A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress

Hu, Xinying; Zhang, Zuo-yan; Wu, Liquan; Zeng, Ling‐Hui; Chen, Hui; Zhu, Huajian; Zhang, Jiankang; Shao, Jiaan; Zhang, Chong; Li, Yang-ling; Lin, Nengming

doi:10.1016/j.phymed.2020.153189

Cited by 9 publications

(9 citation statements)

References 27 publications

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“…Additionally, our results showed that CHOP knockdown attenuated the cytotoxicity activity of IATL and cisplatin. Recent studies showed that ROS have emerged as a crucial regulator of ER stress-induced apoptosis in cancer cells (Zhao et al, 2019;Hu et al, 2020). Our findings showed that pretreatment with NAC significantly blocked the combined treatment-induced increase in the expression levels of p-eIF2α, ATF4, and CHOP, suggesting that ER stress activation induced by the combination of IATL and cisplatin is dependent on intracellular ROS accumulation.…”

Section: Discussionsupporting

confidence: 54%

Isoalantolactone Increases the Sensitivity of Prostate Cancer Cells to Cisplatin Treatment by Inducing Oxidative Stress

Huang

et al. 2021

Front. Cell Dev. Biol.

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Prostate cancer is the most common malignancy among men worldwide. Platinum (II)-based chemotherapy has been used to treat a number of malignancies including prostate cancer. However, the potential of cisplatin for treating prostate cancer is restricted owing to its limited efficacy and toxic side effects. Combination therapies have been proposed to increase the efficacy and reduce the toxic side effects. In the present study, we investigated how isoalantolactone (IATL), a sesquiterpene lactone extracted from the medicinal plant Inula helenium L., acts synergistically with cisplatin on human prostate cancer cells. We show that IATL significantly increased cisplatin-induced growth suppression and apoptosis in human prostate cancer cells. Mechanistically, the combined treatment resulted in an excessive accumulation of intracellular reactive oxygen species (ROS), which leads to the activation of endoplasmic reticulum (ER) stress and the JNK signaling pathway in human prostate cancer cells. Pretreatment of cells with the ROS scavenger N-acetylcysteine (NAC) significantly abrogated the combined treatment-induced ROS accumulation and cell apoptosis. In addition, the activation of ER stress and the JNK signaling pathway prompted by IATL and cisplatin was also reversed by NAC pretreatment. In vivo, we found that IATL combined with cisplatin showed the strongest antitumor effects compared with single agents. These results support the notion that IATL and cisplatin combinational treatment may be more effective for treating prostate cancer than cisplatin alone.

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Section: Discussionsupporting

confidence: 54%

Isoalantolactone Increases the Sensitivity of Prostate Cancer Cells to Cisplatin Treatment by Inducing Oxidative Stress

Huang

et al. 2021

Front. Cell Dev. Biol.

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“…Abundant herbal monomers combined with osimertinib had the effect of delaying drug resistance. The mechanisms involved included tumor stem cell inhibition, regulation of reactive oxygen species, and alteration of downstream pathways ( Hu et al, 2020 ; Lai et al, 2021 ). In contrast, research on herbal formulas remains at blurred stages.…”

Section: Discussionmentioning

confidence: 99%

“…Several recent studies have investigated the effects of Chinese herbal compounds on EGFR-TKI resistance ( Hu et al, 2020 ; Tan et al, 2020 ). Feiyanning Formula (FYN) is an anti-cancer formula consisting of Astragalus membranaceus, Ganoderma lucidum, Paris polyphylla, and other Chinese herbs.…”

Section: Introductionmentioning

confidence: 99%

Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway

et al. 2022

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Feiyanning Formula (FYN), a Chinese herbal formula derived from summarized clinical experience, is proven to have anti-tumor effects in lung cancer patients. Osimertinib, a third-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI), can improve progression-free survival and overall survival of patients but drug resistance is inevitable. The current study evaluated the effects of FYN in osimertinib-resistant HCC827OR and PC9OR cells. FYN preferentially inhibited the proliferation and migration of HCC827OR and PC9OR cells. Moreover, FYN and osimertinib exhibited synergistic inhibitory effects on proliferation and migration. Real-time qPCR (RT-qPCR) and western blotting results indicated that FYN downregulated gene and protein levels of GSK3β and SRFS1, which are enriched in the Wnt/β-catenin pathway. Besides, FYN inhibited tumor growth and exhibited synergistic effects with osimertinib in vivo. Collectively, the results suggested that FYN exerted an anti-osimertinib resistance effect via the Wnt/β-catenin pathway.

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“…The administration of drugs was reported to be significantly restricted by their limited therapeutic effect ( 67 ), adverse drug reaction ( 68 ), acquired drug resistance ( 69 ) and so on. Natural products were thus reported capable of (a) enhancing drug efficacy via augmenting its sensitivity ( 44 , 45 ) or achieving therapeutic synergy ( 46 , 47 ), (b) decreasing adverse drug reactions ( 48 , 49 ) and (c) reversing drug resistance ( 50 , 51 ). To have such valuable data about NP-based regulations in this database, the improved therapeutic effects of NP on their corresponding drug were reviewed and explicitly described in NPCDR.…”

Section: Factual Content and Data Retrievalmentioning

confidence: 99%

“…First, a number of clinically important drugs were collected from DrugBank ( 42 ) and TTD ( 43 ), and a systematic literature review on the NPs that were reported to combine with these drugs was conducted. As a result, the collected NP-based drug combinations (as shown in Figure 1 ) were found to (a) enhance drug efficacy by augmenting drug sensitivity ( 44 , 45 ) and achieving therapeutic synergy ( 46 , 47 ), (b) decrease the adverse drug reaction ( 48 , 49 ) and (c) reverse drug resistance ( 50 , 51 ). Second, the molecules or pathways regulated by these collected combinations were manually identified by additional literature review, and their regulation profiles (expression up/down-regulation, increased/decreased phosphorylation, etc.)…”

Section: Introductionmentioning

confidence: 99%

NPCDR: natural product-based drug combination and its disease-specific molecular regulation

Sun

Zhang

Zhou

et al. 2021

Nucleic Acids Research

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Natural product (NP) has a long history in promoting modern drug discovery, which has derived or inspired a large number of currently prescribed drugs. Recently, the NPs have emerged as the ideal candidates to combine with other therapeutic strategies to deal with the persistent challenge of conventional therapy, and the molecular regulation mechanism underlying these combinations is crucial for the related communities. Thus, it is urgently demanded to comprehensively provide the disease-specific molecular regulation data for various NP-based drug combinations. However, no database has been developed yet to describe such valuable information. In this study, a newly developed database entitled ‘Natural Product-based Drug Combination and Its Disease-specific Molecular Regulation (NPCDR)’ was thus introduced. This database was unique in (a) providing the comprehensive information of NP-based drug combinations & describing their clinically or experimentally validated therapeutic effect, (b) giving the disease-specific molecular regulation data for a number of NP-based drug combinations, (c) fully referencing all NPs, drugs, regulated molecules/pathways by cross-linking them to the available databases describing their biological or pharmaceutical characteristics. Therefore, NPCDR is expected to have great implications for the future practice of network pharmacology, medical biochemistry, drug design, and medicinal chemistry. This database is now freely accessible without any login requirement at both official (https://idrblab.org/npcdr/) and mirror (http://npcdr.idrblab.net/) sites.

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A natural anthraquinone derivative shikonin synergizes with AZD9291 against wtEGFR NSCLC cells through reactive oxygen species-mediated endoplasmic reticulum stress

Cited by 9 publications

References 27 publications

Isoalantolactone Increases the Sensitivity of Prostate Cancer Cells to Cisplatin Treatment by Inducing Oxidative Stress

Isoalantolactone Increases the Sensitivity of Prostate Cancer Cells to Cisplatin Treatment by Inducing Oxidative Stress

Feiyanning formula modulates the molecular mechanism of osimertinib resistance in lung cancer by regulating the Wnt/β-catenin pathway

NPCDR: natural product-based drug combination and its disease-specific molecular regulation

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