statement

Breast cancer is the second most common cancer in women in the United States, accounting for approximately 30% of newly diagnosed female cancers every year. In 2023, it is estimated that around 297,790 invasive breast cancers will be diagnosed as new cases with nearly 43,700 women deaths. The average lifetime risk of a woman in the United States accruing a breast cancer diagnosis is approximately 13%, meaning that there is a 1 in 8 chance of developing breast cancer. Classification of breast cancers is distinguished based on the presence of three receptors: HER2, estrogen, and progesterone. Absence of these receptors is categorized as triple negative breast cancer and accounts for about 15% of all breast cancers, thus is the most aggressive and difficult to treat. In this study, research involving two flavonoids, CT1 and CT3 show cytotoxic effects against cell lines MCF7 (ER+, PR+, HER2-) and SKBr3 (ER-, PR-, HER2+), that represent the most common breast cancers. CT1 and CT3 were extracted from the leaves of Chromolaena tacotana using a Soxhlet extractor, followed by isolation and purification by chromatography. The cells were seeded and then treated with CT1 or CT3 at concentrations of 5, 10, 20, 40 and 80 mM for cytotoxicity assays, and 40mM for analysis of mechanism of action via immunoblotting and TUNEL. These two flavonoids differ on the presence of a double bond between positions 2 and 3. At the concentrations tested, CT1 has cytotoxic activity against MCF7 but no significant effect on SKBr3, while CT3 has cytotoxic activity against SKBr3 but not on MCF7. CT1 and CT3 target the activated forms of ERK, c-JUN and SP6; however, the effect of CT1 appears to be significantly stronger than CT3 and does not involve the survival pathway. CT1 and CT3 inhibit cell viability in MCF7 and SKBr3 breast cancer cells by activating an extrinsic apoptotic pathway. Additional studies using a triple negative breast cancer cell line has shown that this activation is independent of the presence of estrogen and progesterone receptors or the upregulation of HER2.

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Apr 25th, 9:00 AM Apr 25th, 11:00 AM

CT1 and CT3 Mediated Apoptosis of MCF7 and SKBr3 Breast Cancer Cells via Extrinsic Apoptotic Pathway

Culp Center Ballroom

Breast cancer is the second most common cancer in women in the United States, accounting for approximately 30% of newly diagnosed female cancers every year. In 2023, it is estimated that around 297,790 invasive breast cancers will be diagnosed as new cases with nearly 43,700 women deaths. The average lifetime risk of a woman in the United States accruing a breast cancer diagnosis is approximately 13%, meaning that there is a 1 in 8 chance of developing breast cancer. Classification of breast cancers is distinguished based on the presence of three receptors: HER2, estrogen, and progesterone. Absence of these receptors is categorized as triple negative breast cancer and accounts for about 15% of all breast cancers, thus is the most aggressive and difficult to treat. In this study, research involving two flavonoids, CT1 and CT3 show cytotoxic effects against cell lines MCF7 (ER+, PR+, HER2-) and SKBr3 (ER-, PR-, HER2+), that represent the most common breast cancers. CT1 and CT3 were extracted from the leaves of Chromolaena tacotana using a Soxhlet extractor, followed by isolation and purification by chromatography. The cells were seeded and then treated with CT1 or CT3 at concentrations of 5, 10, 20, 40 and 80 mM for cytotoxicity assays, and 40mM for analysis of mechanism of action via immunoblotting and TUNEL. These two flavonoids differ on the presence of a double bond between positions 2 and 3. At the concentrations tested, CT1 has cytotoxic activity against MCF7 but no significant effect on SKBr3, while CT3 has cytotoxic activity against SKBr3 but not on MCF7. CT1 and CT3 target the activated forms of ERK, c-JUN and SP6; however, the effect of CT1 appears to be significantly stronger than CT3 and does not involve the survival pathway. CT1 and CT3 inhibit cell viability in MCF7 and SKBr3 breast cancer cells by activating an extrinsic apoptotic pathway. Additional studies using a triple negative breast cancer cell line has shown that this activation is independent of the presence of estrogen and progesterone receptors or the upregulation of HER2.