Apigenin in Combination with Akt Inhibition Significantly Enhances Thyrotropin-Stimulated Radioiodide Accumulation in Thyroid Cells

Lakshmanan, Aparna; Doseff, Andrea I.; Ringel, Matthew D.; Saji, Motoyasu; Rousset, Bernard; Zhang, Xiaoli; Jhiang, Sissy

doi:10.1089/thy.2013.0614

Cited by 15 publications

(14 citation statements)

References 42 publications

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“…Treatment with apigenin increases radioiodide accumulation in thyroid cells expressing BRAFV600E and in primary cultured thyroid tumor cells from TRβ (PV/PV) mice. Thus, along with Akt inhibitors, apigenin can further enhance the efficacy of radioiodine therapy for thyroid cancer patients [195]. Apigenin-induced cell death has been shown to involve autophagy in papillary thyroid cancer, perhaps because of ROS stimulation, induction of DNA damage and G2/M phase cell cycle arrest [196].…”

Section: 0 Effect Of Apigenin In Various Human Cancersmentioning

confidence: 99%

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: 0 Effect Of Apigenin In Various Human Cancersmentioning

confidence: 99%

Plant Flavone Apigenin: an Emerging Anticancer Agent

et al. 2017

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“…Treatment with apigenin at concentrations of 12.5∼100 μM can inhibit the proliferation of BCPAP cells arrested in the G2/M phase and induce autophagy via ROSmediated DNA damage [39]. Moreover, combining with apigenin and AKT inhibitors enhances the antitumor effects of radioiodine in both BRAF V600E -expressed rat thyroid cells and primary cultured PTC cells from TRβ PV/PV mice [40]. Unlike those of apigenin, the effects of quercetin on thyroid cells have been disputed.…”

Section: Flavonoidsmentioning

confidence: 99%

Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma

Yang

Chen

et al. 2020

BioMed Research International

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Papillary thyroid carcinoma (PTC) is the most common subtype of differentiated thyroid cancers in Asian coastal cities, where the patients have increased risk of potentially high or excessive iodine intake. Given the high metastasis and recurrence of patients with BRAFV600E mutation, the mortality rate of thyroid cancer has recently shown an upward trend. A variety of therapies, including surgery, radiotherapy, and chemotherapy, have been used to treat thyroid cancer, but these therapies still have limitations, including postoperative complications, drug resistance, poor efficacy, or serious side effects. Recent studies have shown the potential of active ingredients derived from herbal medicine in inhibiting PTC via various cell signaling pathways. Some plant-derived compounds, such as apigenin, genistein, and curcumin, are also known to prevent and treat PTC. This article summarizes the recent advances in the structure-functional impact of anti-PTC active ingredients and their effects on PTC cells and tumor microenvironments with an emphasis on their challenges from basic research to clinical practice.

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“…NIS protein level was decreased by 43 % upon 12-h treatment of TGF-β in PCCl3 thyroid cells under chronic TSH stimulation, where the half-life of NIS protein is 5 days in the absence of TGF-β (Lakshmanan and Jhiang, unpublished data). We reported that Akt inhibitor alone [33] or in combination with apigenin [45] increased iodide influx rate without increasing cell surface NIS protein levels.…”

Section: Modulation Of Nis-mediated Iodide Influx Iodide Efflux Andmentioning

confidence: 99%

“…Ser-43 was conserved in human NIS, and its phosphorylation is also critical for hNIS activity. Interestingly, we noted that NIS mobility was shifted upwards in SDS-denatured polyacryl-amide gel electrophoresis upon combination treatment of Akt inhibitor and apigenin in PCCl3 rat thyroid cells [45]. The nature of this mobility shift in NIS remains unclear and it may be due to a post-translational modification.…”

Section: Modulation Of Nis-mediated Iodide Influx Iodide Efflux Andmentioning

confidence: 99%

Modulation of Sodium Iodide Symporter in Thyroid Cancer

et al. 2014

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Radioactive iodine (RAI) is a key therapeutic modality for thyroid cancer. Loss of RAI uptake in thyroid cancer inversely correlates with patient’s survival. In this review, we focus on the challenges encountered in delivering sufficient doses of I-131 to eradicate metastatic lesions without increasing the risk of unwanted side effects. Sodium iodide symporter (NIS) mediates iodide influx, and NIS expression and function can be selectively enhanced in thyroid cells by thyroid-stimulating hormone. We summarize our current knowledge of NIS modulation in normal and cancer thyroid cells, and we propose that several reagents evaluated in clinical trials for other diseases can be used to restore or further increase RAI accumulation in thyroid cancer. Once validated in preclinical mouse models and clinical trials, these reagents, mostly small-molecule inhibitors, can be readily translated into clinical practice. We review available genetically engineered mouse models of thyroid cancer in terms of their tumor development and progression as well as their thyroid function. These mice will not only provide important insights into the mechanisms underlying the loss of RAI uptake in thyroid tumors but will also serve as preclinical animal models to evaluate the efficacy of candidate reagents to selectively increase RAI uptake in thyroid cancers. Taken together, we anticipate that the optimal use of RAI in the clinical management of thyroid cancer is yet to come in the near future.

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Apigenin in Combination with Akt Inhibition Significantly Enhances Thyrotropin-Stimulated Radioiodide Accumulation in Thyroid Cells

Abstract: Taken together, Apigenin may serve as a dietary supplement in combination with Akt inhibitors to enhance therapeutic efficacy of radioiodine for thyroid cancer.

Cited by 15 publications

References 42 publications

Plant Flavone Apigenin: an Emerging Anticancer Agent

Plant Flavone Apigenin: an Emerging Anticancer Agent

Herbal Active Ingredients: An Emerging Potential for the Prevention and Treatment of Papillary Thyroid Carcinoma

Modulation of Sodium Iodide Symporter in Thyroid Cancer

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