Janset Anzour

Conference 2024 Poster

Poster Title

Therapeutic Efficacy of 5-Fluorouracil in Combination with Baicalein against Colorectal Cancer

Authors and Affiliations

Janset S. Anzour1, Marwan Emara 1
1 Center for Aging and Associated Diseases, Zewail City of Sciences and Technology, Giza, Egypt

Abstract

Background

Colorectal cancer (CRC) is the most common gastrointestinal malignancy with a higher incidence and mortality rate worldwide. Although 5-fluorouracil (5-FU) is the first-line drug for the metastatic stage, its systemic toxicity, poor response, and unpredictable resistance represent major obstacles against effective treatment. Combining cytotoxic chemotherapy with phytochemicals could enhance its anti-cancer effect while reducing its dose. This study aims to evaluate the growth inhibition of baicalein individually and conjointly with the chemotherapeutic 5FU against CRC.

Methods

MTT assay was used to detect the proliferation of two cancer cell lines: (HCT-116) and (RKO) treated with different concentration of 5FU, Baicalein and their combination. Drugs interactions were evaluated with the combination index (CI) method. Flow cytometry was employed to determine both apoptosis using Annexin V /propidium iodide (PI) assay and Cell cycle analysis using PI. Finally, the cellular migration was detected by wound healing assay.

Results

MTT assay demonstrated that baicalein inhibited the proliferation of cancer cells dose-dependently after 24 and 48 h while 5FU exhibited effective cytotoxic effects after 48 h. The Combination index (CI) indicated a remarkable synergistic effect of 5FU and baicalein after 48 h. The half-maximal inhibitory concentration (IC50) of 5-FU was lowered significantly from 19 µM to 12.85 µM in HCT-116. Similarly, it was reduced from 28 µM to 11.17 µM in RKO. Annexin V/PI assay using flow cytometry detected that combination therapy achieved higher apoptotic percentages than the single agent 5-FU with 53.21% in HCT-116 and 21.2% in RKO. Cell cycle analysis revealed that baicalein with 5FU had increased the amount of pre G1 phase leading consequently to an arrest at G2/M and G1/S in HCT-116 and RKO respectively. Moreover, Baicalein significantly reduced the wound closure from 67.5% in 19 μM 5FU and 41% in 28 μM 5FU to 34.2% and 16.2% in baicalein-5FU combination in HCT-116 and RKO respectively.

Conclusions

Collectively, these findings suggest that conjugating 5FU with other rapidly acting anti-tumor agents will efficiently accelerate the extermination of CRC cells. Therefore, combination therapy of baicalein with 5FU can be considered as a promising approach due to preventing proliferation, manipulating cell cycle, inducing apoptosis, and arresting the migration of CRC cells.