Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis
Hepatocellular carcinoma (HCC) is difficult to treat, and is the second leading cause of cancer-related death worldwide. This study aimed to examine whether combination of wogonin and artesunate exhibits synergistic anti-HCC effect. Our data show that the combination treatment exhibits synergistic e...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.657080/full |
| _version_ | 1818940110384660480 |
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| author | Minting Chen Hsin Ling Wu Tsz Sin Wong Baisen Chen Rui-Hong Gong Hoi Leong Xavier Wong Haitao Xiao Zhaoxiang Bian Hiu Yee Kwan |
| author_facet | Minting Chen Hsin Ling Wu Tsz Sin Wong Baisen Chen Rui-Hong Gong Hoi Leong Xavier Wong Haitao Xiao Zhaoxiang Bian Hiu Yee Kwan |
| author_sort | Minting Chen |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC) is difficult to treat, and is the second leading cause of cancer-related death worldwide. This study aimed to examine whether combination of wogonin and artesunate exhibits synergistic anti-HCC effect. Our data show that the combination treatment exhibits synergistic effect in reducing HCC cell viability by increasing apoptosis as indicated by the elevated cleavage of caspase 8, 3 and PARP. Interestingly, PCR array and the subsequent studies indicate that the combination treatment significantly increases the expression of DNA-damage-inducible, alpha (GADD45A), tumor necrosis factor (TNFα) and TNF receptor-associated factor 3 (TRAF3). Knockdown of GADD45A, TNFα or TRAF3 abolishes the combination treatment-enhanced apoptosis and the synergistic effect in reducing HCC cell viability. In the HCC-bearing xenograft mouse models, although the combination treatment increases the activity of NFκB in the tumor tissues, it exhibits a more potent anti-HCC effect than the mono-treatment, which may due to the enhanced apoptosis as indicated by the increased expression of GADD45A, TNFα, TRAF3 and apoptotic markers. Our study clearly demonstrates that the combination of artesunate and wogonin exhibits synergistic anti-HCC effect, and support the further development of this combination as alternative therapeutics for HCC management. |
| first_indexed | 2024-12-20T06:34:26Z |
| format | Article |
| id | doaj.art-6cabde6553754f15b95d01c2f272915f |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-20T06:34:26Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-6cabde6553754f15b95d01c2f272915f2022-12-21T19:50:02ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.657080657080Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated ApoptosisMinting Chen0Hsin Ling Wu1Tsz Sin Wong2Baisen Chen3Rui-Hong Gong4Hoi Leong Xavier Wong5Haitao Xiao6Zhaoxiang Bian7Hiu Yee Kwan8Centre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaCentre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaCentre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaCentre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaCentre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaCentre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaSchool of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen, ChinaCentre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaCentre for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, ChinaHepatocellular carcinoma (HCC) is difficult to treat, and is the second leading cause of cancer-related death worldwide. This study aimed to examine whether combination of wogonin and artesunate exhibits synergistic anti-HCC effect. Our data show that the combination treatment exhibits synergistic effect in reducing HCC cell viability by increasing apoptosis as indicated by the elevated cleavage of caspase 8, 3 and PARP. Interestingly, PCR array and the subsequent studies indicate that the combination treatment significantly increases the expression of DNA-damage-inducible, alpha (GADD45A), tumor necrosis factor (TNFα) and TNF receptor-associated factor 3 (TRAF3). Knockdown of GADD45A, TNFα or TRAF3 abolishes the combination treatment-enhanced apoptosis and the synergistic effect in reducing HCC cell viability. In the HCC-bearing xenograft mouse models, although the combination treatment increases the activity of NFκB in the tumor tissues, it exhibits a more potent anti-HCC effect than the mono-treatment, which may due to the enhanced apoptosis as indicated by the increased expression of GADD45A, TNFα, TRAF3 and apoptotic markers. Our study clearly demonstrates that the combination of artesunate and wogonin exhibits synergistic anti-HCC effect, and support the further development of this combination as alternative therapeutics for HCC management.https://www.frontiersin.org/articles/10.3389/fphar.2021.657080/fullartesunatewogoninhepatocellular carcinomaGADD45aGADD45tumor necrosis factor-α |
| spellingShingle | Minting Chen Hsin Ling Wu Tsz Sin Wong Baisen Chen Rui-Hong Gong Hoi Leong Xavier Wong Haitao Xiao Zhaoxiang Bian Hiu Yee Kwan Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis Frontiers in Pharmacology artesunate wogonin hepatocellular carcinoma GADD45a GADD45 tumor necrosis factor-α |
| title | Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis |
| title_full | Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis |
| title_fullStr | Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis |
| title_full_unstemmed | Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis |
| title_short | Combination of Wogonin and Artesunate Exhibits Synergistic anti-Hepatocellular Carcinoma Effect by Increasing DNA-Damage-Inducible Alpha, Tumor Necrosis Factor α and Tumor Necrosis Factor Receptor-Associated Factor 3-mediated Apoptosis |
| title_sort | combination of wogonin and artesunate exhibits synergistic anti hepatocellular carcinoma effect by increasing dna damage inducible alpha tumor necrosis factor α and tumor necrosis factor receptor associated factor 3 mediated apoptosis |
| topic | artesunate wogonin hepatocellular carcinoma GADD45a GADD45 tumor necrosis factor-α |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.657080/full |
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