ABSTRACT
Acne is an inflammatory skin disorder in puberty with symptoms including papules, folliculitis, and nodules. Propionibacterium acnes (P. acnes) is the main anaerobic bacteria that cause acne. It is known to proliferate within sebum-blocked skin hair follicles. P. acnes activates monocytic cell immune responses to induce the expression of proinflammatory cytokines. Although the anti-inflammatory function of the Laurus nobilis (L. nobilis) extract (LNE) on several immunological disorders have been reported, the effect of LNE in P. acnes-mediated skin inflammation has not yet been explored. In the present study, we examined the ability of the LNE to modulate the P. acnes-induced inflammatory signaling pathway, and evaluated its mechanism. LNE significantly suppressed the expression of P. acnes-mediated proinflammatory cytokines, such as IL-1ß, IL-6, and NLRP3. We also found that LNE inhibited the inflammatory transcription factor NF-κB in response to P. acnes. In addition, eucalyptol, which is the main constituent of LNE, consistently inhibited P. acnes-induced inflammatory signaling pathways. Moreover, LNE significantly ameliorated P. acnes-induced inflammation in a mouse model of acne. We suggest for the first time that LNE hold therapeutic value for the improvement of P. acnes-induced skin inflammation.
Subject(s)
Acne Vulgaris/drug therapy , Anti-Inflammatory Agents/pharmacology , Eucalyptol/pharmacology , Gram-Positive Bacterial Infections/drug therapy , Laurus/chemistry , Plant Extracts/pharmacology , Propionibacterium acnes/growth & development , Acne Vulgaris/metabolism , Acne Vulgaris/microbiology , Acne Vulgaris/pathology , Animals , Anti-Inflammatory Agents/chemistry , Cell Line , Eucalyptol/chemistry , Gram-Positive Bacterial Infections/metabolism , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/pathology , Inflammation/drug therapy , Inflammation/metabolism , Inflammation/microbiology , Inflammation/pathology , Mice , Plant Extracts/chemistryABSTRACT
Ultraviolet B (UVB) radiation induces DNA damage, oxidative stress and inflammation, and suppresses the immune system in the skin, which collectively contribute to skin aging and carcinogenesis. The DNA damage response, including DNA repair, can be regulated by the circadian clock and microRNA (miRNA) expression. The aim of the present study was to evaluate the reparative action of Trichosanthes kirilowii extract (TKE) against UVB irradiationinduced DNA damage in human keratinocytes. TKE demonstrated low cytotoxicity in normal HaCaT keratinocytes at low doses (up to 100 µg/ml). The results of a comet assay revealed that TKE enhanced the repair of UVBinduced DNA damage. TKE significantly upregulated the expression of the core clock protein, brain and muscle aryl hydrocarbon receptor nuclear translocatorlike protein1 (BMAL1), and downregulated the expression of miRNA (miR)1423p, as demonstrated using western blotting and the reverse transcriptionquantitative polymerase chain reaction. Furthermore, the suppression of miR1423p by a specific inhibitor positively correlated with the repair activity. Overall, the data obtained demonstrated that TKE enhanced the repair of UVBinduced DNA damage by regulating the expression of BMAL1 and miR1423p. Consequently, TKE can be considered a potential candidate for the treatment of skin diseases associated with UVBinduced damage.
Subject(s)
ARNTL Transcription Factors/genetics , DNA Damage/radiation effects , DNA Repair/drug effects , Keratinocytes/drug effects , Keratinocytes/metabolism , MicroRNAs/genetics , Plant Extracts/pharmacology , Trichosanthes/chemistry , Ultraviolet Rays , Cell Line , Gene Expression Profiling , Gene Expression RegulationABSTRACT
In the present study, we investigated the roles and molecular mechanism of 10-gingerol, a phenolic compound isolated from Zingiber officinale, in regulating cell proliferation and invasion of MDAMB231 breast cancer cells. 10-gingerol treatment inhibited cell proliferation through downregulation of cell cycle regulatory proteins such as cyclin-dependent kinases and cyclins, and subsequent induction of G1 phase arrest. In addition, 10gingerol treatment blocked cell invasion in response to mitogenic stimulation. These antitumor activities of 10gingerol were mediated through inactivation of Akt and p38MAPK activity, and suppression of epidermal growth factor receptor expression. Collectively, these findings demonstrate the pharmacological roles of 10-gingerol in regulating breast cancer cell growth and progression, and suggest further evaluation and development as a potential therapeutic agent for the prevention and treatment of breast cancer.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Breast Neoplasms/pathology , Catechols/pharmacology , Cell Proliferation/drug effects , Fatty Alcohols/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism , Blotting, Western , Cell Line, Tumor , Female , Humans , Magnetic Resonance Spectroscopy , Neoplasm Invasiveness/pathology , Proto-Oncogene Proteins c-akt/drug effects , p38 Mitogen-Activated Protein Kinases/drug effectsABSTRACT
Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of allergic and inflammatory diseases. In the present study, we examined the effects and molecular mechanism of the ethanol extract of SG on cell proliferation and invasion in p53 wild-type A549 and p53-deficient H1299 non-small cell lung cancer (NSCLC) cells. SG treatment markedly inhibited the proliferation and invasion in both cell lines, independently of p53 expression. The anti-proliferative effect of SG on A549 cells was mediated by the inactivation of Akt and p70(S6K) as evidenced by treatment with LY294002 and rapamycin, respectively. In addition, anti-invasive activity of SG in A549 cells was found to be associated with the inhibition of p70(S6K). In contrast, in H1299 cells the inactivation of p38(MAPK) appeared to be involved in SG-mediated inhibition of cell proliferation and invasion. Collectively, these findings suggest that SG modulates cellular fates such as proliferation and invasion by differential regulation of signaling pathways, depending on the status of p53 expression in NSCLC, and support the development of SG as a potent therapeutic agent for the treatment of NSCLC.
Subject(s)
Antineoplastic Agents, Phytogenic , Asteraceae/chemistry , Carcinoma, Non-Small-Cell Lung/pathology , Cell Proliferation/drug effects , Cell Transformation, Neoplastic/drug effects , Lung Neoplasms/pathology , Plant Extracts/pharmacology , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Ethanol , Gene Expression/drug effects , Gene Silencing/drug effects , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Molecular Targeted Therapy , Neoplasm Invasiveness , Phytotherapy , Plant Extracts/therapeutic use , Proto-Oncogene Proteins c-akt/metabolism , Ribosomal Protein S6 Kinases, 70-kDa/metabolism , Tumor Suppressor Protein p53/metabolism , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
Integrin α3ß1 is expressed on many types of cancer cells and can regulate tumor growth and progression. In the present study, we examined the roles and molecular mechanism of integrin α3ß1 in modulating cell proliferation and migration of p53-deficient non-small cell lung cancer (NSCLC) cells. Reduced expression of integrin α3 by RNA silencing clearly induces cell proliferation and migration in H1299 cells, compared with those in control cells. Enhanced proliferation in integrin α3-silenced cells is mediated by upregulation and nuclear localization of cyclin-dependent kinases, and these effects require the activation of Akt and ERK as evidenced by treatment with LY294002 and PD98059, respectively. Furthermore, suppression of integrin α3 expression induces the expression of nuclear factor-κB and Bcl-2 as well as epidermal growth factor receptor, which are positively correlated with cell proliferation and survival. In contrast, increase in cell migration of integrin α3-silenced cells is found to be independent of Akt or ERK signaling pathways. Collectively, these findings suggest that integrin α3ß1 plays pivotal roles in regulating cell proliferation and migration that enhance the invasive type of p53-deficient NSCLC cells.