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Potentiating effect of cepharanthine in combination with 5-fluorouracil on human colorectal cancer cells |
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| รหัสดีโอไอ | |
| Title | Potentiating effect of cepharanthine in combination with 5-fluorouracil on human colorectal cancer cells |
| Creator | Sukanya Unson |
| Contributor | Piyanuch Wonganan, Chandhanee Itthipanichpong |
| Publisher | Chulalongkorn University |
| Publication Year | 2558 |
| Keyword | Rectum -- Cancer, Antineoplastic agents, Fluorouracil, เรคตัม -- มะเร็ง, ยารักษามะเร็ง, ฟลูออโรยูเรซิล |
| Abstract | 5-Fluorouracil (5-FU) is widely used as a first line drug for patients with colorectal cancer. The use of this drug has however been limited by drug resistance and serious side effects. Several preclinical studies reported that cepharanthine (CEP), a biscoclaurine alkaloid, possesses not only anticancer activity but also chemopotentiation effect. This study intended to determine the potentiating effect of CEP on anticancer effect of 5-FU in colorectal cancer cells. The results clearly demonstrated that CEP significantly enhanced cytotoxic activity of 5-FU in HT-29 cells. Although treatment with 5-FU alone could trigger cancer cells to undergo apoptosis, an increase in necrotic cell death was detected following treatment with 5-FU in combination with CEP. Real-time PCR analysis indicated that down-regulation of Bcl-2 gene expression caused by 5-FU alone was further decreased following treatment with 5-FU and CEP. In addition, the combination treatment could significantly inhibit cell cycle progression in S phase. CEP however did not alter mRNA levels and activities of P-gp, MRP1, or BCRP drug efflux transporters in HT-29 cells. Taken together, the results from this study suggest that the chemopotentiation of 5-FU by CEP may be associated with induction of necrosis, down-regulation of Bcl-2, as well as alteration of cell cycle progression and CEP may potentially be used as an adjuvant agent for enhancing 5-FU potency in colorectal cancer treatment. |
| URL Website | cuir.car.chula.ac.th |