Date of Award

2024

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. A.R.M.Ruhul Amin, CommitteeChairperson

Second Advisor

Dr. Melinda Varney

Third Advisor

Dr.Jeremy McAleer

Abstract

Chemotherapy poses a significant challenge for cancer patients due to drug-associated toxicity, which often results from their effects on both healthy (normal) and cancerous cells. While various options aim to reduce toxicity and optimize beneficial effects, a comprehensive solution remains elusive. Cyclotherapy is one such approach developed to protect normal cells from the toxic effects of chemotherapy drugs. The basic principle underlying cyclotherapy is p53- dependent cell cycle arrest of normal cells while killing cancer cells via a p53-independent mechanism using a second drug. In our research, we investigated the inhibitory effects of a combination of two low-dose anticancer drugs, Actinomycin D and Resveratrol, in Aerodigestive tract cancers, which are a leading cause of cancer-related deaths in the United States and globally. p21 plays the central role in p53-dependent cell cycle arrest. Utilizing an advanced technique, digital droplet polymerase chain reaction, we observed a synergistic increase in the expression of p21 mRNA when Actinomycin D and Resveratrol were used in combination. Furthermore, we elucidated the mechanism of cell death induced by the combination of Actinomycin D and Resveratrol by identifying proteins such as p53, PUMA, ATF3, and GDF15. These findings offer valuable insights for the development of future chemotherapeutic combinations involving Actinomycin D and Resveratrol, with the potential to improve cancer management.

Subject(s)

Cancer -- Chemotherapy.

Dactinomycin.

Resveratrol -- Health aspects.

Cancer -- Treatment.

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