The Effect of Phytochemicals on a Chemoresistant, Epithelial‐Mesenchymal Transitioned, Colorectal Cancer Cell Line
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In 2012, colorectal cancer was the second most common cancer diagnosed in women and the third most common in men. In 2015, an estimated 132,700 new individuals will be diagnosed and 49,700 people will die from the disease. Colorectal cancer, though one of the most common cancers worldwide, is not distributed evenly among the world's population. It is concentrated mainly in countries with a Western culture, specifically the Western diet, such as the United States and Western Europe. A considerably smaller rate of incidence of disease is found in Africa and parts of Asia. This difference in colorectal cancer distribution may be attributed to the increased presence of certain phytochemicals in non‐Western diets. Our hypothesis is that phytochemicals inhibit proliferation of both metastatic and non‐metastatic cancer cell lines. Studies have shown that transdifferentiation into epithelial‐mesenchymal transition (EMT) by chemotherapy leads to the formation of resistant cells. EMT is a process in which epithelial cells acquire a mesenchymal phenotype, characterized by increased migratory and invasive properties. We developed a chemoresistance‐induced epithelial to mesenchymal transitioned colon cancer cell line (DLD‐1 OxR) by exposing the parental cell line (DLD‐1) to increasing concentrations of oxaliplatin (a drug used in the treatment of metastatic colon cancer). The DLD‐1 OxR cell line has undergone EMT and lost its epithelial properties to become a more motile mesenchymal cell type. We used a wound healing assay and transwell assay to assess the migration and invasion of the EMT‐chemoresistant cell line respectively. DLD‐1 and DLD‐1 OxR cells were exposed to curcumin and kaempferol. Curcumin is a phytochemical derived from turmeric, which has been shown to suppress inflammation and inhibit cell proliferation. Kaempferol, a phytochemical found in plants such as broccoli, kale, beans, and leeks, has also shown anti‐inflammatory and anti‐cancerous activity. Both phytochemicals inhibited proliferation of DLD‐1 and DLD‐1 OxR cell lines. Support or Funding Information KM, KS, and AM are supported by the DeNardo Education and Research Foundation Fellowship.Keywords:
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Introduction Are dormant genes in differentiated cells activated? Does change in differentiated cell phenotypes occur in normal development? Examples of transdifferentiation among single or related cell classes Re-evaluation of classical examples of metaplasia and some related systems Does transdifferentiation occur in regeneration? Transdifferentiation in cell culture conditions Factors influencing transdifferentiation Characteristics of the transdifferentiation process References.
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Abstract Transdifferentiation (or metaplasia) refers to the conversion of one cell type to another. Because transdifferentiation normally occurs between cells that arise from the same region of the embryo, understanding the molecular and cellular events in cell type transformations may help to explain the mechanisms underlying normal development. Here we review examples of transdifferentiation in nature focusing on the possible role of cell type switching in metamorphosis and regeneration. We also examine transdifferentiation in mammals in relation to disease and the use of transdifferentiated cells in cellular therapy. Developmental Dynamics 236:3208–3217, 2007. © 2007 Wiley‐Liss, Inc.
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背景・目的: oxaliplatin base の化学療法が大腸癌腹膜播種症例に与える影響について検討した。対象・方法: 2006 年1月～2012 年11 月の間に，腹膜播種陽性Stage IV 大腸癌と診断され，oxaliplatin base の化学療法を導入した49 例（oxaliplatin施行群）と，それ以前に5─FU 系の全身化学療法を施行した26 例（control 群）を対象。oxaliplatin 導入前後のoverall survival（OS）を比較。また，oxaliplatin 施行群のOS に関して臨床病理学的因子を共変量とし，単変量，多変量解析を行い，予後因子を検討した。結果: oxalplatin 施行群はcontrol 群より有意に生存期間が延長していた（中央値 20.5 か月 vs 11.7 か月，p＝0.04）。oxaliplatin 施行群におけるOS に対するfavorable factor として，70 歳以下（p＝0.03），原発巣切除（p＝0.02）が同定された。結語: oxaliplatin base の化学療法は大腸癌腹膜播種症例においても生存期間を改善させた。腹膜播種の程度に関係なく原発巣切除を70 歳以下の症例に行い，速やかにoxaliplatin base の化学療法を導入することが予後向上につながることが示唆された。
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Colorectal cancer is one of the leading causes of cancer death. The mainstay of chemotherapy in colorectal cancer patients for the past 40 years has been fluorouracil (5-FU). Oxaliplatin (Eloxatin) is a novel platinum compound with promising activity in colorectal cancer. As a single agent, oxaliplatin has produced response rates of 12% to 24% in patients with previously untreated advanced colorectal cancer, and 10% to 11% in patients with relapsed or refractory advanced colorectal cancer. In phase II trials, oxaliplatin combined with 5-FU, with or without leucovorin, was associated with response rates of 60% and higher when used as front-line therapy, and when used in patients with relapsed or refractory advanced colorectal cancer, response rates ranged from 25% to 50%. In the front-line setting, two randomized trials of 5-FU and leucovorin, with or without oxaliplatin, demonstrated that the addition of oxaliplatin significantly increases response rate and time to tumor progression, but not survival, over 5-FU plus leucovorin alone. The reasons for this discrepancy are unclear, and several possibilities are being considered. Additional phase III trials are underway to clarify the contribution of oxaliplatin in the treatment of patients with locally advanced and metastatic colorectal cancer.
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