8 research outputs found

    The Combination of Three Natural Compounds Effectively Prevented Lung Carcinogenesis by Optimal Wound Healing

    No full text
    <div><p>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.</p></div

    The wound healing microenvironment restored GJIC but did not directly decrease tumor cells.

    No full text
    <p><b>(</b>A) The combination of three compounds reversed GJIC loss in urethane-treated BEAS-2B cells. Images were taken at ×10 magnification. (B and C) The combination of three compounds led to angiogenesis and optimal fibroblast proliferation but did not directly decrease A549 cancer cells. The results are presented as mean±SE (n = 5/group) **<i>p</i> < 0.01 <i>vs</i> control group.</p

    The screened three wound healing agents suppressed lung carcinogenesis and their combination led to optimal preventive efficacy.

    No full text
    <p>(A) Three wound healing agents were administered to animals following the first carcinogen treatment and were found to prevent lung carcinogenesis. (B) They were administered following the last carcinogen treatment but did not prevent lung carcinogenesis, whereas the combination of these three agents remained effective. (C) Summary data of lung tumor incidence (n = 20). (D) Three wound healing agents restored the lung barrier in urethane-induced lung carcinogenesis. The results are presented as mean±SE (n = 10/group). *<i>p</i> < 0.05, **<i>p</i> < 0.01, vs control group.</p

    The wound healing microenvironment prevented lung cell malignant transformation.

    No full text
    <p>(A) The combination of three compounds reduced the population expressing stem cell markers or EMT markers examined by flow cytometry and in A549 cells. (B) The combination of three compounds decreased A549 cell self-renew shown as the number of tumor spheres and soft agar colonies. (C) The combination of three compounds decreased the population expressing EMT markers examined by flow cytometry in urethane-treated BEAS-2B cells. The results are presented as mean±SE (n = 5/group) **<i>p</i> < 0.01 <i>vs</i> control group.</p

    The combined models increased lung tumor overall volume but did not negatively impact health or significantly affect the body weights of mice.

    No full text
    <p>(A) The combined models increased lung tumor overall volume and decreased carcinogenic preventive efficacy of a single compound. (B-E) The combined models did not negatively impact health or significantly affect the body weights of mice. The results are presented as mean±SE (n = 20/group). **<i>p</i> < 0.01, vs control group.</p

    Urethane-induced lung carcinogenesis was associated with lung injury independent of pulmonary inflammation.

    No full text
    <p>(A) Urethane-induced lung carcinogenesis was promoted by BLM- or macrophage depletion-induced lung injury but was not affected by LPS-induced pulmonary inflammation. (B-D) LPS exposure, BLM exposure and macrophage depletion reversed carcinogenic preventive efficacy of single compound but had slight effect on combined efficacy shown as lung tumor incidence, lung tumor number and lung weight, respectively. The results are presented as mean±SE (n = 20/group). *<i>p</i> < 0.05, **<i>p</i> < 0.01, vs control group.</p

    The screened three wound healing agents desereased lung tumor overall volume and did not negatively impact health or significantly affect the body weights of mice.

    No full text
    <p>(A) Three wound healing agents desereased lung tumor overall volume. (B-D) Three wound healing agents did not negatively impact health or significantly affect the body weights of mice. The results are presented as mean±SE (n = 10/group). *<i>p</i> < 0.05, **<i>p</i> < 0.01, vs control group.</p

    The pharmacological properties of screened three wound healing agents.

    No full text
    <p>(A) Screened three compounds promoted wound closure in a skin excision wound model. (B) Notoginsenoside R1 and aconitine increased blood flow perfusion on laser speckle imaging. (C) Shikonin exerted anti-inflammatory efficacy in the TPA-induced ear edema model. (D) Notoginsenoside R1 and aconitine promoted macrophage phagocytosis of zymosan. The results are presented as mean±SE (n = 10/group). ** <i>p</i> < 0.01, vs. control group.</p
    corecore