Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway
Abstract Background Lung cancer remains the most common cause of cancer-related deaths, with a high incidence and mortality in both sexes worldwide. Chemoprevention has been the most effective strategy for lung cancer prevention. Thus, exploring novel and effective candidate agents with low toxicity...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-06-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13046-019-1255-3 |
| _version_ | 1828309363266158592 |
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| author | Yanmei Lou Zhenzhen Guo Yuanfeng Zhu Muyan Kong Rongrong Zhang Linlin Lu Feichi Wu Zhongqiu Liu Jinjun Wu |
| author_facet | Yanmei Lou Zhenzhen Guo Yuanfeng Zhu Muyan Kong Rongrong Zhang Linlin Lu Feichi Wu Zhongqiu Liu Jinjun Wu |
| author_sort | Yanmei Lou |
| collection | DOAJ |
| description | Abstract Background Lung cancer remains the most common cause of cancer-related deaths, with a high incidence and mortality in both sexes worldwide. Chemoprevention has been the most effective strategy for lung cancer prevention. Thus, exploring novel and effective candidate agents with low toxicity for chemoprevention is essential and urgent. Houttuynia cordata Thunb. (Saururaceae) (H. cordata), which is a widely used herbal medicine and is also popularly consumed as a healthy vegetable, exhibits anti-inflammatory, antioxidant and antitumor activity. However, the chemopreventive effect of H. cordata against benzo(a)pyrene (B[a]P)-initiated lung tumorigenesis and the underlying mechanism remain unclear. Methods A B[a]P-stimulated lung adenocarcinoma animal model in A/J mice in vivo and a normal lung cell model (BEAS.2B) in vitro were established to investigate the chemopreventive effects of H. cordata and its bioactive compound 2-undecanone against lung tumorigenesis and to clarify the underlying mechanisms. Results H. cordata and 2-undecanone significantly suppressed B[a]P-induced lung tumorigenesis without causing obvious systemic toxicity in mice in vivo. Moreover, H. cordata and 2-undecanone effectively decreased B[a]P-induced intracellular reactive oxygen species (ROS) overproduction and further notably protected BEAS.2B cells from B[a]P-induced DNA damage and inflammation by significantly inhibiting phosphorylated H2A.X overexpression and interleukin-1β secretion. In addition, H. cordata and 2-undecanone markedly activated the Nrf2 pathway to induce the expression of the antioxidative enzymes heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Nrf2 silencing by transfection with Nrf2 siRNA markedly decreased the expression of HO-1 and NQO-1 to diminish the reductions in B[a]P-induced ROS overproduction, DNA damage and inflammation mediated by H. cordata and 2-undecanone. Conclusions H. cordata and 2-undecanone could effectively activate the Nrf2-HO-1/NQO-1 signaling pathway to counteract intracellular ROS generation, thereby attenuating DNA damage and inflammation induced by B[a]P stimulation and playing a role in the chemoprevention of B[a]P-induced lung tumorigenesis. These findings provide new insight into the pharmacological action of H. cordata and indicate that H. cordata is a novel candidate agent for the chemoprevention of lung cancer. |
| first_indexed | 2024-04-13T15:27:21Z |
| format | Article |
| id | doaj.art-0724fad6fdea49bfb2aba8ad29d5e013 |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-04-13T15:27:21Z |
| publishDate | 2019-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-0724fad6fdea49bfb2aba8ad29d5e0132022-12-22T02:41:28ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662019-06-0138112110.1186/s13046-019-1255-3Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathwayYanmei Lou0Zhenzhen Guo1Yuanfeng Zhu2Muyan Kong3Rongrong Zhang4Linlin Lu5Feichi Wu6Zhongqiu Liu7Jinjun Wu8Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineHunan Zhengqing Pharmaceutical Group LimitedJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineJoint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People’s Republic of China, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineAbstract Background Lung cancer remains the most common cause of cancer-related deaths, with a high incidence and mortality in both sexes worldwide. Chemoprevention has been the most effective strategy for lung cancer prevention. Thus, exploring novel and effective candidate agents with low toxicity for chemoprevention is essential and urgent. Houttuynia cordata Thunb. (Saururaceae) (H. cordata), which is a widely used herbal medicine and is also popularly consumed as a healthy vegetable, exhibits anti-inflammatory, antioxidant and antitumor activity. However, the chemopreventive effect of H. cordata against benzo(a)pyrene (B[a]P)-initiated lung tumorigenesis and the underlying mechanism remain unclear. Methods A B[a]P-stimulated lung adenocarcinoma animal model in A/J mice in vivo and a normal lung cell model (BEAS.2B) in vitro were established to investigate the chemopreventive effects of H. cordata and its bioactive compound 2-undecanone against lung tumorigenesis and to clarify the underlying mechanisms. Results H. cordata and 2-undecanone significantly suppressed B[a]P-induced lung tumorigenesis without causing obvious systemic toxicity in mice in vivo. Moreover, H. cordata and 2-undecanone effectively decreased B[a]P-induced intracellular reactive oxygen species (ROS) overproduction and further notably protected BEAS.2B cells from B[a]P-induced DNA damage and inflammation by significantly inhibiting phosphorylated H2A.X overexpression and interleukin-1β secretion. In addition, H. cordata and 2-undecanone markedly activated the Nrf2 pathway to induce the expression of the antioxidative enzymes heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO-1). Nrf2 silencing by transfection with Nrf2 siRNA markedly decreased the expression of HO-1 and NQO-1 to diminish the reductions in B[a]P-induced ROS overproduction, DNA damage and inflammation mediated by H. cordata and 2-undecanone. Conclusions H. cordata and 2-undecanone could effectively activate the Nrf2-HO-1/NQO-1 signaling pathway to counteract intracellular ROS generation, thereby attenuating DNA damage and inflammation induced by B[a]P stimulation and playing a role in the chemoprevention of B[a]P-induced lung tumorigenesis. These findings provide new insight into the pharmacological action of H. cordata and indicate that H. cordata is a novel candidate agent for the chemoprevention of lung cancer.http://link.springer.com/article/10.1186/s13046-019-1255-3Houttuynia cordata Thunb.2-undecanonebenzo(a)pyrenereactive oxygen speciesDNA damageinflammation |
| spellingShingle | Yanmei Lou Zhenzhen Guo Yuanfeng Zhu Muyan Kong Rongrong Zhang Linlin Lu Feichi Wu Zhongqiu Liu Jinjun Wu Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway Journal of Experimental & Clinical Cancer Research Houttuynia cordata Thunb. 2-undecanone benzo(a)pyrene reactive oxygen species DNA damage inflammation |
| title | Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway |
| title_full | Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway |
| title_fullStr | Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway |
| title_full_unstemmed | Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway |
| title_short | Houttuynia cordata Thunb. and its bioactive compound 2-undecanone significantly suppress benzo(a)pyrene-induced lung tumorigenesis by activating the Nrf2-HO-1/NQO-1 signaling pathway |
| title_sort | houttuynia cordata thunb and its bioactive compound 2 undecanone significantly suppress benzo a pyrene induced lung tumorigenesis by activating the nrf2 ho 1 nqo 1 signaling pathway |
| topic | Houttuynia cordata Thunb. 2-undecanone benzo(a)pyrene reactive oxygen species DNA damage inflammation |
| url | http://link.springer.com/article/10.1186/s13046-019-1255-3 |
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