Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway

Gao, Ai-Mei; Ke, Zun‐Ping; Wang, Jia‐Ning; Yang, Jian-Ye; Chen, Shiyou; Chen, Hui

doi:10.1093/carcin/bgt108

Cited by 155 publications

(109 citation statements)

References 24 publications

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“…Apigenin and ADM co-treatment resulted in reduced proliferation, tumor growth inhibition, and apoptosis induction, compared to ADM treatment alone. These results underline the role of apigenin as an adjuvant to overcome chemoresistance [95]. In hepatocellular carcinoma tumors, apigenin enhanced the cytotoxicity of fluorouracil (5-FU), overcoming resistance by inhibiting ROS-mediated drug resistance, leading to mitochondrial depolarization and apoptosis [96].…”

Section: Effect Of Apigenin In Various Human Cancersmentioning

confidence: 98%

“…Furthermore, in vivo , combined treatment with 20 mg/kg apigenin five times per week in 3 week protocol and 20 mg/kg 5-FU for 5 consecutive days significantly inhibited the growth of HCC xenograft tumors [222]. Gao et al [95] demonstrated that apigenin significantly sensitizes doxorubicin-resistant BEL-7402 (BEL-7402/ADM) cells to doxorubicin (ADM) and increases intracellular concentration of ADM through downregulation of PI3K/Akt pathway, leading to a reduction of Nrf2-downstream genes. In BEL-7402 xenografts, apigenin and ADM cotreatment inhibited tumor growth, reduced cell proliferation and induced apoptosis more substantially when compared with ADM treatment alone.…”

Section: Combinational Studies With Apigeninmentioning

confidence: 99%

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Plant Flavone Apigenin: an Emerging Anticancer Agent

et al. 2017

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Research in cancer chemoprevention provides convincing evidence that increased intake of vegetables and fruits may reduce the risk of several human malignancies. Phytochemicals present therein provide beneficial anti-inflammatory and antioxidant properties that serve to improve the cellular microenvironment. Compounds known as flavonoids categorized anthocyanidins, flavonols, flavanones, flavonols, flavones, and isoflavones have shown considerable promise as chemopreventive agents. Apigenin (4′, 5, 7-trihydroxyflavone), a major plant flavone, possessing antioxidant, anti-inflammatory, and anticancer properties affecting several molecular and cellular targets used to treat various human diseases. Epidemiologic and case-control studies have suggested apigenin reduces the risk of certain cancers. Studies demonstrate that apigenin retain potent therapeutic properties alone and/or increases the efficacy of several chemotherapeutic drugs in combination on a variety of human cancers. Apigenin’s anticancer effects could also be due to its differential effects in causing minimal toxicity to normal cells with delayed plasma clearance and slow decomposition in liver increasing the systemic bioavailability in pharmacokinetic studies. Here we discuss the anticancer role of apigenin highlighting its potential activity as a chemopreventive and therapeutic agent. We also highlight the current caveats that preclude apigenin for its use in the human trials.

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Section: Effect Of Apigenin In Various Human Cancersmentioning

confidence: 98%

Section: Combinational Studies With Apigeninmentioning

confidence: 99%

Plant Flavone Apigenin: an Emerging Anticancer Agent

et al. 2017

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“…The NRF2 pathway has become a target for development of antineoplastic agents. Several natural compounds (trig-onelline, 101 apigenin, 102 and brusatol 103 ) reduce NRF2 activity through various mechanisms (Table 4). Preclinical studies of these inhibitors demonstrated their antitumor properties and synergistic effect with chemotherapeutic agents.…”

Section: Escc Signaling Pathways and Therapeutic Targetsmentioning

confidence: 99%

Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients

2018

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Esophageal squamous cell carcinoma (ESCC) is a common malignancy without effective therapy. The exomes of more than 600 ESCCs have been sequenced in the past 4 years, and numerous key aberrations have been identified. Recently, researchers reported both inter- and intratumor heterogeneity. Although these are interesting observations, their clinical implications are unclear due to the limited number of samples profiled. Epigenomic alterations, such as changes in DNA methylation, histone acetylation, and RNA editing, also have been observed in ESCCs. However, it is not clear what proportion of ESCC cells carry these epigenomic aberrations or how they contribute to tumor development. We review the genomic and epigenomic characteristics of ESCCs, with a focus on emerging themes. We discuss their clinical implications and future research directions.

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“…As a result, tumor cell apoptosis induced by oxaliplatin, bleomycin and DOX in lung cancer cells treated with luteolin is increased. Other similar flavonoids include chrysin (Gao et al, 2013a), apigenin (Gao et al, 2013b), Wogonin (Xu et al, 2014) and 3 0 , 4 0 , 5 0 , 5, 7-pentamethoxyflavone (PMF) . Interestingly, flavonoids are well known as antioxidative and cytoprotective chemicals, and their NRF2-inducible effect has been observed in some researches (Hanneken et al, 2006;Lemmens et al, 2014;Leonardo & Dore, 2011).…”

Section: Exogenous Natural Inhibitorsmentioning

confidence: 99%

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

Bai

Chen

Hou

et al. 2016

Drug Metabolism Reviews

137

105

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Chemoresistance is a disturbing barrier in cancer therapy, which always results in limited therapeutic options and unfavorable prognosis. Nuclear factor E2-related factor 2 (NRF2) controls the expression of genes encoding cytoprotective enzymes and transporters that protect against oxidative stress and electrophilic injury to maintain intrinsic redox homeostasis. However, recent studies have demonstrated that aberrant activation of NRF2 due to genetic and/or epigenetic mutations in tumor contributes to the high expression of phase I and phase II drug-metabolizing enzymes, phase III transporters, and other cytoprotective proteins, which leads to the decreased therapeutic efficacy of anticancer drugs through biotransformation or extrusion during chemotherapy. Therefore, a better understanding of the role of NRF2 in regulation of these enzymes and transporters in tumors is necessary to find new strategies that improve chemotherapeutic efficacy. In this review, we summarized the recent findings about the chemoresistance-promoting role of NRF2, NRF2-regulated phase I and phase II drug-metabolizing enzymes, phase III drug efflux transporters, and other cytoprotective genes. Most importantly, the potential of NRF2 was proposed to counteract drug resistance in cancer treatment.

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Apigenin sensitizes doxorubicin-resistant hepatocellular carcinoma BEL-7402/ADM cells to doxorubicin via inhibiting PI3K/Akt/Nrf2 pathway

Cited by 155 publications

References 24 publications

Plant Flavone Apigenin: an Emerging Anticancer Agent

Plant Flavone Apigenin: an Emerging Anticancer Agent

Genomic and Epigenomic Aberrations in Esophageal Squamous Cell Carcinoma and Implications for Patients

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters

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