Collateral sensitivity of natural products in drug-resistant cancer cells

Efferth, Thomas; Saeed, Mohamed E.M.; Kadioglu, Onat; Seo, Ean‐Jeong; Shirooie, Samira; Mbaveng, Armelle T.; Nabavi, Seyed Mohammad; Kuete, Victor

doi:10.1016/j.biotechadv.2019.01.009

Cited by 97 publications

(51 citation statements)

References 136 publications

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“…In recent years, natural compounds have become a hot research topic in preventing and treating cancer, due to their potential multiple targets and bioactivities and their limited toxicity (Efferth et al, 2019). Eriodictyol ( Figure 1A), a natural flavonoid compound, is ubiquitous in fruits, vegetables, and several Chinese medicines (Minato et al, 2003;Zeng et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Eriodictyol Inhibits Proliferation, Metastasis and Induces Apoptosis of Glioma Cells via PI3K/Akt/NF-κB Signaling Pathway

et al. 2020

Front. Pharmacol.

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Glioma is the most common type of malignant brain tumor. Due to its highly aggressive and metastatic features, glioma is associated with poor prognosis and a lack of effective treatments. Eriodictyol, a natural flavonoid compound, has been reported to possess antiinflammatory and antioxidant effects. However, the anti-tumor effects of eriodictyol and the underlying mechanisms have rarely been reported. In this study, we found that eriodictyol has anti-tumor activity in lung, colon, breast, pancreas, and liver cancer, and most significantly in glioma cell lines. Eriodictyol dose-and time-dependently suppresses cell proliferation, migration, and invasion in U87MG and CHG-5 glioma cells. In addition, eriodictyol induces apoptosis in U87MG and CHG-5 cells, as evaluated by flow cytometry, immunofluorescence, and Western blot. Furthermore, eriodictyol downregulates the phosphoinositide 3-kinase (PI3K)/Akt/NF-kB signaling pathway in a concentrationdependent manner. Moreover, the effects of eriodictyol on the apoptosis of glioma cells are enhanced by LY294002 (a PI3K inhibitor) and reversed by 740 Y-P (a PI3K agonist). In a mouse xenograft model, eriodictyol not only dramatically suppressed tumor growth but also induced apoptosis in tumor cells. In summary, our data illustrate that eriodictyol effectively inhibits proliferation and metastasis and induces apoptosis of glioma cell lines, which might be a result of the blockade of the PI3K/Akt/NF-kB signaling pathway.

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Section: Introductionmentioning

confidence: 99%

Eriodictyol Inhibits Proliferation, Metastasis and Induces Apoptosis of Glioma Cells via PI3K/Akt/NF-κB Signaling Pathway

et al. 2020

Front. Pharmacol.

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“…However, the clinical relevance of such inhibitors remains questionable despite the existence of compounds with potent in vitro activity [2]. Alternatively, recent reports revealed several compounds selectively killing cells overexpressing ATPase efflux pumps, such as P-glycoprotein (P-gp/MDR1) and Multidrug resistance associated protein 1 (MRP1/ABC1) [5][6][7][8][9][10]. These molecules were shown to target MDR cancer cells, offering an emerging strategy for anticancer agent development [11,12].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Anticancer Cytotoxicity of Azaaurones Overcoming Multidrug Resistance

et al. 2020

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The resistance of tumors against anticancer drugs is a major impediment for chemotherapy. Tumors often develop multidrug resistance as a result of the cellular efflux of chemotherapeutic agents by ABC transporters such as P-glycoprotein (ABCB1/P-gp), Multidrug Resistance Protein 1 (ABCC1/MRP1), or Breast Cancer Resistance Protein (ABCG2/BCRP). By screening a chemolibrary comprising 140 compounds, we identified a set of naturally occurring aurones inducing higher cytotoxicity against P-gp-overexpressing multidrug-resistant (MDR) cells versus sensitive (parental, non-P-gp-overexpressing) cells. Follow-up studies conducted with the P-gp inhibitor tariquidar indicated that the MDR-selective toxicity of azaaurones is not mediated by P-gp. Azaaurone analogs possessing pronounced effects were then designed and synthesized. The knowledge gained from structure-activity relationships will pave the way for the design of a new class of anticancer drugs selectively targeting multidrug-resistant cancer cells.

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“…To combat drug resistance, there are two main strategies: (1) Drugs with novel modes of action to bypass resistance to established drugs or (2) inhibitors of resistance mechanisms for resensitization of tumor cells [ 8 ]. The most general approach has been the development of P-glycoprotein (P-gp) inhibitors to co-administer with anticancer drugs [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…The most general approach has been the development of P-glycoprotein (P-gp) inhibitors to co-administer with anticancer drugs [ 6 ]. This consists of the pharmacological blockage of drug transporters such as P-gp (a type of ABC transporter) [ 8 ], that can lower intracellular drug concentration by expelling the drug from cancer cells [ 5 ]. However, despite their great in vitro success, there is no P-gp inhibitor currently available for clinical use [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Zoopharmacology: A Way to Discover New Cancer Treatments

et al. 2020

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Zoopharmacognosy is the multidisciplinary approach of the self-medication behavior of many kinds of animals. Recent studies showed the presence of antitumoral secondary metabolites in some of the plants employed by animals and their use for the same therapeutic purposes in humans. Other related and sometimes confused term is Zootherapy, which consists on the employment of animal parts and/or their by-products such as toxins, venoms, etc., to treat different human ailments. Therefore, the aim of this work is to provide a brief insight for the use of Zoopharmacology (comprising Zoopharmacognosy and Zootherapy) as new paths to discover drugs studying animal behavior and/or using compounds derived from animals. This work is focused on the approaches related to cancer, in order to propose a new promising line of research to overcome multidrug resistance (MDR). This novel subject will encourage the use of new alternative prospective ways to find new medicines.

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Collateral sensitivity of natural products in drug-resistant cancer cells

Cited by 97 publications

References 136 publications

Eriodictyol Inhibits Proliferation, Metastasis and Induces Apoptosis of Glioma Cells via PI3K/Akt/NF-κB Signaling Pathway

Eriodictyol Inhibits Proliferation, Metastasis and Induces Apoptosis of Glioma Cells via PI3K/Akt/NF-κB Signaling Pathway

Synthesis and Anticancer Cytotoxicity of Azaaurones Overcoming Multidrug Resistance

Zoopharmacology: A Way to Discover New Cancer Treatments

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