Chemotherapeutic Efficacy Enhancement in P-gp-Overexpressing Cancer Cells by Flavonoid-Loaded Polymeric Micelles

Khonkarn, Ruttiros; Daowtak, Krai; Okonogi, Siriporn

doi:10.1208/s12249-020-01657-5

Cited by 18 publications

(10 citation statements)

References 48 publications

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“…PI3K acts as an upstream mediator of P-gp in cancer cells, and reducing its expression is correlated with downregulation of P-gp and chemosensitivity [130]. Notably, phytochemicals are potential agents in suppressing P-gp expression and promoting DOX sensitivity [131]. The interesting point is that activity of P-gp can be affected by other proteins in cancer cells.…”

Section: Potential Mechanisms Of Dox Resistancementioning

confidence: 99%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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Doxorubicin (DOX) is a well-known chemotherapeutic agent extensively applied in the field of cancer therapy. However, similar to other chemotherapeutic agents such as cisplatin, paclitaxel, docetaxel, etoposide and oxaliplatin, cancer cells are able to obtain chemoresistance that limits DOX efficacy. In respect to dose-dependent side effect of DOX, enhancing its dosage is not recommended for effective cancer chemotherapy. Therefore, different strategies have been considered for reversing DOX resistance and diminishing its side effects. Phytochemical are potential candidates in this case due to their great pharmacological activities. Curcumin is a potential antitumor phytochemical isolated from Curcuma longa with capacity of suppressing cancer metastasis and proliferation and affecting molecular pathways. Experiments have demonstrated the potential of curcumin for inhibiting chemoresistance by downregulating oncogene pathways such as MMP-2, TGF-β, EMT, PI3K/Akt, NF-κB and AP-1. Furthermore, coadministration of curcumin and DOX potentiates apoptosis induction in cancer cells. In light of this, nanoplatforms have been employed for codelivery of curcumin and DOX. This results in promoting the bioavailability and internalization of the aforementioned active compounds in cancer cells and, consequently, enhancing their antitumor activity. Noteworthy, curcumin has been applied for reducing adverse effects of DOX on normal cells and tissues via reducing inflammation, oxidative stress and apoptosis. The current review highlights the anticancer mechanism, side effects and codelivery of curcumin and DOX via nanovehicles.

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Section: Potential Mechanisms Of Dox Resistancementioning

confidence: 99%

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

et al. 2020

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“…Khonkarn et al demonstrated that polymeric micelles of benzoylated methoxy-poly (ethylene glycol)-b-oligo(ε-caprolactone) or mPEG-b-OCL-Bz loaded with quercetin could represent an attractive tool to overcome MDR in cancer cells. Eventually, the combination of polymeric micelles (inhibiting P-gp efflux) and quercetin (interfering with the mitochondrial membrane potential) may represent crucial factors for the reversal of MDR in K562/ADR cells; quercetin also enhanced the cytotoxicity of doxorubicin and daunorubicin [ 116 ]. Also, the co-encapsulation of paclitaxel and naringin in mixed polymeric micelles improved the intracellular uptake and in vitro cytotoxicity of paclitaxel against breast cancer cells [ 117 ].…”

Section: Anti-cancer Chemotherapy Resistancementioning

confidence: 99%

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

et al. 2021

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Cost-efficacy of currently applied treatments is an issue in overall cancer management challenging healthcare and causing tremendous economic burden to societies around the world. Consequently, complex treatment models presenting concepts of predictive diagnostics followed by targeted prevention and treatments tailored to the personal patient profiles earn global appreciation as benefiting the patient, healthcare economy, and the society at large. In this context, application of flavonoids as a spectrum of compounds and their nano-technologically created derivatives is extensively under consideration, due to their multi-faceted anti-cancer effects applicable to the overall cost-effective cancer management, primary, secondary, and even tertiary prevention. This article analyzes most recently updated data focused on the potent capacity of flavonoids to promote anti-cancer therapeutic effects and interprets all the collected research achievements in the frame-work of predictive, preventive, and personalized (3P) medicine. Main pillars considered are:- Predictable anti-neoplastic, immune-modulating, drug-sensitizing effects;- Targeted molecular pathways to improve therapeutic outcomes by increasing sensitivity of cancer cells and reversing their resistance towards currently applied therapeutic modalities.

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“…According to the Western blot analysis, the co-treatment group (quercetin and cisplatin) showed lower levels of P-gp compared to the single-drug groups [107]. Moreover, other studies have shown a quercetin downregulation effect on P-gp efflux function [108,115,116]. Kaempferol is a natural flavonoid that was able to reverse the multidrug resistance in HepG2and N1S1 liver cancer cells via reducing P-gp overexpression [117].…”

Section: P-glycoproteinmentioning

confidence: 99%

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

et al. 2021

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Cancer is one of the leading causes of death globally. The development of drug resistance is the main contributor to cancer-related mortality. Cancer cells exploit multiple mechanisms to reduce the therapeutic effects of anticancer drugs, thereby causing chemotherapy failure. Natural products are accessible, inexpensive, and less toxic sources of chemotherapeutic agents. Additionally, they have multiple mechanisms of action to inhibit various targets involved in the development of drug resistance. In this review, we have summarized the basic research and clinical applications of natural products as possible inhibitors for drug resistance in cancer. The molecular targets and the mechanisms of action of each natural product are also explained. Diverse drug resistance biomarkers were sensitive to natural products. P-glycoprotein and breast cancer resistance protein can be targeted by a large number of natural products. On the other hand, protein kinase C and topoisomerases were less sensitive to most of the studied natural products. The studies discussed in this review will provide a solid ground for scientists to explore the possible use of natural products in combination anticancer therapies to overcome drug resistance by targeting multiple drug resistance mechanisms.

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Chemotherapeutic Efficacy Enhancement in P-gp-Overexpressing Cancer Cells by Flavonoid-Loaded Polymeric Micelles

Cited by 18 publications

References 48 publications

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Polychemotherapy with Curcumin and Doxorubicin via Biological Nanoplatforms: Enhancing Antitumor Activity

Flavonoids as an effective sensitizer for anti-cancer therapy: insights into multi-faceted mechanisms and applicability towards individualized patient profiles

Targeting Drug Chemo-Resistance in Cancer Using Natural Products

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