Enhancement of TRAIL-induced apoptosis by 5-fluorouracil requires activating Bax and p53 pathways in TRAIL-resistant lung cancers.
Lung cancer, especially lung adenocarcinoma, is one of the main causes of death worldwide. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a primary anticancer agent and a member of the tumor necrosis factor family that selectively induces apoptosis in various tumor cells, but not in normal cells. Combination chemotherapy can be used for treating specific cancer types even at progressive stages. In the present study, we observed that 5-fluorouracil, which exerts anticancer effects by inhibiting tumor cell proliferation, enhanced TRAIL-induced apoptosis of TRAIL-resistant human adenocarcinoma A549 cells. Interestingly, 5-fluorouracil treatment markedly increased Bax and p53 levels and 5-fluorouracil and TRAIL cotreatment increased Ac-cas3 and Ac-cas8 levels compared with those in control cells. Taken together, the present study demonstrated that 5-fluorouracil enhances TRAIL-induced apoptosis in TRAIL-resistant lung adenocarcinoma cells by activating Bax and p53, and also suggest that TRAIL and 5-fluorouracil cotreatment can be used as an adequate therapeutic strategy for TRAIL-resistant human cancers.
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea.
Uddin Md
UM
Nazim
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea.
Mohammad
M
Rasheduzzaman
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea.
You-Jin
YJ
Lee
Faculty of Pharmacy, Chung-Ang University School of Pharmacy, Seoul 156-756, Republic of Korea.
Dai-Wu
DW
Seol
Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Iksan, Jeonbuk 54596, Republic of Korea.
Sang-Youel
SY
Park
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494826:BAX protein, human; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D005472:Fluorouracil
5-fluorouracil; TRAIL; apoptosis; lung cancer cells