Tetramethylpyrazine Enhances the Antitumor Effect of Paclitaxel by Inhibiting Angiogenesis and Inducing Apoptosis
Recent published findings have demonstrated the effectiveness of combining molecules from traditional Chinese medicine with chemotherapeutic drugs to treat cancer. Combined administration of these agents can overcome drug-mitigating responses as well as reduce adverse side effects, thereby enhancing...
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Frontiers Media S.A.
2019-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.00707/full |
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| author | Liang Zou Liang Zou Xiaowei Liu Jingjing Li Wei Li Lele Zhang Jian Li Jinming Zhang |
| author_facet | Liang Zou Liang Zou Xiaowei Liu Jingjing Li Wei Li Lele Zhang Jian Li Jinming Zhang |
| author_sort | Liang Zou |
| collection | DOAJ |
| description | Recent published findings have demonstrated the effectiveness of combining molecules from traditional Chinese medicine with chemotherapeutic drugs to treat cancer. Combined administration of these agents can overcome drug-mitigating responses as well as reduce adverse side effects, thereby enhancing the efficacy of the therapy. Tetramethylpyrazine (TMP), an alkaloid monomer from the medicinal herb Ligusticum chuanxiong hort, is known to exert a variety of antitumor effects including inhibition of tumor cell proliferation, metastasis, and drug resistance. In this research, we investigated antitumor effects of TMP combined with paclitaxel (PTX), a frontline chemotherapeutic drug, in vitro and in vivo. Our results indicate that TMP enhances the antitumor effects of PTX in ovarian cancer A2780 and SKOV3 cells. Furthermore, we found that combined treatment of TMP and PTX suppressed angiogenesis by inhibiting both ERK1/2 and Akt pathways and promoted apoptosis of tumor cells compared to TMP or PTX treatment alone. Moreover, TMP augmented the antitumor effects of PTX in ovarian cancer A2780 xenograft mouse models by significantly decreasing tumor burden and partially decreasing the toxicity of PTX, as evidenced by the decreased expression of proliferation and angiogenesis markers as well as the hematoxylin and eosin (H&E) staining and biochemical indexes assay. Overall, our findings provide novel mechanistic insight into the efficacy of combining of potent molecules present in traditional Chinese medicine with chemotherapeutic drugs for therapeutic intervention in cancer. |
| first_indexed | 2024-04-13T17:35:10Z |
| format | Article |
| id | doaj.art-75fef99219cf4434b5f225f735051b84 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-13T17:35:10Z |
| publishDate | 2019-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-75fef99219cf4434b5f225f735051b842022-12-22T02:37:24ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-06-011010.3389/fphar.2019.00707445053Tetramethylpyrazine Enhances the Antitumor Effect of Paclitaxel by Inhibiting Angiogenesis and Inducing ApoptosisLiang Zou0Liang Zou1Xiaowei Liu2Jingjing Li3Wei Li4Lele Zhang5Jian Li6Jinming Zhang7School of Medicine, Chengdu University, Chengdu, ChinaKey Laboratory of Coarse Cereal Processing, Ministry of Agriculture and Rural Affairs, Chengdu University, Chengdu, ChinaSchool of Medicine, Chengdu University, Chengdu, ChinaDepartment of Pharmacy and Pharmacology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong KongSchool of Medicine, Chengdu University, Chengdu, ChinaSchool of Medicine, Chengdu University, Chengdu, ChinaSchool of Medicine, Chengdu University, Chengdu, ChinaSchool of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, ChinaRecent published findings have demonstrated the effectiveness of combining molecules from traditional Chinese medicine with chemotherapeutic drugs to treat cancer. Combined administration of these agents can overcome drug-mitigating responses as well as reduce adverse side effects, thereby enhancing the efficacy of the therapy. Tetramethylpyrazine (TMP), an alkaloid monomer from the medicinal herb Ligusticum chuanxiong hort, is known to exert a variety of antitumor effects including inhibition of tumor cell proliferation, metastasis, and drug resistance. In this research, we investigated antitumor effects of TMP combined with paclitaxel (PTX), a frontline chemotherapeutic drug, in vitro and in vivo. Our results indicate that TMP enhances the antitumor effects of PTX in ovarian cancer A2780 and SKOV3 cells. Furthermore, we found that combined treatment of TMP and PTX suppressed angiogenesis by inhibiting both ERK1/2 and Akt pathways and promoted apoptosis of tumor cells compared to TMP or PTX treatment alone. Moreover, TMP augmented the antitumor effects of PTX in ovarian cancer A2780 xenograft mouse models by significantly decreasing tumor burden and partially decreasing the toxicity of PTX, as evidenced by the decreased expression of proliferation and angiogenesis markers as well as the hematoxylin and eosin (H&E) staining and biochemical indexes assay. Overall, our findings provide novel mechanistic insight into the efficacy of combining of potent molecules present in traditional Chinese medicine with chemotherapeutic drugs for therapeutic intervention in cancer.https://www.frontiersin.org/article/10.3389/fphar.2019.00707/fulltetramethylpyrazinepaclitaxelangiogenesisapoptosisantitumor effect |
| spellingShingle | Liang Zou Liang Zou Xiaowei Liu Jingjing Li Wei Li Lele Zhang Jian Li Jinming Zhang Tetramethylpyrazine Enhances the Antitumor Effect of Paclitaxel by Inhibiting Angiogenesis and Inducing Apoptosis Frontiers in Pharmacology tetramethylpyrazine paclitaxel angiogenesis apoptosis antitumor effect |
| title | Tetramethylpyrazine Enhances the Antitumor Effect of Paclitaxel by Inhibiting Angiogenesis and Inducing Apoptosis |
| title_full | Tetramethylpyrazine Enhances the Antitumor Effect of Paclitaxel by Inhibiting Angiogenesis and Inducing Apoptosis |
| title_fullStr | Tetramethylpyrazine Enhances the Antitumor Effect of Paclitaxel by Inhibiting Angiogenesis and Inducing Apoptosis |
| title_full_unstemmed | Tetramethylpyrazine Enhances the Antitumor Effect of Paclitaxel by Inhibiting Angiogenesis and Inducing Apoptosis |
| title_short | Tetramethylpyrazine Enhances the Antitumor Effect of Paclitaxel by Inhibiting Angiogenesis and Inducing Apoptosis |
| title_sort | tetramethylpyrazine enhances the antitumor effect of paclitaxel by inhibiting angiogenesis and inducing apoptosis |
| topic | tetramethylpyrazine paclitaxel angiogenesis apoptosis antitumor effect |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.00707/full |
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