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Published on: May 9, 2020
Triptolide inhibits cyclooxygenase-2 and inducible nitric oxide synthase expression in human colon cancer and
Xiangmin Tong1, Shui'er Zheng, Jie Jin
1Institute of Hematologic Disease, Department of Hematology, First Affiliated Hospital, Medical School, Zhejiang University, Hangzhou 310003, China. yaohp2001@yahoo.com.cn.
Abstract:
Triptolide (TP), a traditional Chinese medicine, has been reported to be effective in the treatment of autoimmune diseases and exerting antineoplastic activity in several human tumor cell lines. This study investigates the antitumor effect of TP in human colon cancer cells (SW114) and myelocytic leukemia (K562), and elucidates the possible molecular mechanism involved. SW114 and K562 cells were treated with different doses of TP (0, 5, 10, 20, or 50 ng/ml). The cell viability was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT). Results demonstrated that TP inhibited the proliferation of both tumor cell lines in a dose-dependent manner. To further investigate its mechanisms, the products prostaglandin E(2) (PGE(2)) and nitric oxide (NO) were measured by enzyme-linked immunosorbent assay (ELISA). Our data showed that TP strongly inhibited the production of NO and PGE(2). Consistent with these results, the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) was up-regulated both at the mRNA level and the protein expression level, as shown by real-time RT-PCR and Western blotting. These results indicated that the inhibition of the inflammatory factor COX-2 and iNOS activity could be involved in the antitumor mechanisms of TP.
Insights
Triptolide (TP) demonstrates significant antitumor effects by inhibiting the proliferation of colon cancer and leukemia cells. Its mechanism involves down-regulating inflammatory factors like nitric oxide (NO) and prostaglandin E2 (PGE2).
Area of Science:
- Pharmacology and Toxicology
- Cancer Biology
- Immunology
Background:
- Triptolide (TP), a compound from traditional Chinese medicine, shows promise for autoimmune diseases and possesses antineoplastic activity.
- Existing research indicates TP's potential against various human tumor cell lines.
- The precise molecular mechanisms underlying TP's antitumor effects require further elucidation.
Purpose of the Study:
- To investigate the antitumor efficacy of Triptolide (TP) in human colon cancer (SW114) and myelocytic leukemia (K562) cell lines.
- To explore the molecular mechanisms associated with TP's anti-cancer activity, focusing on inflammatory pathways.
Main Methods:
- Human colon cancer (SW114) and myelocytic leukemia (K562) cells were treated with varying concentrations of TP (0-50 ng/ml).
- Cell viability was assessed using the MTT assay.
- Production of nitric oxide (NO) and prostaglandin E2 (PGE2) was quantified via ELISA; mRNA and protein expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) were analyzed using real-time RT-PCR and Western blotting.
Main Results:
- TP significantly inhibited the proliferation of both SW114 and K562 cells in a dose-dependent manner.
- TP markedly suppressed the production of NO and PGE2.
- TP treatment led to the down-regulation of iNOS and COX-2 at both mRNA and protein levels.
Conclusions:
- Triptolide exhibits potent antitumor effects against human colon cancer and leukemia cells.
- The anti-cancer mechanism of TP is associated with the inhibition of key inflammatory mediators, specifically iNOS and COX-2.
- TP's ability to modulate inflammatory pathways suggests its potential as a therapeutic agent for cancer treatment.
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