Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation

Chen, Peng; Li, Xuejie; Zhang, Ruonan; Liu, Shuiping; Yu, Xiang; Zhang, Mingming; Chen, Xiaying; Pan, Ting; Yan, Lili; Jiao, Feng; Duan, Ting; Wang, Da; Bi, Cheng; Jin, Tengchuan; Wang, Wengang; Chen, Liuxi; Huang, Xingxing; Zhang, Wenzheng; Sun, Yitian; Li, Guohua; Kong, Lingpan; Chen, Xiaohui; Li, Yongqiang; Yang, Zaixing; Zhang, Qin; Zhuo, Lvjia; Sui, Xinbing; Xie, Tian

doi:10.7150/thno.44705

Cited by 263 publications

(195 citation statements)

References 18 publications

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“…Chen et al found b-elemene is a unique natural ferroptosis inducer. b-elemene and cetuximab, which were combined to treat KRAS mutant CRC cells, could induce ferroptosis (Chen et al, 2020). Shen et al demonstrated that RB could inactivate GPX4 to trigger ferroptosis in CRC cells, which can inhibit the growth of CRC cells and tumor formation (Shen et al, 2020).…”

Section: Colorectal Carcinomamentioning

confidence: 99%

“…In the experiments of Ma et al, Siramesine and lapatinib can be used synergistically to induce an increase in iron levels and trigger ferroptosis (Ma S. et al, 2017). In addition to some commonly used ferroptosis drugs, some natural compounds such as Vitamin E (Ma S. et al, 2017), Baicalein (Xie et al, 2016), b-elemene (Chen et al, 2020), gallic acid (Khorsandi et al, 2020) can regulate ferroptosis by affecting the level of lipid peroxidation. At present, one of the main methods used in tumor treatment is chemotherapy, which is mainly to inhibit the synthesis of DNA or RNA at different stages of tumor growth and spread to inhibit the abnormal proliferation of tumors.…”

Section: Othersmentioning

confidence: 99%

“…found β-elemene is a unique natural ferroptosis inducer. β-elemene and cetuximab, which were combined to treat KRAS mutant CRC cells, could induce ferroptosis ( Chen et al., 2020 ). Shen et al.…”

Section: The Link Between Ferroptosis and Cancermentioning

confidence: 99%

“…In the experiments of Ma et al., Siramesine and lapatinib can be used synergistically to induce an increase in iron levels and trigger ferroptosis ( Ma S. et al., 2017 ). In addition to some commonly used ferroptosis drugs, some natural compounds such as Vitamin E ( Ma S. et al., 2017 ), Baicalein ( Xie et al., 2016 ), β-elemene ( Chen et al., 2020 ), gallic acid ( Khorsandi et al., 2020 ) can regulate ferroptosis by affecting the level of lipid peroxidation.…”

Section: Current Status Of Research On Ferroptosis Treatmentmentioning

confidence: 99%

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The Mechanism of Ferroptosis and Applications in Tumor Treatment

et al. 2020

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Iron-dependent ferroptosis is a new form of cell death in recent years, which is driven by lipid peroxidation. The lethal lipid accumulation caused by glutathione depletion or inactivation of glutathione peroxidase 4 (GPX4) is characteristic of the ferroptosis process. In recent years, with the in-depth study of ferroptosis, various types of diseases have been reported to be related to ferroptosis. In other words, ferroptosis, which has attracted widespread attention in the fields of biochemistry, oncology, and especially materials science, can undoubtedly provide a new way for patients. This review introduces the relevant mechanisms of ferroptosis, the relationship between ferroptosis and various cancers, as well as the application of ferroptosis in tumor treatment. We also sorted out the genes and drugs that regulate ferroptosis. Moreover, small molecule compound-induced ferroptosis has a strong inhibitory effect on tumor growth in a drugresistant environment, which can enhance the sensitivity of chemotherapeutic drugs, suggesting that ferroptosis is very important in the treatment of tumor drug resistance, but the details are still unclear. How to use ferroptosis to fight cancer, and how to prevent drug-resistant tumor cells have become the focus and direction of research. At the end of the article, some existing problems related to ferroptosis are summarized for future research.

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Section: Colorectal Carcinomamentioning

confidence: 99%

Section: Othersmentioning

confidence: 99%

Section: The Link Between Ferroptosis and Cancermentioning

confidence: 99%

Section: Current Status Of Research On Ferroptosis Treatmentmentioning

confidence: 99%

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The Mechanism of Ferroptosis and Applications in Tumor Treatment

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“…在乳腺癌中, 榄香烯通过重塑雌激素受体α(ERα)的表达逆转乳腺癌细胞对他莫昔芬的耐药 [54] ; 同时可通过外泌体降低耐药传递逆转乳腺癌的多药耐药 [55] . 在大肠癌中, 榄香烯可以通过诱导铁死亡和抑制上皮-间质转化(epithelial-mesenchymal transitions, EMT)增强KRAS突变型大肠癌对西妥昔单抗的敏感性, 为KRAS突变型大肠癌患者的治疗提供一种新的策略 [56] . 在神经系统肿瘤中, 榄香烯通过抑制 EGFR信号通路可增强吉非替尼对神经胶质瘤的敏感性 [57] .…”

Section: 腺癌患者治疗效果和预后的重要因素近几年针对乳腺癌内分泌治疗耐药的机制研究取得较大进展 Pi3k/unclassified

Combination of Chinese and western medicine to prevent and reverse resistance of cancer cells to anticancer drugs

Zhang

Huang

et al. 2020

Chin. Sci. Bull.

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Arsenene Nanodots with Selective Killing Effects and their Low‐Dose Combination with ß‐Elemene for Cancer Therapy

et al. 2021

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Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence‐change of arsenic (from less toxic As0 to severely toxic oxidation states), followed by decreased superoxide dismutase activity and massive reactive oxygen species (ROS) production. These effects occur selectively within cancer cells, causing mitochondrial damage, cell‐cycle arrest, and DNA damage. Moreover, AsNDs@PEG when applied in a multi‐drug combination strategy with β‐elemene, a plant‐derived anticancer drug, achieves synergistic antitumor outcomes, and its newly discovered on‐demand photothermal properties facilitate the elimination of the tumors without recurrence, potentially further expanding its clinical utility. In line of the practicability for a large‐scale fabrication and negligible systemic toxicity of AsNDs@PEG (even at high doses and with repetitive administration), a new‐concept arsenical drug with high therapeutic efficacy for selective solid tumor therapy is provided.

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Combinative treatment of β-elemene and cetuximab is sensitive to KRAS mutant colorectal cancer cells by inducing ferroptosis and inhibiting epithelial-mesenchymal transformation

Cited by 263 publications

References 18 publications

The Mechanism of Ferroptosis and Applications in Tumor Treatment

The Mechanism of Ferroptosis and Applications in Tumor Treatment

Combination of Chinese and western medicine to prevent and reverse resistance of cancer cells to anticancer drugs

Arsenene Nanodots with Selective Killing Effects and their Low‐Dose Combination with ß‐Elemene for Cancer Therapy

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