Inhibition of tumor growth by β-elemene through downregulation of the expression of uPA, uPAR, MMP-2, and MMP-9 in a murine intraocular melanoma model

Hong, Seonki; Liu, Lei; Liu, Limin; Geng, Jin; Chen, Lei

doi:10.1097/cmr.0000000000000124

Cited by 27 publications

(23 citation statements)

References 36 publications

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“…The antitumor effect of β-elemene has been demonstrated in multiple types of tumor, particularly in lung cancer treatment, but the underlying mechanism remains unclear (10)(11)(12)(13)(14)(15)(16)(17). Hyperthermia can be a highly effective cancer treatment, particularly when combined with chemotherapy, radiotherapy or immunotherapy (33,34).…”

Section: Discussionmentioning

confidence: 99%

“…It has been used to target multiple types of solid tumor, including lung, esophageal and breast cancers, hepatocarcinoma, glioblastoma and melanoma. β-elemene has been reported to inhibit the growth and DNA synthesis of multiple types of tumor cell, resulting in the apoptosis or suppressed growth of tumors, without severe side effects (10)(11)(12)(13)(14)(15)(16)(17). Hyperthermia is an adjuvant therapeutic modality in cancer treatment, by which the tumor region is maintained at high temperatures in order to inhibit the growth of cancer cells.…”

Section: Introductionmentioning

confidence: 99%

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Anticancer effects of β-elemene with hyperthermia in lung cancer cells

Wang²,

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. β-elemene is a novel, plant-derived anticancer drug, which has been used to target multiple solid tumor types. Hyperthermia is an adjuvant therapeutic modality to treat cancer. However, the underlying mechanisms associated with the efficacy of these two treatments are largely unknown. The aim of the present study was to evaluate the effects of β-elemene combined with hyperthermia in lung cancer cell lines. An MTT assay was used to determine cell viability. The cell cycle and apoptosis were analyzed using flow cytometry. The morphology of cells during apoptosis was determined using a transmission electron microscope. The expression levels of P21, survivin, caspase-9, B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax) mRNA were detected using quantitative polymerase chain reaction. β-elemene with hyperthermia treatment significantly inhibited the viability and increased the apoptosis rate of A549 cells compared with β-elemene treatment alone (P<0.01), and significantly decreased the proportion of cells in S phase compared with the control (P<0.01). Morphological observation using transmission electron microscopy indicated cross-sectional features of apoptosis: Chromatin condensation, reduced integrity of the plasma membrane, increased cellular granularity, nuclear collapse and the formation of apoptotic bodies. β-elemene with hyperthermia treatment significantly promoted P21 and Bax mRNA expression (P<0.01) and significantly decreased caspase-9, Bcl-2 and survivin mRNA expression (P<0.01) in A549 cells. In conclusion, β-elemene with hyperthermia has a significant inhibitory effect on A549 cells. This occurs through reducing S phase and inducing apoptosis, via an increase in P21 and Bax expression and a decrease in caspase-9, Bcl-2 and survivin expression.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Anticancer effects of β-elemene with hyperthermia in lung cancer cells

Wang²,

Zhang

et al. 2017

Experimental and Therapeutic Medicine

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“…They are employed to evaluate the effect of EOs on tumor growth and metastasization, as well as tumor angiogenesis, after subcutaneous or intravenous (lateral tail vein) cell injection [119]. In some cases subretinal, intradermal, intracerebral injection of melanoma cells is employed [38,86,120,121]. Routes of EO administration include oral, intraperitoneal, intravitreal, peritumoral, topical as well as inhalation (fragrant environmental).…”

Section: Mechanism Of Action Of Eos In Melanomamentioning

confidence: 99%

“…Regarding autophagy, some EOs or their components, have been found to affect basal autophagy or to trigger autophagy induced by serum starvation and/or rapamycin in cancer cells from different origin, indicating an mTOR independent mechanism [176]. α-Thujone, D-limonene, terpinel-4-ol and β-elemene are all components of EOs reported to affect in vitro and/or in vivo melanoma growth or melanogenesis [120,131,144,152,177] and to induce autophagy, respectively, in glioblastoma [178], neuroblastoma [179], leukemic [180] and breast carcinoma [181] cells. To the best of our knowledge, no studies exist regarding the ability of these or other EO components to induce autophagy or to affect autophagic flux in melanoma cells.…”

Section: Induction Of Necrosis or Modulation Of Autophagymentioning

confidence: 99%

Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

Martile

Garzoli

Ragno

et al. 2020

Cancers

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The last two decades have seen the development of effective therapies, which have saved the lives of a large number of melanoma patients. However, therapeutic options are still limited for patients without BRAF mutations or in relapse from current treatments, and severe side effects often occur during therapy. Thus, additional insights to improve treatment efficacy with the aim to decrease the likelihood of chemoresistance, as well as reducing side effects of current therapies, are required. Natural products offer great opportunities for the discovery of antineoplastic drugs, and still represent a useful source of novel molecules. Among them, essential oils, representing the volatile fraction of aromatic plants, are always being actively investigated by several research groups and show promising biological activities for their use as complementary or alternative medicine for several diseases, including cancer. In this review, we focused on studies reporting the mechanism through which essential oils exert antitumor action in preclinical wild type or mutant BRAF melanoma models. We also discussed the latest use of essential oils in improving cancer patients’ quality of life. As evidenced by the many studies listed in this review, through their effect on apoptosis and tumor progression-associated properties, essential oils can therefore be considered as potential natural pharmaceutical resources for cancer management.

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“…In addition, a previous study reported that there were no significant changes induced by curcumin in the Wnt/β-catenin pathway (19). β-elemene, another well-known bioactive component, was also found to exhibit antimetastatic properties in melanoma and breast cancer in vitro or in vivo (20,21). Growing evidence shows that furanodiene exerts pro-apoptotic, anti-angiogenic, and antimetastatic effects in several cancer cell lines (22,23).…”

Section: Introductionmentioning

confidence: 99%

Combined effects of furanodiene and doxorubicin on the migration and invasion of MDA-MB-231 breast cancer cells in vitro

et al. 2017

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Furanodiene is one of the major bioactive components isolated from the natural product of the plant, Curcuma wenyujin Y.H. Chen et C. Ling. Furanodiene has been found to exert anticancer effects in various types of cancer cell lines, as well as exhibit antimetastatic activities. However, the antimetastatic capacity of furanodiene in combination with the common chemotherapy drug doxorubicin has not been investigated. We found that doxorubicin at a non-toxic concentration induced cell migration and cell invasion in highly metastatic breast cancer cells. Combinational treatments with furanodiene and doxorubicin blocked the invasion and migration of MDA-MB-231 breast cancer cells in vitro. We also clarified the effects of the combination on the signaling pathways involved in migration, invasion, and cytoskeletal organization. When combined with doxorubicin, furanodiene downregulated the expression of integrin αV and β-catenin and inhibited the phosphorylation of paxillin, Src, focal adhesion kinase (FAK), p85, and Akt. Moreover, combinational treatments also resulted in a decrease in matrix metalloproteinase-9 (MMP-9). Further study demonstrated that the co-treatments with furanodiene did not significantly alter the effects of doxorubicin on the tubulin cytoskeleton, represented by no influence on the expression levels of RhoA, Cdc42, N-WASP, and α/β tubulin. These observations indicate that furanodiene is a potential agent that may be utilized to improve the anticancer efficacy of doxorubicin and overcome the risk of chemotherapy in highly metastatic breast cancer.

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Inhibition of tumor growth by β-elemene through downregulation of the expression of uPA, uPAR, MMP-2, and MMP-9 in a murine intraocular melanoma model

Cited by 27 publications

References 36 publications

Anticancer effects of β-elemene with hyperthermia in lung cancer cells

Anticancer effects of β-elemene with hyperthermia in lung cancer cells

Essential Oils and Their Main Chemical Components: The Past 20 Years of Preclinical Studies in Melanoma

Combined effects of furanodiene and doxorubicin on the migration and invasion of MDA-MB-231 breast cancer cells in vitro

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