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

Li, JingZhe; Liu, Changzhen; Sato, Takashi

doi:10.1248/bpb.b15-00827

Cited by 22 publications

(13 citation statements)

References 32 publications

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“…The anti-inflammatory activity of p-cymene at least partly justifies its antinociceptive activity, as recorded in several in vivo studies performed on murine model systems [ 8 , 10 , 11 ]. Moreover, recent investigations report the antitumor activity of p-cymene and metal p-cymene complexes such as rutenium (II)- and osmium (II)-p-cymene complexes, which inhibit tumor proliferation through an antiangiogenic mechanism, cancer cell cytotoxicity, and anti-adhesion activity [ 12 , 13 , 14 ]. p-Cymene is the main antimicrobial compound in thyme, and a large body of evidence suggests that this monoterpene possesses antibacterial, antiviral and antifungal activities.…”

Section: Introductionmentioning

confidence: 99%

Update on Monoterpenes as Antimicrobial Agents: A Particular Focus on p-Cymene

et al. 2017

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p-Cymene [1-methyl-4-(1-methylethyl)-benzene] is a monoterpene found in over 100 plant species used for medicine and food purposes. It shows a range of biological activity including antioxidant, anti-inflammatory, antinociceptive, anxiolytic, anticancer and antimicrobial effects. This last property has been widely investigated due to the urgent need for new substances with antimicrobial properties, to be used to treat communicable diseases whose diffusion in developed countries has been facilitated by globalization and the evolution of antimicrobial resistance. This review summarizes available scientific data, as reported by the most recent studies describing the antimicrobial activity of p-cymene either alone, or as the main component of plant extracts, as well as addressing the mechanisms of action of cymenes as antimicrobial agents. While p-cymene is one of the major constituents of extracts and essential oils used in traditional medicines as antimicrobial agents, but considering the limited data on its in vivo efficacy and safety, further studies are required to reach a definitive recommendation on the use and beneficial effects of p-cymene in human healthcare and in biomedical applications as a promising candidate to functionalize biomaterials and nanomaterials.

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Section: Introductionmentioning

confidence: 99%

Update on Monoterpenes as Antimicrobial Agents: A Particular Focus on p-Cymene

et al. 2017

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“…The differences between the IC 50 values of F-PSEO and L-PSEO are attributed to both compositional and quantitative variations among these oils. The cyclic monoterpene p -cymene, that constitutes a 27.76% (by SPME, 1.33% by hydrodistillation) of the flower oil compared to 5.56% (SPME, 0.1%-hydrodistillation) in L-PSEO, has been reported to exhibit strong antitumor invasive and metastatic actions towards the human fibrosarcoma HT-1080 cells through inhibition of matrix metalloproteinase 9 (MMP-9) along with the suppression of ERK1/2 and p38 MAPK [50]. The cyclic monoterpene α-phellandrene, comprises 13.59% (SPME, 1.74%-hydrodistillation, compared to 1.08% and 0.36% in L-PSEO, respectively), induces apoptosis through the mitochondria-dependent pathway, cell cycle arrest at G0/G1 phase and production of reactive oxygen species (ROS) in murine WEHI-3 leukemic cells [51].…”

Section: Discussionmentioning

confidence: 99%

“…This is particularly obvious with the finding that the general caspase-inhibitor is only able to reverse ∼30% of the oil induced apoptosis in MDA-MB-2 31 compared to ∼60% in MCF-7 cells. The fact that the essential oils of P. spinosa contain compounds that promote cell death by autophagy [53], activation of MAPKs [50], production of ROS [51] and cell cycle arrest [51], proposes that they may also contribute to the cytotoxicity of F-PSEO and L-PSEO.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Analysis of the Chemical Composition and In Vitro Cytotoxic Mechanisms of Pallines Spinosa Flower and Leaf Essential Oils Against Breast Cancer Cells

Saleh

Al–Qudah

Rizvi

et al. 2017

Cell Physiol Biochem

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Background/Aims: In our quest for new natural anticancer agents, we studied the cytotoxicity of the essential oils extracted from flowers and leaves of Pallines spinosa. Methods: The essential oils were extracted by hydrodistillation and solid phase microextraction (SPME) from flowers and leaves of the plant and their composition was determined by GC/GC-MS. The cytotoxicity of the oils was evaluated against MCF-7 and MDA-MB-231 breast adenocarcinomas, and the non-cancerous MCF-10-2A cells, using a flow cytometry-based assay Apoptosis was evaluated by flow cytometry, nuclear staining, caspases activation, and Western blotting techniques, and cell cycle by measuring DNA contents. Results: The hydrodistilled flower oil contained mainly sesquiterpenes (96.39%), while the leaf sample was dominated by oxygenated-sesquiterpenes (51.60%) and sesquiterpene-hydrocarbons (34.06%). In contrast, the SPME oil contained mainly monoterpene-hydrocarbons (44.09%) and sesquiterpene-hydrocarbons (34.15%) in the flower and leaf samples, respectively. The cytotoxicity of the flower oil against MCF-7 (IC₅₀ 0.25 ± 0.03 µg/mL) and MDA-MB-231 (IC₅₀ 0.21 ± 0.03 µg/mL) was much stronger than the leaf oil (IC₅₀ 2.4 ± 0.5 µg/mL and 1.5 ± 0.1 µg/mL, respectively). The toxicity of the flower oil was ∼5 to 8-times less in normal MCF-10-2A (IC₅₀ 1.3 ± 0.2 µg/mL) and blood mononuclear cells (2.80 ± 0.45 µg/mL) as compared to breast and hematological cancer cells, respectively. Both oils induced a caspase-dependent and -independent apoptosis in MCF-7 and MDA-MB-231 cells, and altered the levels of Bcl-2 and Bax proteins. In addition, the oils arrested cell cycle in both cancer cell lines at G0/G1 phase by modulating the expression of cyclin D1, CDK4 and p21 proteins. Conclusion: The cytotoxicity of P. spinosa oils were mediated by apoptosis and cell cycle arrest, suggesting the potential use of their bioactive compounds as natural anticancer compounds.

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“…The movement-evoked pain test did not show significant inhibition in the reduction of paw utilization by the mice (supplementary material). However, another study (Li et al, 2016) demonstrated that PC has the antitumor effect due to the modulation of ERK1/2 and p38 MAPK signal pathways in tumor cells.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

p-Cymene attenuates cancer pain via inhibitory pathways and modulation of calcium currents

et al. 2019

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Background: Oncological pain is one of the most prevalent and difficult-to-treat symptoms in patients with cancer. p-cymene (PC) is a monoterpene found in more than 100 different plant species, endowed with various pharmacological properties-particularly antinociceptive. Hypothesis/Purpose: PC has antinociceptive effect in a model of oncologic pain due to the activation of the descending inhibitory pathway of pain. Study Design: A pre-clinical, longitudinal, blind and randomized study. Methods: Male Swiss mice were induced with S180 cells in the right hind paw, then treated daily with PC (12.5, 25 and 50 mg/kg, s.c.) and screened for mechanical hyperalgesia, spontaneous nociception, nociception induced by non-noxious palpation, tumor growth, changes in the neuromuscular function and existence of bone degradation in the tumor area. The effect of PC on Ca 2+ currents (electrophysiological records), histological and neurochemical changes (immunofluorescence for Fos) were also evaluated. Results: PC reduced (p < 0.05) the mechanical hyperalgesia, the spontaneous (p < 0.001) and non-noxious palpation (p < 0.001) nociceptions, not changing the tumor development, neuromuscular function or histopathological aspects of the paw affected. PC reduced Fos expression in the spinal cord (p < 0.001) and increased this expression in the PAG (p < 0.05) and in the NRM (p < 0.01). PC decreased the density of calcium channel currents (p < 0.05). Conclusion: These results suggest the antinociceptive effect of PC on oncologic pain, probably acting in both ascending and descending pain pathways, and modulating the calcium channel currents in order to exert its effects.

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

Cited by 22 publications

References 32 publications

Update on Monoterpenes as Antimicrobial Agents: A Particular Focus on p-Cymene

Update on Monoterpenes as Antimicrobial Agents: A Particular Focus on p-Cymene

Comprehensive Analysis of the Chemical Composition and In Vitro Cytotoxic Mechanisms of Pallines Spinosa Flower and Leaf Essential Oils Against Breast Cancer Cells

p-Cymene attenuates cancer pain via inhibitory pathways and modulation of calcium currents

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