β-Elemene Enhances the Sensitivity of Osteosarcoma Cells to Doxorubicin via Downregulation of Peroxiredoxin-1

Zhang, Shaochun; Guo, Weichun

doi:10.2147/ott.s303152

Cited by 9 publications

(5 citation statements)

References 39 publications

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“…In similar in vivo studies, AUR alone has been found to be ineffective in treating various cancers and is being evaluated in combination with other chemotherapeutic or oxidative stress-inducing agents (18)(19)(20). Doxorubicin, a key drug used in the chemotherapy of OS, has also been shown to induce oxidative stress (21). The evaluation of the combination of AUR and doxorubicin for suppressing local progression of OS should be considered.…”

Section: Discussionmentioning

confidence: 99%

The Thioredoxin Reductase Inhibitor Auranofin Suppresses Pulmonary Metastasis of Osteosarcoma, But Not Local Progression

et al. 2021

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Background/Aim: Auranofin (AUR), a thioredoxin reductase (TXNRD) inhibitor, shows anticancer activity against several cancers. This study investigated the effects of AUR on the local progression and pulmonary metastasis of osteosarcoma (OS). Materials and Methods: Publicly available expression cohorts were analysed to study the relationship between TXNRD-2 expression and the survival of patients with OS. The murine OS cell line LM8 was stimulated with AUR. Cell viability, apoptosis-related protein levels, caspase activity, and wound healing were analysed. Tumor progression and pulmonary metastasis were investigated in C3H mice implanted with LM8 cells. Results: High-level expression of TXNRD-2 represented a negative prognostic factor for metastasis and overall survival in patients with OS. AUR induced apoptosis of OS cells via the oxidative stress-MAPK-Caspase 3 pathway, and suppressed the migration of OS cells. AUR inhibited the pulmonary metastasis of OS, but not local progression. Conclusion: AUR represents a potential therapeutic drug for suppressing pulmonary metastasis of OS.Osteosarcoma (OS) is a relatively rare malignant tumor with a high incidence in the adolescent and young adult population, and is associated with poor survival. Treatment of OS includes surgery and perioperative chemotherapies (1). Standard chemotherapy for pediatric patients involves the use of doxorubicin, cisplatin, and high-dose methotrexate. However, the five-year survival probability for OS is poor, and it is worse for patients with pulmonary metastases. Chemotherapies used at present include conventional cytotoxic agents with strong side effects; therefore, the development of novel therapeutic agents is desirable. The oxidation-reduction (redox) system is an essential regulator of various metabolic functions of the cell. Thioredoxin (TXN), a key molecule in the redox system, plays an active role in scavenging reactive oxygen species (ROS), which are associated with the development of several diseases, including cancers and sarcomas (2, 3). ROS has been shown to activate mitogen-activated protein kinases (MAPKs), such as p38 and c-Jun N-terminal kinase (JNK), and induce apoptosis in cancer cells (4). TXN reductases (TXNRDs) are enzymes that catalyse the reduction of TXN and regulate TXN activity. Members of the TXNRD family comprise three isoforms including cytosolic TXNRD-1, mitochondrial TXNRD-2, and TXNRD-3. TXNRD-2 has been reported to be often overexpressed in cancer cells thereby conferring resistance to apoptosis (5); TXNRDs represent therapeutic targets of several cancers (6). Auranofin (AUR) is an anti-rheumatic drug approved by the US Food and Drug Administration (FDA) that functions as a TXNRD inhibitor and has anticancer properties against several cancers (7, 8). The effect of AUR alone on local progression and pulmonary metastases of OS has not been reported in previous studies. Therefore, we investigated the effects of AUR on local progression and pulmonary metastasis of OS in vitro and in vivo. Materials and Methods...

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Section: Discussionmentioning

confidence: 99%

The Thioredoxin Reductase Inhibitor Auranofin Suppresses Pulmonary Metastasis of Osteosarcoma, But Not Local Progression

et al. 2021

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“…One of the advantages of co-loading natural active ingredients with chemotherapy drugs is to reverse MDR. Many natural components, such as resveratrol (RES) (Zhang et al., 2016b ), tetrandrine (TET) (Liao et al., 2019 ; Li et al., 2020e ), epigallocatechin gallate (EGCG) (Cheng et al., 2016 ), pachymaric acid and dehydrotudouic acid (PT) (Li et al., 2020f ), quinine hydrochloride (QN) (Shen & Qiu, 2017 ), β-ELE (Zhang & Guo, 2021 ), ferulic acid (FA) (Muthusamy et al., 2016 ), naringin (Jabri et al., 2019 ), baicalein (BCL) (Li et al., 2018b ), Que (Lu et al., 2020b ) and Sch B (Wang et al., 2017 ), could inhibit MDR by inhibiting the ABC transport, including P-gp, BCRP, ABCB1, etc. In addition, natural components can also inhibit MDR effects by inhibiting epithelial-mesenchymal transition through other pathways, such as RES (Buhrmann et al., 2015 ; Xu et al., 2017b ), EGCG (Yuan et al., 2017 ) and BCL (Yu et al., 2017 ).…”

Section: The Effect Of Natural Active Ingredients Combined With Chemo...mentioning

confidence: 99%

Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review

Shao

et al. 2022

Drug Delivery

127

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Chemotherapy drugs have been used for a long time in the treatment of cancer, but serious side effects are caused by the inability of the drug to be solely delivered to the tumor when treating cancer with chemotherapy. Natural products have attracted more and more attention due to the antitumor effect in multiple ways, abundant resources and less side effects. Therefore, the combination of natural active ingredients and chemotherapy drugs may be an effective antitumor strategy, which can inhibit the growth of tumor and multidrug resistance, reduce side effects of chemotherapy drugs. Nano-drug co-delivery system (NDCDS) can play an important role in the combination of natural active ingredients and chemotherapy drugs. This review provides a comprehensive summary of the research status and application prospect of nano-delivery strategies for the combination of natural active ingredients and chemotherapy drugs, aiming to provide a basis for the development of anti-tumor drugs.

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“…In oral squamous cell carcinoma cells, βelemene has been demonstrated to alleviate cisplatin resistance both in vitro and in vivo by targeting the JAK2/STAT3 pathway [18]. Additionally, β-elemene increases the sensitivity of osteosarcoma cells to doxorubicin by suppressing peroxiredoxin-1 [19]. In gastric cancer, β-elemene impedes the metastasis of multidrug-resistant cells through modulation of the miR-1323/Cbl-b/EGFR pathway [20].…”

Section: Introductionmentioning

confidence: 99%

β-Elemene Reverses Gefitinib Resistance in NSCLC Cells by Inhibiting lncRNA H19-Mediated Autophagy

Zhang,

Zheng,

Zhu

et al. 2024

Pharmaceuticals

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Lung cancer is a leading cause of mortality worldwide, especially among Asian patients with non-small cell lung cancer (NSCLC) who have epidermal growth factor receptor (EGFR) mutations. Initially, first-generation EGFR tyrosine kinase inhibitors (TKIs) are commonly administered as the primary treatment option; however, encountering resistance to these medications poses a significant obstacle. Hence, it has become crucial to address initial resistance and ensure continued effectiveness. Recent research has focused on the role of long noncoding RNAs (lncRNAs) in tumor drug resistance, especially lncRNA H19. β-elemene, derived from Curcuma aromatic Salisb., has shown strong anti-tumor effects. However, the relationship between β-elemene, lncRNA H19, and gefitinib resistance in NSCLC is unclear. This study aims to investigate whether β-elemene can enhance the sensitivity of gefitinib-resistant NSCLC cells to gefitinib and to elucidate its mechanism of action. The impact of gefitinib and β-elemene on cell viability was evaluated using the cell counting kit-8 (CCK8) assay. Furthermore, western blotting and qRT-PCR analysis were employed to determine the expression levels of autophagy-related proteins and genes, respectively. The influence on cellular proliferation was gauged through a colony-formation assay, and apoptosis induction was quantified via flow cytometry. Additionally, the tumorigenic potential in vivo was assessed using a xenograft model in nude mice. The expression levels of LC3B, EGFR, and Rab7 proteins were examined through immunofluorescence. Our findings elucidate that the resistance to gefitinib is intricately linked with the dysregulation of autophagy and the overexpression of lncRNA H19. The synergistic administration of β-elemene and gefitinib markedly attenuated the proliferative capacity of resistant cells, expedited apoptotic processes, and inhibited the in vivo proliferation of lung cancer. Notably, β-elemene profoundly diminished the expression of lncRNA H19 and curtailed autophagic activity in resistant cells, thereby bolstering their responsiveness to gefitinib. Moreover, β-elemene disrupted the Rab7-facilitated degradation pathway of EGFR, facilitating its repositioning to the plasma membrane. β-elemene emerges as a promising auxiliary therapeutic for circumventing gefitinib resistance in NSCLC, potentially through the regulation of lncRNA H19-mediated autophagy. The participation of Rab7 in this dynamic unveils novel insights into the resistance mechanisms operative in lung cancer, paving the way for future therapeutic innovations.

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β-Elemene Enhances the Sensitivity of Osteosarcoma Cells to Doxorubicin via Downregulation of Peroxiredoxin-1

Cited by 9 publications

References 39 publications

The Thioredoxin Reductase Inhibitor Auranofin Suppresses Pulmonary Metastasis of Osteosarcoma, But Not Local Progression

The Thioredoxin Reductase Inhibitor Auranofin Suppresses Pulmonary Metastasis of Osteosarcoma, But Not Local Progression

Nano-drug co-delivery system of natural active ingredients and chemotherapy drugs for cancer treatment: a review

β-Elemene Reverses Gefitinib Resistance in NSCLC Cells by Inhibiting lncRNA H19-Mediated Autophagy

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