Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest

Ujiki, Michael; Ding, Xian; Salabat, Mohammad R.; Bentrem, David J.; Golkar, Laleh; Milam, Ben; Talamonti, Mark S.; Bell, Richard H.; Iwamura, Takeshi; Adrian, Thomas E.

doi:10.1186/1476-4598-5-76

Cited by 166 publications

(82 citation statements)

References 35 publications

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“…Studies with apigenin in combination with cell cycle inhibitor flavopiridol have shown to inhibit pancreatic tumor growth through suppression of cyclin B-associated cdc2 activity and G2/M arrest [110]. Apigenin administered in combination with gemcitabine enhanced anti-tumor efficacy through suppression of Akt and NF-κB activity and apoptosis induction in human pancreatic cancer MiaPaca-2 and AsPC-1 cells and pancreatic tumors from nude mice [111].…”

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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“…In epidermal cells and fibroblasts reversible G2/M and G0/G1 arrest is also mediated by the inhibition of p34 (Cdc2) kinase activity [78,79], while in breast carcinoma the G2/M phase cell cycle arrest after apigenin treatment led to a significant decrease in cyclins (B1, D1, and A) and cyclin-dependent kinase (Cdk1 and 4) protein levels [80]. In pancreatic cancer cell lines, apigenin caused both time- and concentration-dependent inhibition of DNA synthesis and cell proliferation through G2/M phase cell cycle arrest caused by the suppression of cyclin B-associated Cdc2 activity [81,82]. Moreover, in the same cell lines, it inhibited the glycogen synthase kinase-3β/NF-ĸB signaling pathway and upregulated the expression of cytokine genes, which potentially contributed to its anti-cancer properties [83].…”

Section: Preclinical Studiesmentioning

confidence: 99%

Chemopreventive Agents and Inhibitors of Cancer Hallmarks: May Citrus Offer New Perspectives?

et al. 2016

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Fruits and vegetables have long been recognized as potentially important in the prevention of cancer risk. Thus, scientific interest in nutrition and cancer has grown over time, as shown by increasing number of experimental studies about the relationship between diet and cancer development. This review attempts to provide an insight into the anti-cancer effects of Citrus fruits, with a focus on their bioactive compounds, elucidating the main cellular and molecular mechanisms through which they may protect against cancer. Scientific literature was selected for this review with the aim of collecting the relevant experimental evidence for the anti-cancer effects of Citrus fruits and their flavonoids. The findings discussed in this review strongly support their potential as anti-cancer agents, and may represent a scientific basis to develop nutraceuticals, food supplements, or complementary and alternative drugs in a context of a multi-target pharmacological strategy in the oncology.

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“…Apigenin is inexpensive to administer and is non-toxic at pharmacologic doses making it possible to administer concurrently with other chemotherapeutics whilst avoiding additive toxicity. [2] Apigenin has been shown to inhibit pancreatic cancer cell growth in vitro by induction of cell cycle arrest[3] and leads to synergistic effects when combined with gemcitabine by inhibiting pro-survival pathways involving pAKT which can contribute to gemcitabine resistance. [4] Breast and colon cancer cells respond similarly to apigenin treatment with cell cycle arrest and apoptosis induction which is linked to increased phosphorylation of p53 in both wild type and mutant p53-expressing cell lines.…”

Section: Introductionmentioning

confidence: 99%

Evidence for activation of mutated p53 by apigenin in human pancreatic cancer

King

et al. 2012

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Pancreatic cancer is an exceedingly lethal disease with a five-year survival that ranks among the lowest of gastrointestinal malignancies. Part of its lethality is attributable to a generally poor response to existing chemotherapeutic regimens. New therapeutic approaches are urgently needed. We aimed to elucidate the anti-neoplastic mechanisms of apigenin-an abundant, naturally-occurring plant flavonoid-with a particular focus on p53 function. Pancreatic cancer cells (BxPC-3, MiaPaCa-2) experienced dose and time-dependent growth inhibition and increased apoptosis with apigenin treatment. p53 post-translational modification, nuclear translocation, DNA binding, and upregulation of p21 and PUMA were all enhanced by apigenin treatment despite mutated p53 in both cell lines. Transcription-dependent p53 activity was reversed by pifithrin-α, a specific DNA binding inhibitor of p53, but not growth inhibition or apoptosis suggesting transcription-independent p53 activity. This was supported by immunoprecipitation assays which demonstrated disassociation of p53/BclXL and PUMA/BclXL and formation of complexes with Bak followed by Cytochrome c release. Treated animals grew smaller tumors with increased cellular apoptosis than those fed control diet. These results suggest that despite deactivating mutation, p53 retains some of its function which is augmented following treatment with apigenin. Cell cycle arrest and apoptosis induction may be mediated by transcription-independent p53 function via interactions with BclXL and PUMA. Further study of flavonoids as chemotherapeutics is warranted

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Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest

Cited by 166 publications

References 35 publications

Plant Flavone Apigenin: an Emerging Anticancer Agent

Plant Flavone Apigenin: an Emerging Anticancer Agent

Chemopreventive Agents and Inhibitors of Cancer Hallmarks: May Citrus Offer New Perspectives?

Evidence for activation of mutated p53 by apigenin in human pancreatic cancer

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