Article

Digestive Diseases and Sciences

, Volume 50, Issue 6, pp 1025-1032

First online:

Apoptosis Induced by Aspirin and 5-Fluorouracil in Human Colonic Adenocarcinoma Cells

  • Hassan AshktorabAffiliated withDepartment of Medicine, Divisions of Hematology/Oncology and Gastroenterology and Howard University Cancer Center, Howard UniversityCancer Center and Department of Medicine, Howard University Email author 
  • , Fitzroy W. DawkinsAffiliated withDepartment of Medicine, Divisions of Hematology/Oncology and Gastroenterology and Howard University Cancer Center, Howard University
  • , Rihab MohamedAffiliated withDepartment of Medicine, Divisions of Hematology/Oncology and Gastroenterology and Howard University Cancer Center, Howard University
  • , Daniel LarbiAffiliated withDepartment of Medicine, Divisions of Hematology/Oncology and Gastroenterology and Howard University Cancer Center, Howard University
  • , Duane T. SmootAffiliated withDepartment of Medicine, Divisions of Hematology/Oncology and Gastroenterology and Howard University Cancer Center, Howard University

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Abstract

Various biochemical, clinical and epidemiological studies have shown that aspirin (ASA) and other nonsteroidal anti-inflammatory drugs (NSAIDs) demonstrate antineoplastic properties, particularly in the gastrointestinal tract, inhibiting the proliferation of colorectal cancer cells. The mechanism of action may be prostaglandin mediated through inhibition of the COX enzymatic system. This includes two iso-enzymes, COX-I and COX-II, working in concert with the activation of apoptosis, activation of immune surveillance, inhibition of proliferation, and inhibition of carcinogen activation. 5-Fluorouracil (5-FU) has demonstrated activity against colorectal cancer, leading to apoptosis of neoplastic cells. We evaluated the effects of varying doses of ASA (0.5, 1, 1.5 mM), both as a single agent and in combination with 5-FU (50 μg) in HT-29, a colon adenocarcinoma cell line. Proliferation assays showed that aspirin at a concentration of 1 mM inhibits cell growth. Cells treated with ASA, both alone and in combination with 5-FU, demonstrated apoptotic activity with the up-regulation of Bax protein, which is consistent with 5-FU anticancer treatment. Furthermore, there was synergistic cell death with ASA and 5-FU. DNA fragmentation, TUNEL, and trypan blue exclusion methods indicated that a combination of ASA and 5-FU induces apoptosis in cells in a time- and concentration-dependent manner. This study serves to further elucidate the mechanism of action of ASA, and ASA in combination with 5-FU, in colorectal cancer as evidenced by its effect on the HT-29 cell line.

Key Words

apoptosis aspirin 5-fluorouacil human colonic adenocarcinoma cells HT-29 cells