Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein

Zhang, Fa Yun; Du, Gang; Zhang, Ling; Zhang, Chun Ling; Lu, Wan Liang; Liang, Wei

doi:10.1007/s11095-008-9793-y

Cited by 78 publications

(36 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nar potentiates the chemosensitivity of tested cancer cells in a drug- and cancer-type dependent manner (Figures 6, 7, Table 2). These results are in line with findings in other malignancies [31,72,73]. …”

Section: Discussionsupporting

confidence: 93%

Growth inhibitory and chemo-sensitization effects of naringenin, a natural flavanone purified from Thymus vulgaris, on human breast and colorectal cancer

et al. 2015

View full text Add to dashboard Cite

BackgroundNatural products with diverse bioactivities are becoming an important source of novel agents with medicinal potential. Cancer is a devastating disease that causes the death of millions of people each year. Thus, intense research has been conducted on several natural products to develop novel anticancer drugs.MethodsChromatographic and spectral techniques were used for the isolation and identification of naringenin (Nar). MTT, flow cytometry, western blotting, Real Time PCR were used to test anticancer and chemosensitizing effects of Nar, cell cycle, apoptosis, and expression of cell cycle, apoptosis, pro-survival and anti-survival-related genes.ResultsIn the present study, Thymus vulgaris ethanol extract was purified repeatedly to produce several compounds including the known flavanone, Nar which was identified using different spectral techniques. Nar was shown to inhibit both human colorectal and breast cancer cell growth in a dose- and time-dependent manner through cell cycle arrest at S- and G2/M-phases accompanied by an increase in apoptotic cell death. Additionally, Nar altered the expression of apoptosis and cell-cycle regulatory genes by down-regulating Cdk4, Cdk6, Cdk7, Bcl2, x-IAP and c-IAP-2 and up-regulating p18, p19, p21, caspases 3, 7, 8 and 9, Bak, AIF and Bax in both colorectal and breast cancer cells. Conversely, it diminished the expression levels of the cell survival factors PI3K, pAkt, pIκBα and NFκBp65. Moreover, Nar enhanced the sensitivity of colorectal and breast cancer cells to DNA-acting drugs.DiscussionThese findings provide evidence that Nar’s pro-apoptotic and chemo-sensitizing effects are mediated by perturbation of cell cycle, upregulation of pro-apoptotic genes and down-regulation of anti-apoptotic genes and inhibition of pro-survival signaling pathways.ConclusionIn conclusion, Nar might be a promising candidate for chemoprevention and/or chemotherapy of human cancers. However, further studies exploring this therapeutic strategy are necessary.

show abstract

Section: Discussionsupporting

confidence: 93%

Growth inhibitory and chemo-sensitization effects of naringenin, a natural flavanone purified from Thymus vulgaris, on human breast and colorectal cancer

et al. 2015

View full text Add to dashboard Cite

show abstract

“…30 Naringenin, which is the aglycone of naringin, has been proven to enhance the antitumor effect of doxorubicin by inhibition of multidrug resistance associated proteins. 31 Naringenin inhibitscatenin/Tcf signaling in gastric cancer although the mechanisms remain unknown. 32 The citrus flavonoids hesperetin differentially regulate low density lipoprotein receptor gene transcription in HepG2 liver cells.…”

Section: Discussionmentioning

confidence: 99%

Antitumor potential of Citrus limetta fruit peel in Ehrlich ascites carcinoma bearing Swiss albino mice

et al. 2012

View full text Add to dashboard Cite

Citrus limetta Risso (Rutaceae), commonly known as sweet lime in English and Mousambi in India, has been traditionally used for several medicinal purposes. This study explored the relationship between Citrus limetta fruit peel and its antitumor activity against Ehrlich ascites carcinoma (EAC) bearing mice. The antitumor activity of methanol extract of peel of Citrus limetta fruits (MECL) was evaluated against EAC cell line in Swiss albino mice. Twenty-four hours after intraperitoneal inoculation of tumor EAC cells in mice, MECL was administered at 200 and 400 mg/kg body weight i.p. daily for nine consecutive days. On the 10 th day, half of the mice were sacrificed for the estimation of tumor growth (tumor volume, viable and non-viable tumor cell counts), and hematologic parameters (red blood cells, white blood cells and hemoglobin). The rest were kept alive for assessment of survival parameters, i.e. median survival time and percentage increase in life span of EAC bearing mice. Intraperitoneal administration of MECL at the doses of 200 and 400 mg/kg for nine days to the carcinoma induced mice demonstrated a significant (P<0.001) decrease in tumor volume, viable tumor cell count, tumor weight and a significant (P<0.001) improvement in hematologica parameters and life span as compared to the EAC control mice. The present study establishes marked and dose dependant antitumor effect of C. limetta fruit peel against Ehrlich ascites carcinoma bearing Swiss mice.

show abstract

“…The viabilities of treated and untreated cells were determined by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay which measures the mitochondrial conversion of MTT to formazan as detected by the change of optical density at 570 nm [16], [17]. Briefly, MCF-7 and U-118MG cells were plated at a density of 4×10 3 and 3×10 3 cells per well respectively in 100 µl DMEM medium in 96-well plates and allowed to grow for 24 hours.…”

Section: Methodsmentioning

confidence: 99%

Improved Efficacy and Reduced Toxicity of Doxorubicin Encapsulated in Sulfatide-Containing Nanoliposome in a Glioma Model

Shigdar

Fang

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

As a glycosphingolipid that can bind to several extracellular matrix proteins, sulfatide has the potential to become an effective targeting agent for tumors overexpressing tenasin-C in their microenvironment. To overcome the dose-limiting toxicity of doxorubicin (DOX), a sulfatide-containing nanoliposome (SCN) encapsulation approach was employed to improve treatment efficacy and reduce side effects of free DOX. This study analysed in vitro characteristics of sulfatide-containing nanoliposomal DOX (SCN-DOX) and assessed its cytotoxicity in vitro, as well as biodistribution, therapeutic efficacy, and systemic toxicity in a human glioblastoma U-118MG xenograft model. SCN-DOX was shown to achieve highest drug to lipid ratio (0.5∶1) and a remarkable in vitro stability. Moreover, DOX encapsulated in SCN was shown to be delivered into the nuclei and displayed prolonged retention over free DOX in U-118MG cells. This simple two-lipid SCN-DOX nanodrug has favourable pharmacokinetic attributes in terms of prolonged circulation time, reduced volume of distribution and enhanced bioavailability in healthy rats. As a result of the improved biodistribution, an enhanced treatment efficacy of SCN-DOX was found in glioma-bearing mice compared to the free drug. Finally, a reduction in the accumulation of DOX in the drug's principal toxicity organs achieved by SCN-DOX led to the diminished systemic toxicity as evident from the plasma biochemical analyses. Thus, SCN has the potential to be an effective and safer nano-carrier for targeted delivery of therapeutic agents to tumors with elevated expression of tenascin-C in their microenvironment.

show abstract

Naringenin Enhances the Anti-Tumor Effect of Doxorubicin Through Selectively Inhibiting the Activity of Multidrug Resistance-Associated Proteins but not P-glycoprotein

Abstract: Naringenin enhances antitumor effect of doxorubicin by selective modulating drug efflux pathways. Naringenin will be a useful adjunct to improve the effectiveness of chemotherapeutic agents in treatment of human cancers.

Cited by 78 publications

References 37 publications

Growth inhibitory and chemo-sensitization effects of naringenin, a natural flavanone purified from Thymus vulgaris, on human breast and colorectal cancer

Growth inhibitory and chemo-sensitization effects of naringenin, a natural flavanone purified from Thymus vulgaris, on human breast and colorectal cancer

Antitumor potential of Citrus limetta fruit peel in Ehrlich ascites carcinoma bearing Swiss albino mice

Improved Efficacy and Reduced Toxicity of Doxorubicin Encapsulated in Sulfatide-Containing Nanoliposome in a Glioma Model

Contact Info

Product

Resources

About