Effects of ellagic acid on chemosensitivity to 5-fluorouracil in colorectal carcinoma cells.
Ellagic acid has been demonstrated to inhibit the growth of several types of cancer cells. However, whether it sensitizes human colorectal carcinoma cells to 5-fluorouracil, has not yet been investigated. Colorectal carcinoma HT-29, Colo 320DM, SW480 and LoVo cells were treated with ellagic acid (2.5-25 μg/ml) and 5-fluorouracil (5-25 μM) alone and in combination and then the viability was assessed by trypan blue exclusion, apoptosis by annexin-V labeling, mitochondria membrane potential by staining with rhodamine 123, and changes in the levels of proteins involved in apoptosis by immunoblotting. Ellagic acid and 5-fluorouracil synergistically inhibited cell proliferation of HT-29, Colo 320DM and SW480 cells, but cytotoxicity toward LoVo cells seems not to be potentiated by this combination. The combination also elevated apoptotic cell death of HT-29 and Colo 320DM cells. The mitochondria membrane potential was lost in combination-treated HT-29 cells, due to increased B cell lymphoma 2-associated protein X (BAX): B cell lymphoma 2 protein (BCL-2) ratio and caspase-3 activity. Ellagic acid synergistically potentiated chemosensitivity to 5-fluorouracil in at least three colorectal cancer cell lines. The results indicate that ellagic acid has potential as a novel agent sensitizing colorectal cancer cells to 5-fluorouracil.
Department of Medical Laboratory Science and Biotechnology, Yuanpei University, Hsinchu City, Taiwan, ROC.
Ting-Yu
TY
Kao
Yuan-Chiang
YC
Chung
Yung-Chi
YC
Hou
Yin-Wen
YW
Tsai
Chin-Hui
CH
Chen
Hsin-Ping
HP
Chang
Jui-Ling
JL
Chou
Chih-Ping
CP
Hsu
D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004357:Drug Synergism; D004610:Ellagic Acid / Q000494:pharmacology*; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
D000970:Antineoplastic Agents; C494826:BAX protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D004610:Ellagic Acid; C505407:CASP3 protein, human; D053148:Caspase 3; D005472:Fluorouracil