p-Cymene Modulates In Vitro and In Vivo Cytokine Production by Inhibiting MAPK and NF-κB Activation

Zhong, Weiying; Chi, Gefu; Jiang, Lanxiang; Soromou, Lanan Wassy; Chen, Na; Huo, Meixia; Guo, Wei; Deng, Xuming; Feng, Hailan

doi:10.1007/s10753-012-9574-y

Cited by 47 publications

(38 citation statements)

References 35 publications

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“…In C57BL/6 mice, TNF-α and IL-1β were downregulated and IL-10 was upregulated by p-cymene treatment. It also inhibited LPS-induced activation of ERK 1/2, p38, JNK, and IκBα (32,33). …”

Section: Terpenes With Anti-inflammatory Functionmentioning

confidence: 96%

Terpenes from Forests and Human Health

et al. 2017

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Forest bathing has beneficial effects on human health via showering of forest aerosols as well as physical relaxation. Terpenes that consist of multiple isoprene units are the largest class of organic compounds produced by various plants, and one of the major components of forest aerosols. Traditionally, terpene-containing plant oil has been used to treat various diseases without knowing the exact functions or the mechanisms of action of the individual bioactive compounds. This review categorizes various terpenes easily obtained from forests according to their anti-inflammatory, anti-tumorigenic, or neuroprotective activities. Moreover, potential action mechanisms of the individual terpenes and their effects on such processes, which are described in various in vivo and in vitro systems, are discussed. In conclusion, the studies that show the biological effectiveness of terpenes support the benefits of forest bathing and propose a potential use of terpenes as chemotherapeutic agents for treating various human diseases.

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“…In C57BL/6 mice, TNF-α and IL-1β were downregulated and IL-10 was upregulated by p-cymene treatment. It also inhibited LPS-induced activation of ERK 1/2, p38, JNK, and IκBα (32,33). …”

Section: Terpenes With Anti-inflammatory Functionmentioning

confidence: 96%

Terpenes from Forests and Human Health

et al. 2017

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“…After follicle colonisation, P. acnes induces a suite of inflammatory changes such as the production of cytokines by host tissues and activation of the innate immune response via Toll-like receptor 2 [39,41]. A number of studies have shown in vitro that tea tree oil or major components suppress inflammation [42]. Cytokine production by human monocytes (but not neutrophils) [43,44] and macrophages [45] is inhibited by tea tree oil and the major component terpinen-4-ol [46].…”

Section: Properties Of Tea Tree Oil Contributing To Clinical Efficacymentioning

confidence: 99%

Treatment of acne with tea tree oil (melaleuca) products: A review of efficacy, tolerability and potential modes of action

Hammer

2015

International Journal of Antimicrobial Agents

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“…17,30,31) We demonstrated that p-cymene suppressed the phosphorylation of ERK1/2 and p38 MAPK in TPA-treated HT-1080 cells, suggesting that the concomitant suppression of the ERK1/2 and p38 MAPK signal pathways by p-cymene at least partially results in the down-regulation of MMP-9 production. Moreover, as monoterpenoids including p-cymene have been reported to potentially inhibit the NF-κB signal pathway, 7,32) the inhibition of NF-κB may be associated with the p-cymene-decreased expression of MMP-9 in TPAstimulated HT-1080 cells. Further experiments are needed to clarify this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Novel Antitumor Invasive Actions of <i>p</i>-Cymene by Decreasing MMP-9/TIMP-1 Expression Ratio in Human Fibrosarcoma HT-1080 Cells

Liu

Sato

2016

Biological & Pharmaceutical Bulletin

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p-Cymene (4-isopropyltoluene) has been reported to have beneficial actions such as anti-inflammatory and antinociceptive activities. To evaluate whether p-cymene exhibits antitumor invasive actions, we examined the effects of p-cymene on the production of matrix metalloproteinase 9 (MMP-9)/gelatinase B and tissue inhibitor of metalloproteinases-1 (TIMP-1) in human fibrosarcoma HT-1080 cells. p-Cymene was found to dose-dependently inhibit the 12-O-tetradecanoylphorbol 13-acetate (TPA)-augmented production and gene expression of MMP-9 in HT-1080 cells. In contrast, p-cymene enhanced the TPA-augmented production and gene expression of TIMP-1 in HT-1080 cells. However, there was no change in the constitutive level of MMP-9 and TIMP-1 mRNAs and TIMP-1 protein in p-cymene-treated cells. In addition, we found that the in-vitro TPA-augmented invasiveness of HT-1080 cells was inhibited by p-cymene in a dose-dependent manner. Furthermore, p-cymene was found to suppress the constitutive and/or TPA-augmented phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) in HT-1080 cells. Thus, these results provide novel evidence that p-cymene is an effective candidate for the prevention of tumor invasion and metastasis through mechanisms that include the inhibition of MMP-9 expression and the augmentation of TIMP-1 production along with the suppression of ERK1/2 and p38 MAPK signal pathways in tumor cells.Key words p-cymene; tumor invasion; matrix metalloproteinase 9; tissue inhibitor of metalloproteinases-1; extracellular signal-regulated kinase 1/2 (ERK1/2); p38 mitogen-activated protein kinase (p38 MAPK)The proteolytic degradation of extracellular matrix (ECM) components in basement membranes and stroma tissues is requisite for progressing the invasion and metastasis of malignant tumor cells. Matrix metalloproteinases (MMPs) play a crucial role in ECM degradation, and different sets of MMPs concertedly act in ECM breakdown. 1,2) Gelatinase A (72-kDa type IV collagenase)/MMP-2 and gelatinase B (92-kDa type IV collagenase)/MMP-9 have been reported to facilitate tumor cell invasion and epithelial-mesenchymal transition as a promoter and/or modulator in normal and tumor cells in vivo and in vitro.3) On the other hand, the enzymic activity of MMPs and proteolytic activation of the MMP precursor (proMMP) have been reported to be controlled by endogenous inhibitors such as tissue inhibitors of metalloproteinases (TIMPs).4) Since four TIMPs have been identified, designated as TIMP-1, TIMP-2, TIMP-3, and TIMP-4, they inhibit MMPs by forming a strong noncovalent complex with a 1 : 1 stoichiometry. 4) Regarding the inhibitory properties among the TIMPs, TIMPs can bind to different sets of MMPs: e.g., the preference inhibition of TIMP-1 against MMP-9, MMP-3, and MMP-1, and that of TIMP-2 against MMP-2 rather than MMP-9.4,5) Therefore, the inhibition of expression and/or enzymic activity of MMP is likely to be an effective target(s) for preventing tumor invasion and metastasis.

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p-Cymene Modulates In Vitro and In Vivo Cytokine Production by Inhibiting MAPK and NF-κB Activation

Cited by 47 publications

References 35 publications

Terpenes from Forests and Human Health

Terpenes from Forests and Human Health

Treatment of acne with tea tree oil (melaleuca) products: A review of efficacy, tolerability and potential modes of action

Novel Antitumor Invasive Actions of <i>p</i>-Cymene by Decreasing MMP-9/TIMP-1 Expression Ratio in Human Fibrosarcoma HT-1080 Cells

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