Dietary Garcinol Arrests Pancreatic Cancer in p53 and K-ras Conditional Mutant Mouse Model

Saadat, Nadia; Akhtar, Sarah; Goja, Arvind; Razalli, Nurul Huda; Geamanu, Andreea; David, Doina; Shen, Yimin; Gupta, Smiti

doi:10.1080/01635581.2018.1502327

Cited by 14 publications

(15 citation statements)

References 34 publications

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“…Also, nanoformulations of garcinol have been found to be a promising strategy to improve its bioavailability [32]. The efficacy of garcinol as a promising anticancer agent has been demonstrated in several investigations that used in vivo models representing various human cancers [12,17,24,27,29,32,33,34].…”

Section: Discussionmentioning

confidence: 99%

Garcinol Sensitizes NSCLC Cells to Standard Therapies by Regulating EMT-Modulating miRNAs

Farhan

Malik

Ullah

et al. 2019

IJMS

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Garcinol, a dietary factor obtained from Garcinia indica, modulates several key cellular signaling pathways as well as the expression of miRNAs. Acquired resistance to standard therapies, such as erlotinib and cisplatin, is a hallmark of non-small cell lung cancer (NSCLC) cells that often involves miRNA-regulated epithelial-to-mesenchymal transition (EMT). We used A549 cells that were exposed to transforming growth factor beta 1 (TGF-β1), resulting in A549M cells with mesenchymal and drug resistant phenotype, and report that garcinol sensitized resistant cells with mesenchymal phenotype to erlotinib as well as cisplatin with significant decrease in their IC50 values. It also potentiated the apoptosis-inducing activity of erlotinib in A549M and the endogenously mesenchymal H1299 NSCLC cells. Further, garcinol significantly upregulated several key EMT-regulating miRNAs, such as miR-200b, miR-205, miR-218, and let-7c. Antagonizing miRNAs, through anti-miRNA transfections, attenuated the EMT-modulating activity of garcinol, as determined by mRNA expression of EMT markers, E-cadherin, vimentin, and Zinc Finger E-Box Binding Homeobox 1 (ZEB1). This further led to repression of erlotinib as well as cisplatin sensitization, thus establishing the mechanistic role of miRNAs, particularly miR-200c and let-7c, in garcinol-mediated reversal of EMT and the resulting sensitization of NSCLC cells to standard therapies.

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Section: Discussionmentioning

confidence: 99%

Garcinol Sensitizes NSCLC Cells to Standard Therapies by Regulating EMT-Modulating miRNAs

Farhan

Malik

Ullah

et al. 2019

IJMS

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“…In view of the present data, it is tempting to speculate that garcinol and related substances may be employed for the inhibition of platelet activation in the prophylaxis and/or treatment of thrombosis. Garcinol is a food additive which could be administrated to patients [40]. It must be kept in mind, though, that the present in-vitro studies in murine platelets cannot be translated without reservations into in-vivo effects on functions of human platelets.…”

Section: Discussionmentioning

confidence: 99%

Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis

Cao

Bhuyan

Umbach

et al. 2019

Toxins

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Garcinol, an anti-inflammatory and anti-carcinogenic polyisoprenylated benzophenone isolated from Garcinia plants, stimulates tumor cell apoptosis and suicidal erythrocyte death, but supports the survival of hepatocytes and neurons. The present study explored whether the substance influences platelet function and/or apoptosis. To this end, we exposed murine blood platelets to garcinol (33 µM, 30 min) without and with activation by collagen-related peptide (CRP) (2–5 µg/mL) or thrombin (0.01 U/mL); flow cytometry was employed to estimate cytosolic Ca2+-activity ([Ca2+]i) from Fluo-3 fluorescence, platelet degranulation from P-selectin abundance, integrin activation from αIIbβ3 integrin abundance, caspase activity utilizing an Active Caspase-3 Staining kit, phosphatidylserine abundance from annexin-V-binding, relative platelet volume from forward scatter, and aggregation utilizing staining with CD9-APC and CD9-PE. As a result, in the absence of CRP and thrombin, the exposure of the platelets to garcinol did not significantly modify [Ca2+]i, P-selectin abundance, activated αIIbβ3 integrin, annexin-V-binding, cell volume, caspase activity, and aggregation. Exposure of platelets to CRP or thrombin was followed by a significant increase of [Ca2+]i, P-selectin abundance, αIIbβ3 integrin activity, annexin-V-binding, caspase activity, and aggregation, as well as significant cell shrinkage. All effects of CRP were strong and significant; those of thrombin were only partially and slightly blunted in the presence of garcinol. In conclusion, garcinol blunts CRP-induced platelet activity, apoptosis and aggregation.

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“…In addition, upregulation of the tumor suppressor microRNA miR‐200c (target: Notch‐1) was observed upon garcinol treatment . In transgenic PC mice (KPC mice: K‐ras and p53 conditional mutant mice), garcinol and the combination of a garcinol diet with injected gemcitabine inhibited tumor growth …”

Section: An Update On the Activities Of Garcinol And Isogarcinol Agaimentioning

confidence: 99%

“…Increased apoptosis, inhibition of autophagy (garcinol) [38] Induction of Bax, suppression of Bcl-2 and mTOR (garcinol) [38] Inhibition of PC-3 mouse xenograft tumor growth (garcinol) [38] Pancreatic cancer Suppression of cancer stem cell character (garcinol), [40] tumor growth inhibition (garcinol) [41] Suppression of Mcl-1, EZH2, ABCG2, Gli-1, and Notch-1, induction of miR-200c (garcinol) [40] Inhibition of tumor growth in KPC mice: K-ras and p53 conditional mutant mice (garcinol) [41] Oral squamous cell carcinoma Inhibition of tumor cell growth, induction of apoptosis, inhibition of angiogenesis and colony formation (garcinol) [43] Inhibition of NF-κB and COX-2, suppression of VEGF (garcinol) [43] -Cervical cancer Inhibition of tumor cell growth (garcinol), [48,53] suppression of tumorigenesis (garcinol), [48] sensitization to radiotherapy (garcinol) [49] Activation of PI3 K/AKT signaling (garcinol), [48] suppression of HIF-1α (garcinol) [49] Induction of T-cadherin in vivo (garcinol) [48]…”

Section: Cancer Type Effects Mechanismsmentioning

confidence: 99%

“…[40] In transgenic PC mice (KPC mice: K-ras and p53 conditional mutant mice), garcinol and the combination of a garcinol diet with injected gemcitabine inhibited tumor growth. [41] With more than 300,000 people suffering from oral squamous cell carcinoma (OSCC) every year all over the world, this malignancy is the sixth most common tumor disease and many cases go on developing countries. [42] Garcinol inhibited the tumor cell growth of the OSCC cell lines SCC-4, SCC-9 and SCC-25 in vitro (IC 50 = 5À 15 μM), induced apoptosis in these cancer cells, blocked angiogenesis and reduced significantly the number of formed colonies by SCC-4 and SCC-9 cells.…”

Section: Miscellaneous Cancersmentioning

confidence: 99%

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Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

Schobert

Biersack

2019

Chemistry & Biodiversity

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The natural polyisoprenylated benzophenone derivatives garcinol and isogarcinol are secondary plant metabolites isolated from various Garcinia species including Garcinia indica. This review takes stock of the recent chemical and biological research into these interesting natural compounds over the last five years. New biological sources and chemical syntheses are discussed followed by new insights into the activity of garcinol and isogarcinol against cancer, pathogenic bacteria, parasite infections and various inflammatory diseases.

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Dietary Garcinol Arrests Pancreatic Cancer in p53 and K-ras Conditional Mutant Mouse Model

Cited by 14 publications

References 34 publications

Garcinol Sensitizes NSCLC Cells to Standard Therapies by Regulating EMT-Modulating miRNAs

Garcinol Sensitizes NSCLC Cells to Standard Therapies by Regulating EMT-Modulating miRNAs

Garcinol A Novel Inhibitor of Platelet Activation and Apoptosis

Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

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