Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P-glycoprotein expression

Sun, Li; Chen, Weigang; Qu, Lili; Wu, Jie; Jin, Si

doi:10.3892/mmr.2013.1742

Cited by 70 publications

(37 citation statements)

References 36 publications

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“…Icaritin, an active ingredient isolated from the medical plant Herba Epimedium, reverses MDR of HepG2/ADR human hepatoma cells via downregulation of MDR1 and Pgp expression (103). Pien Tze Huang, a well-known traditional Chinese medical formula, has been used in China and Southeast Asia for centuries as a folk remedy for various types of cancer.…”

Section: Kim Et Al Reported That Resveratrol Enhanced Doxorubicinindmentioning

confidence: 99%

Natural Product Modulators to Overcome Multidrug Resistance In Cancer

Çört

Özben

2015

Nutrition and Cancer

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Multidrug resistance (MDR) is a condition that makes cells simultaneously unresponsive to different drugs, unrelated to their chemical structure and mechanism of action. MDR caused by the presence and overexpression of ABC transporters makes obstacles in cancer treatment and lower the effectiveness of chemotherapy. Natural products are investigated by many researchers as MDR modulators for their low toxicity and potent, selective behavior. When coadministered, MDR modulators compete with cytotoxic agents for binding to the active site of the membrane transporters and reduce drug efflux. Natural product-based drugs are important in struggling against drug resistance during cancer therapy. This review is focused on the potential mechanisms against drug resistance, the development of inhibitors for ABC drug transporters, natural product modulators, and nanoparticle drug delivery.

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Section: Kim Et Al Reported That Resveratrol Enhanced Doxorubicinindmentioning

confidence: 99%

Natural Product Modulators to Overcome Multidrug Resistance In Cancer

Çört

Özben

2015

Nutrition and Cancer

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“…In various present studies, icaritin induces cell apoptosis in many solid tumors [2–7, 10, 11] and myeloid original malignancies [8, 9]. To determine whether icaritin induces apoptosis in lymphoid malignant cells, Raji cells were treated with different concentrations of icaritin for 48 h and Annexin V-FITC and PI fluorescence assays were performed to evaluate necrotic cells as well as early stage and late stage apoptotic cells.…”

Section: Resultsmentioning

confidence: 98%

“…Icaritin is a hydrolytic product of icariin that is extracted from Epimedium brevicornum, which is a traditional Chinese medicine (TCM). Icaritin has showed significant antitumor activities with minor side effects in various neoplasms, such as inducing apoptosis in human endometrial cancer Hec1A cells [2], leading to cell growth inhibition, G1 arrest, and apoptosis of prostate cancer PC-3 cells [3], resulting in cell cycle arrest at the G2/M phase, apoptotic cell death [4] and enhancing radio sensitivity [5] in breast cancer cells, inhibiting growth [6], and reversing multidrug resistance [7] of hepatoma HepG2 cells. For hematopoietic neoplasms, Li and his team demonstrated the antitumor effect of icaritin in acute myeloid leukemia cells [8], and we reported that icaritin showed potent antileukemia activity on chronic myeloid leukemia in vitro and in vivo [9].…”

Section: Introductionmentioning

confidence: 99%

Cytotoxic Effect of Icaritin and Its Mechanisms in Inducing Apoptosis in Human Burkitt Lymphoma Cell Line

Yao

Liu

et al. 2014

BioMed Research International

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Icaritin (ICT), a hydrolytic product of icariin from Epimedium genus, exhibits antitumor activities in several human solid-tumor and myeloid leukemia cells with extensive influence on various cell signal molecules, such as MAPKs being involved in cell proliferation and Bcl-2 participating in cell apoptosis. However, the effect of icaritin on Burkitt Lymphoma has not been elucidated. In the present study, we first screened the potential effect of icaritin on Burkitt lymphoma Raji and P3HR-1 cell lines and found that icaritin showed cytotoxicity in both cell lines. We further found that icaritin could significantly inhibit Raji cells proliferation with S-phase arrest of cell cycle and induced cell apoptosis accompanied by activation of caspase-8 and caspase-9 and cleavage of PARP. We also observed that icaritin was able to decrease Bcl-2 levels, thus shifting the Bcl-2/Bax ratio, and it could obviously reduce c-Myc, a specific molecular target in Burkitt lymphoma. Our findings demonstrated that icaritin showed cytotoxicity, inhibited cell growth, caused S arrest, and induced apoptosis in Burkitt lymphoma cells and provided a rationale for the further evaluation of icaritin for Burkitt lymphoma therapy.

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“…Despite the growth inhibitory effects of the non-fractionated aqueous extract of EG demonstrated in the current study, the identity of the water-soluble bioactive agent(s) in this extract remain unclear. Methanolic extracts from EG containing icariin and icaritin have been demonstrated to effect multidrug resistance in HepG2/ADR cells (26). In contrast, the same methanol soluble bioactive agents induce growth promoting effects through the upregulation of epidermal growth factor receptor/mitogen-activated protein kinase signaling pathways in a model of HER-2 + breast cancer (27).…”

Section: Discussionmentioning

confidence: 99%

The nutritional herb Epimedium grandiflorum inhibits the growth in a model for the Luminal A molecular subtype of breast cancer

Telang¹,

Gou²,

Katdare

et al. 2017

Oncology Letters

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Abstract. The Luminal A subtype of breast cancer expresses the estrogen receptor (ER)-α and progesterone receptor (PR), but not the human epidermal growth factor receptor (HER)-2 oncogene. This subtype of breast cancer responds to endocrine therapy involving the use of selective estrogen receptor modulators and/or inhibitors of estrogen biosynthesis. However, these therapeutic agents are frequently associated with long-term systemic toxicity and acquired tumor resistance, emphasizing the need to identify non-toxic alternative treatments for chemo-endocrine therapy responsive breast cancer. The present study utilized the human mammary carcinoma-derived, ER + /PR + /HER-2 -MCF-7 cell line as a model of the Luminal A subtype of breast cancer to examine the growth inhibitory effect of the Chinese nutritional herb Epimedium grandiflorum (EG) and determine the mechanisms underlying this effect. MCF-7 cells maintained in a serum-depleted culture medium retained their ability to grow in response to 17β-estradiol (E 2 ). Treatment of the MCF-7 cells with EG resulted in dose-dependent inhibition of E 2 -promoted growth. Mechanistically, EG inhibited E 2 -promoted cell cycle progression through G 1 stage arrest and modulated the cellular metabolism of E 2 , increasing the formation of the anti-proliferative metabolites 2-hydroxyestrone and estriol. Long-term treatment of MCF-7 cells with EG inhibited E 2 -promoted anchorage independent growth, a surrogate in vitro biomarker of tumorigenesis. In conclusion, the results of the present study demonstrate the growth inhibitory effects of EG on MCF-7 cells and identified clinically relevant mechanistic leads for its anti-tumorigenic efficacy. IntroductionMetastatic breast cancer is one of the leading causes of breast-cancer associated mortality in the United States, and the American Cancer Society (Atlanta, GA, USA) projections for breast cancer incidence and mortality rates estimate 246,660 newly diagnosed cases of invasive breast cancer and 40,450 metastatic breast cancer-associated mortalities in women in 2017 (1). These figures emphasize the requirement for a more precise molecular classification of breast cancer for subtype-specific targeted therapy, in addition to the necessity to identify novel, non-toxic and efficacious modalities as alternatives for cancer prevention and therapy.The global gene expression profiling of breast cancer has led to the identification of molecularly distinct subtypes. Patients with the molecular subtype Luminal A express estrogen receptor-α (ER)-α and progesterone receptor (PR), and they lack the expression of human epidermal growth factor receptor-2 (HER-2). Patients with this subtype respond to endocrine-based targeted therapy, such as selective ER modulators and specific small molecule inhibitors of estrogen biosynthesis (2-4). However, long-term endocrine-based therapy has been associated with adverse systemic toxicity, acquired tumor resistance and the emergence of drug resistant cancer stem cells that compromise therapeutic efficacy and ...

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Icaritin reverses multidrug resistance of HepG2/ADR human hepatoma cells via downregulation of MDR1 and P-glycoprotein expression

Cited by 70 publications

References 36 publications

Natural Product Modulators to Overcome Multidrug Resistance In Cancer

Natural Product Modulators to Overcome Multidrug Resistance In Cancer

Cytotoxic Effect of Icaritin and Its Mechanisms in Inducing Apoptosis in Human Burkitt Lymphoma Cell Line

The nutritional herb Epimedium grandiflorum inhibits the growth in a model for the Luminal A molecular subtype of breast cancer

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