The Combination of Three Natural Compounds Effectively Prevented Lung Carcinogenesis by Optimal Wound Healing
Autor: | Shengnan Geng, Gangjun Du, Linxin Liu, Yaqiu Zheng, Yongjian Duan, Zhenzhen Guo, Ning Cao, Hong Li, Xiaofang Ma, Guang Han |
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Jazyk: | angličtina |
Rok vydání: | 2015 |
Předmět: |
Pathology
medicine.medical_specialty Lung Neoplasms Carcinogenesis lcsh:Medicine Inflammation Apoptosis Lung injury medicine.disease_cause Models Biological Urethane Cell Line medicine Adenocarcinoma of the lung Tumor Microenvironment Animals Humans Lung cancer lcsh:Science Tumor microenvironment Biological Products Mice Inbred BALB C Wound Healing Multidisciplinary integumentary system business.industry Body Weight lcsh:R Cancer Cell Differentiation Lung Injury Pneumonia medicine.disease Cell Transformation Neoplastic Cancer research Neoplastic Stem Cells Female lcsh:Q medicine.symptom business Wound healing Research Article |
Zdroj: | PLoS ONE, Vol 10, Iss 11, p e0143438 (2015) PLoS ONE |
ISSN: | 1932-6203 |
Popis: | The tumor stroma has been described as "normal wound healing gone awry". We explored whether the restoration of a wound healing-like microenvironment may facilitate tumor healing. Firstly, we screened three natural compounds (shikonin, notoginsenoside R1 and aconitine) from wound healing agents and evaluated the efficacies of wound healing microenvironment for limiting single agent-elicited carcinogenesis and two-stage carcinogenesis. The results showed that three compounds used alone could promote wound healing but had unfavorable efficacy to exert wound healing, and that the combination of three compounds made up treatment disadvantage of a single compound in wound healing and led to optimal wound healing. Although individual treatment with these agents may prevent cancer, they were not effective for the treatment of established tumors. However, combination treatment with these three compounds almost completely prevented urethane-induced lung carcinogenesis and reduced tumor burden. Different from previous studies, we found that urethane-induced lung carcinogenesis was associated with lung injury independent of pulmonary inflammation. LPS-induced pulmonary inflammation did not increase lung carcinogenesis, whereas decreased pulmonary inflammation by macrophage depletion promoted lung carcinogenesis. In addition, urethane damaged wound healing in skin excision wound model, reversed lung carcinogenic efficacy by the combination of three compounds was consistent with skin wound healing. Further, the combination of these three agents reduced the number of lung cancer stem cells (CSCs) by inducing cell differentiation, restoration of gap junction intercellular communication (GJIC) and blockade of the epithelial-to-mesenchymal transition (EMT). Our results suggest that restoration of a wound healing microenvironment represents an effective strategy for cancer prevention. |
Databáze: | OpenAIRE |
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