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

Autor: Zhongqiu Liu, Muyan Kong, Lu Linlin, Rong-Rong Zhang, Jinjun Wu, Zhenzhen Guo, Yuanfeng Zhu, Yanmei Lou, Feichi Wu
Rok vydání: 2019
Předmět:
0301 basic medicine
Male
Cancer Research
Intracellular Space
medicine.disease_cause
chemistry.chemical_compound
Mice
0302 clinical medicine
NAD(P)H Dehydrogenase (Quinone)
chemistry.chemical_classification
reactive oxygen species
biology
Cell Cycle
Ketones
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Houttuynia cordata
Cell Transformation
Neoplastic
Oncology
Benzo(a)pyrene
030220 oncology & carcinogenesis
nuclear factor E2-related factor-2
medicine.symptom
Signal Transduction
2-undecanone
DNA damage
NF-E2-Related Factor 2
Inflammation
lcsh:RC254-282
Houttuynia cordata Thunb
03 medical and health sciences
Cell Line
Tumor
medicine
Animals
Humans
Houttuynia
Lung cancer
Cell Proliferation
Reactive oxygen species
Plant Extracts
Research
medicine.disease
biology.organism_classification
Antineoplastic Agents
Phytogenic
Disease Models
Animal
030104 developmental biology
chemistry
Apoptosis
inflammation
Cancer research
benzo(a)pyrene
Carcinogenesis
Heme Oxygenase-1
Zdroj: Journal of Experimental & Clinical Cancer Research : CR
Journal of Experimental & Clinical Cancer Research
Journal of Experimental & Clinical Cancer Research, Vol 38, Iss 1, Pp 1-21 (2019)
ISSN: 1756-9966
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s13046-019-1255-3) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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