β-Elemene enhances the efficacy of gefitinib on glioblastoma multiforme cells through the inhibition of the EGFR signaling pathway

Mu, Lin; Wang, Tianjiao; Chen, Yanwei; Tang, Xueyan; Yuan, Yuhui; Zhao, Yun

doi:10.3892/ijo.2016.3626

Cited by 50 publications

(46 citation statements)

References 38 publications

(37 reference statements)

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“…Similarly, in EGFR-TKI-resistant lung cancer cells with T790M mutation, the combination of a protein kinase CK2 inhibitor and an EGFR-TKI induced a high level of autophagy that degraded EGFR protein and promoted apoptosis [65]. The plant-extracted compound β-elemene can also enhance autophagy and cell death in gefitinib-treated glioblastoma cells [66]. Our recent study demonstrated that EGFR-modulated autophagy under hypoxia plays a dual role in cell survival and cell death in the same cancer cell line [50].…”

Section: Egfr Family Members Regulates Autophagymentioning

confidence: 99%

EGFR Family Members’ Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer

Henson

Chen

Gibson

2017

Cancers

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The epidermal growth factor receptor (EGFR) signaling pathways are altered in many cancers contributing to increased cell survival. These alterations are caused mainly through increased expression or mutation of EGFR family members EGFR, ErbB2, ErbB3, and ErbB4. These receptors have been successfully targeted for cancer therapy. Specifically, a monoclonal antibody against ErbB2, trastuzumab, and a tyrosine kinase inhibitor against EGFR, gefitinib, have improved the survival of breast and lung cancer patients. Unfortunately, cancer patients frequently become resistant to these inhibitors. This has led to investigating how EGFR can contribute to cell survival and how cancer cells can overcome inhibition of its signaling. Indeed, it is coming into focus that EGFR signaling goes beyond a single signal triggering cell proliferation and survival and is a sensor that regulates the cell’s response to microenvironmental stresses such as hypoxia. It acts as a switch that modulates the ability of cancer cells to survive. Autophagy is a process of self-digestion that is inhibited by EGFR allowing cancer cells to survive under stresses that would normally cause death and become resistant to chemotherapy. Inhibiting EGFR signaling allows autophagy to contribute to cell death. This gives new opportunities to develop novel therapeutic strategies to treat cancers that rely on EGFR signaling networks and autophagy. In this review, we summarize the current understanding of EGFR family member regulation of autophagy in cancer cells and how new therapeutic strategies could be developed to overcome drug resistance.

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Section: Egfr Family Members Regulates Autophagymentioning

confidence: 99%

EGFR Family Members’ Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer

Henson

Chen

Gibson

2017

Cancers

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“…The current research shows that β-elemene has the effects to induce cell apoptosis and differentiation, with reverse multiple drug resistance of tumor, and enhance sensibilization of combined radiotherapy and chemotherapy etc (2). Moreover, its toxic and side effects are very few (2). At present, it has been widely applied in the clinical treatment of liver cancer, lung cancer, breast cancer, cervical cancer, gastrointestinal tumor, carcinoma of urinary bladder, brain tumor and other superficial tumors, such as bladder cancer and gland cancer (3).…”

Section: Introductionmentioning

confidence: 99%

“…The main active component is β-elemene. The current research shows that β-elemene has the effects to induce cell apoptosis and differentiation, with reverse multiple drug resistance of tumor, and enhance sensibilization of combined radiotherapy and chemotherapy etc (2). Moreover, its toxic and side effects are very few (2).…”

Section: Introductionmentioning

confidence: 99%

β-elemene enhances anticancer and anti-metastatic effects of osteosarcoma of ligustrazine inï¿½vitro and inï¿½vivo

et al. 2018

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Abstract. The present study aimed to determine the anticancer effects of the combination of β-elemene and ligustrazine in vitro as well as in in vivo. Following evaluation using an MTT assay, β-elemene, ligustrazine and the β-elemene-ligustrazine combination treatments all exhibited the capacity to inhibit the growth of OS-732 cells, with inhibitory rates of 43.3, 54.4, and 75.0%, respectively. Using a flow cytometry assay, it was determined that the β-elemene-ligustrazine combination possessed the highest apoptotic rate (30.6%). Furthermore, β-elemene-ligustrazine combination treatment resulted in the highest downregulation of G protein-coupled receptor 124, vascular endothelial growth factor, matrix metallopeptidase (MMP)-2 and MMP-9 mRNA, and protein expression levels. In addition, the combined treatment led to an increase in the mRNA and protein expression of endostatin, TIMP metallopeptidase inhibitor (TIMP)-1 and TIMP-2 in OS-732 cells. Additionally, β-elemene-ligustrazine caused a decrease in nuclear factor-κB, interleukin-8, C-X-C motif chemokine receptor 4 and urokinase-type plasminogen activator mRNA expression, as well as an increase in caspase-3, caspase-8, and caspase-9 mRNA expression. In vivo, the β-elemene-ligustrazine combination was able to reduce the weight and the bulk of the tumor in BALB/c-nu/nu nude mice compared with any other group. All the results described above regarding changes to mRNA and protein expression were further confirmed in vivo in the tumor tissue of mice. The results of the present study have suggested that the combination of β-elemene-ligustrazine exhibits greater anticancer effects compared with β-elemeneor ligustrazine-alone treatment.

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“…Beta‐elemene (β‐elemene), a major non‐cytotoxic anticancer ingredient isolated from Curcuma Zedoary , can induce cancer cell apoptosis, cell cycle arrest, and enhance the sensitivity of radiotherapy and chemotherapy without myelosuppression and obvious damages to liver and kidney . β‐Elemene has already been approved by China food and drug administration (CFDA) to against cancer in clinic, in combination with chemotherapeutic drugs.…”

Section: Introductionmentioning

confidence: 99%

Beta‐elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation

Pan

Wang

Huang

et al. 2019

J Cellular Molecular Medi

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Pyruvate kinase M2 (PKM2), playing a central role in regulating aerobic glycolysis, was considered as a promising target for cancer therapy. However, its role in cancer metastasis is rarely known. Here, we found a tight relationship between PKM2 and breast cancer metastasis, demonstrated by the findings that beta‐elemene (β‐elemene), an approved drug for complementary cancer therapy, exerted distinct anti‐metastatic activity dependent on PKM2. The results indicated that β‐elemene inhibited breast cancer cell migration, invasion in vitro as well as metastases in vivo. β‐Elemene further inhibited the process of aerobic glycolysis and decreased the utilization of glucose and the production of pyruvate and lactate through suppressing pyruvate kinase activity by modulating the transformation of dimeric and tetrameric forms of PKM2. Further analysis revealed that β‐elemene suppressed aerobic glycolysis by blocking PKM2 nuclear translocation and the expression of EGFR, GLUT1 and LDHA by influencing the expression of importin α5. Furthermore, the effect of β‐elemene on migration, invasion, PKM2 transformation, and nuclear translocation could be reversed in part by fructose‐1,6‐bisphosphate (FBP) and L‐cysteine. Taken together, tetrameric transformation and nuclear translocation of PKM2 are essential for cancer metastasis, and β‐elemene inhibited breast cancer metastasis via blocking aerobic glycolysis mediated by dimeric PKM2 transformation and nuclear translocation, being a promising anti‐metastatic agent from natural compounds.

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β-Elemene enhances the efficacy of gefitinib on glioblastoma multiforme cells through the inhibition of the EGFR signaling pathway

Cited by 50 publications

References 38 publications

EGFR Family Members’ Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer

EGFR Family Members’ Regulation of Autophagy Is at a Crossroads of Cell Survival and Death in Cancer

β-elemene enhances anticancer and anti-metastatic effects of osteosarcoma of ligustrazine inï¿½vitro and inï¿½vivo

Beta‐elemene inhibits breast cancer metastasis through blocking pyruvate kinase M2 dimerization and nuclear translocation

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