Combination Treatment with Luteolin and Quercetin Enhances Antiproliferative Effects in Nicotine-Treated MDA-MB-231 Cells by Down-regulating Nicotinic Acetylcholine Receptors

Shih, Yung Leun; Liu, Hui Ching; Chen, Ching Shyang; Hsu, Chia-Hsiang; Pan, Min‐Hsiung; Chang, Hui; Chang, Chin Sung; Chen, Feng Chia; Ho, Chi Tang; Yang, Yi-Yuan; Ho, Yuan Soon

doi:10.1021/jf9031684

Cited by 67 publications

(57 citation statements)

References 33 publications

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“…Chiang et al reported that luteolin significantly suppresses the growth of MCF-7 and MDA-MB-435 breast tumor in vitro (17). Shinh et al reported that luteolin significantly decreased MCF-7 and MDA-MB-231 breast tumor growth in vitro (18). We have shown that the viability of MCF-7 cells was inhibited by luteolin after 72 h of treatment in a time-dependent (P=0.02) and concentration-dependent manner (P=0.04).…”

Section: Discussionmentioning

confidence: 99%

Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells

Jeon

Suh

2012

Oncology Reports

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Abstract. Breast cancer is heterogeneous and often hormonedependent. There are many breast cancer treatment options, including endocrine therapy, chemotherapy, radiotherapy and targeted therapy. Unfortunately, not all patients respond to first-line treatments, and others will eventually relapse despite an initial response. Therapeutic options for these patients are limited. In the past decade, several studies have demonstrated the antitumor effect of celecoxib and luteolin in breast cancer as single treatment. The effect of combination treatment of celecoxib and luteolin in human breast cancer cells has not been well characterized. The present study examined the synergistic effect of celecoxib and luteolin on the human breast cancer cell lines MCF-7 and MDA-MB-231. We analyzed cell proliferation, cell death, apoptosis and changes in protein expression by performing cell survival assays, apoptosis assays and western blotting. The combination treatment significantly decreased cancer cell viability, and it had a greater efficiency in killing tumor cells after 72 h of treatment, compared to treatment with either agent alone or the control in a concentration-and time-dependent manner (P=0.01). The combination treatment demonstrated a greater than additive increase in breast cancer cell apoptosis (P=0.01). Decreased levels of Akt phosphorylation (pAkt) were noted after celecoxib and luteolin combination treatment. The combination of celecoxib and luteolin provided superior inhibition of breast cancer cell growth than either celecoxib or luteolin treatment alone. These results suggest that celecoxib and luteolin combination may be a new possible treatment option for breast cancer.

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Section: Discussionmentioning

confidence: 99%

Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells

Jeon

Suh

2012

Oncology Reports

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“…1) (4). These signaling pathways are closely correlated to the formation of several cancers; in particular, a7-nAChR is associated with lung (5), bladder (6), and colon cancers (7), and a9-nAChR is associated with breast cancer (8)(9)(10) (Fig. 1).…”

Section: Biological Functions Of Nicotinic Acetylcholine Receptorsmentioning

confidence: 96%

“…Furthermore, nicotine has been shown to induce activation of NF-kB through the MAP kinase p38 and PI3K/AKT signaling pathways, promoting the survival, proliferation, and angiogenesis of ECs (32). Another study showed that AKT survival signals play an important role in the nicotinemediated carcinogenic process in human breast cancer cells (10).…”

Section: Nachr-mediated Signaling Pathwaysmentioning

confidence: 99%

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Lee

2011

Clinical Cancer Research

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103

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The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and a-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that a9-nAChR is important for breast cancer formation, and in many in vivo studies, a9-nAChR-specific antagonists (e.g., a-ImI, a-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine-and estrogeninduced breast cancer cell proliferation through inhibition of the a9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation.

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“…Quercetin (Que), an nAChR antagonist, was found to inhibit the proliferation of human breast cancer cells through blockage of Nic receptors and nAChR subunit expression. 5 Que is a component of most edible fruits and vegetables, with the highest concentrations found in onions, apples, and red wine. 6,7 Although the anticancer mechanisms are not yet fully understood, current evidence demonstrates that Que is beneficial for improving breast cancer chemotherapy and is a potential chemopreventive agent.…”

Section: Introductionmentioning

confidence: 99%

“…6,7 Although the anticancer mechanisms are not yet fully understood, current evidence demonstrates that Que is beneficial for improving breast cancer chemotherapy and is a potential chemopreventive agent. 5 However, the poor water solubility of Que leads to its minimal absorption in the gastrointestinal tract, and its oral bioavailability (BA) is 17% in rats and only 1% in men. 8,9 Que was previously applied in early-stage clinical trials as an anticancer agent; however, it required the use of solvents such as dimethyl sulfoxide (DMSO) or ethanol.…”

Section: Introductionmentioning

confidence: 99%

Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study

Chen¹,

Chen²,

Su³

et al. 2016

IJN

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Quercetin (Que) is known to have biological benefits including an anticancer effect, but low water solubility limits its clinical application. The aim of this study was to develop a lecithin-based mixed polymeric micelle (LMPM) delivery system to improve the solubility and bioavailability of Que. The optimal Que-LMPM, composed of Que, lecithin, Pluronic ® P123, and 1,2-distearoyl- sn -glycero-3-phosphoethanolamine- N -methoxy[poly(ethylene glycol)-2000] in a proportion of 3:1:17.5:2.5 (w/w), was prepared by a thin-film method. The average size, polydispersion index, encapsulating efficiency, and drug loading of Que-LMPM were 61.60±5.02 nm, 0.589±0.198, 96.87%±9.04%, and 12.18%±1.11%, respectively. The solubility of Que in the Que-LMPM system increased to 5.81 mg/mL, compared to that of free Que in water of 0.17–7.7 μg/mL. The Que-LMPM system presented a sustained-release property in vitro. The in vitro cytotoxicity assay showed that the 50% inhibitory concentration values toward MCF-7 breast cancer cells for free Que, blank LMPMs, and Que-LMPMs were >200, >200, and 110 μM, respectively, indicating the nontoxicity of the LMPM carrier, but the LMPM formulation enhanced the cytotoxicity of Que against MCF-7 cells. A cellular uptake assay also confirmed the intake of Que-LMPM by MCF-7 cells. An in vivo pharmacokinetic study demonstrated that Que-LMPMs had higher area under the concentration–time curve and a longer half-life, leading to better bioavailability compared to a free Que injection. Due to their nanosize, core–shell structure, and solubilization potential, LMPMs were successfully developed as a drug delivery system for Que to improve its solubility and bioavailability.

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Combination Treatment with Luteolin and Quercetin Enhances Antiproliferative Effects in Nicotine-Treated MDA-MB-231 Cells by Down-regulating Nicotinic Acetylcholine Receptors

Cited by 67 publications

References 33 publications

Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells

Synergistic apoptotic effect of celecoxib and luteolin on breast cancer cells

Nicotinic Acetylcholine Receptor-Based Blockade: Applications of Molecular Targets for Cancer Therapy

Development and characterization of self-assembling lecithin-based mixed polymeric micelles containing quercetin in cancer treatment and an in vivo pharmacokinetic study

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