Project Title

Additional Hydroxyl group on CT6 (3,4-dihydroxy-5,7-dimethoxyflavone), a flavone extracted from Chromolaena Tacotana potentially confers additional activity against pancreatic cancer as compared to CT7 (4-hydroxy-5,7-dimethoxyflavone)

Authors' Affiliations

Parker Wade, Department of Pharmaceutical Sciences, College of Pharmacy, East Tennessee State University, Johnson City, TN. Miranda Green, Department of Pharmaceutical Sciences, College of Pharmacy, East Tennessee State University, Johnson City, TN. April Weaver, Department of Pharmaceutical Sciences, College of Pharmacy, East Tennessee State University, Johnson City, TN. Omri Coke, Department of Pharmaceutical Sciences, College of Pharmacy, East Tennessee State University, Johnson City, TN. Ruben D. Torrenegra, Department of Chemistry, Universidad de Ciencias Aplicadas y Ambientales, Bogota, Colombia Victoria Palau, Department of Pharmaceutical Sciences, College of Pharmacy, East Tennessee State University, Johnson City, TN.

Location

Clinch Mtn

Start Date

4-12-2019 9:00 AM

End Date

4-12-2019 2:30 PM

Poster Number

175

Faculty Sponsor’s Department

Pharmaceutical Sciences

Name of Project's Faculty Sponsor

Dr. Victoria Palau

Type

Poster: Competitive

Classification of First Author

Pharmacy Student

Project's Category

Cell Lines, Cancer or Carcinogenesis

Abstract Text

Additional Hydroxyl group on CT6 (3,4-dihydroxy-5,7-dimethoxyflavone), a flavone extracted from Chromolaena Tacotana potentially confers additional activity against pancreatic cancer as compared to CT7 (4-hydroxy-5,7-dimethoxyflavone)

Parker Wade1, Miranda Green1, April Weaver1, Omri Coke1, Ruben D. Torrenegra2, and Victoria Palau1

1Department of Pharmaceutical Sciences, College of Pharmacy, East Tennessee State University, Johnson City, TN.

2Department of Chemistry, Universidad de Ciencias Aplicadas y Ambientales, Bogota, Colombia and

Pancreatic cancer is one of the deadliest types of cancers, with a mortality rate of about 95%. This high mortality rate signifies there is a need for further research into finding treatment options for those affected by pancreatic cancer. Recent studies have found cytotoxic effects on cancerous cells elicited from compounds, such as flavones, in plants indigenous to Western South America, specifically Colombia. The flavones 3,4-dihydroxy-5,7-dimethoxyflavone (CT6) and 4-hydroxy-5,7-dimethoxyflavone (CT7) were isolated from Chromolaena Tacotana, member of the asteraceae family. The molecular structures of the flavones differ only by an additional hydroxyl group on CT6. Both of these compounds were tested on MIA PaCa2 and Panc28 pancreatic cancer cells at concentrations ranging from 5μM to 80μM. Cell viability after dosing of CT6 and CT7 was determined using MTT and spectrophotometry analysis. MIA PaCa2 is more poorly differentiated than Panc28. CT6 conferred greater activity on both cell lines compared to CT7. Percent cell viability of the Panc28 cell line reached a low of 35.55% (p=0.0001) with CT6, compared to 84.25% (p=0.0275) with CT7. Percent cell viability of the MIA PaCa2 cell line reached a low of 46.72% (p=0.000001)with CT6. However, CT7 showed no significant difference, with percent cell viability reaching 103.73% (p=0.5605) when compared to the control for this cell line. While CT6 exerted cytotoxic activity on both Panc28 and MIA PaCa2, CT6 had significantly more cytotoxic activity on Panc28, which could be related to the greater differentiation status of this cell line. More in depth studies will need to be conducted to determine the exact reasons for greater activity of CT6 on Panc28 cells. This could be due to the compound’s target, mitochondrial activity of the cell lines, and the minor structural differences between the two compounds.

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Apr 12th, 9:00 AM Apr 12th, 2:30 PM

Additional Hydroxyl group on CT6 (3,4-dihydroxy-5,7-dimethoxyflavone), a flavone extracted from Chromolaena Tacotana potentially confers additional activity against pancreatic cancer as compared to CT7 (4-hydroxy-5,7-dimethoxyflavone)

Clinch Mtn

Additional Hydroxyl group on CT6 (3,4-dihydroxy-5,7-dimethoxyflavone), a flavone extracted from Chromolaena Tacotana potentially confers additional activity against pancreatic cancer as compared to CT7 (4-hydroxy-5,7-dimethoxyflavone)

Parker Wade1, Miranda Green1, April Weaver1, Omri Coke1, Ruben D. Torrenegra2, and Victoria Palau1

1Department of Pharmaceutical Sciences, College of Pharmacy, East Tennessee State University, Johnson City, TN.

2Department of Chemistry, Universidad de Ciencias Aplicadas y Ambientales, Bogota, Colombia and

Pancreatic cancer is one of the deadliest types of cancers, with a mortality rate of about 95%. This high mortality rate signifies there is a need for further research into finding treatment options for those affected by pancreatic cancer. Recent studies have found cytotoxic effects on cancerous cells elicited from compounds, such as flavones, in plants indigenous to Western South America, specifically Colombia. The flavones 3,4-dihydroxy-5,7-dimethoxyflavone (CT6) and 4-hydroxy-5,7-dimethoxyflavone (CT7) were isolated from Chromolaena Tacotana, member of the asteraceae family. The molecular structures of the flavones differ only by an additional hydroxyl group on CT6. Both of these compounds were tested on MIA PaCa2 and Panc28 pancreatic cancer cells at concentrations ranging from 5μM to 80μM. Cell viability after dosing of CT6 and CT7 was determined using MTT and spectrophotometry analysis. MIA PaCa2 is more poorly differentiated than Panc28. CT6 conferred greater activity on both cell lines compared to CT7. Percent cell viability of the Panc28 cell line reached a low of 35.55% (p=0.0001) with CT6, compared to 84.25% (p=0.0275) with CT7. Percent cell viability of the MIA PaCa2 cell line reached a low of 46.72% (p=0.000001)with CT6. However, CT7 showed no significant difference, with percent cell viability reaching 103.73% (p=0.5605) when compared to the control for this cell line. While CT6 exerted cytotoxic activity on both Panc28 and MIA PaCa2, CT6 had significantly more cytotoxic activity on Panc28, which could be related to the greater differentiation status of this cell line. More in depth studies will need to be conducted to determine the exact reasons for greater activity of CT6 on Panc28 cells. This could be due to the compound’s target, mitochondrial activity of the cell lines, and the minor structural differences between the two compounds.