Comparison of the effects of curcumin and curcumin glucuronide in human hepatocellular carcinoma HepG2 cells

Shoji, Motomu; Nakagawa, Kiyotaka; Watanabe, Akio; Tsuduki, Tsuyoshi; Yamada, Teiko; Kuwahara, Shigefumi; Kimura, Fumiko; Miyazawa, Teruo

doi:10.1016/j.foodchem.2013.11.021

Cited by 79 publications

(62 citation statements)

References 16 publications

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“…Curcumin (1, 7-bis-(4-hydroxy-3-methoxyphenyl)-1, 6-heptadiene-3, 5-dione), derived from the rhizome of the plant Curcuma longa L, has been used for thousands of years in Asia countries as a food additive, cosmetic, and as a traditional herbal medicine (Jiang et al, 2014;Shoji et al, 2014 shown that curcumin possessed the anticarcinogenic properties by modulating various mechanisms linked with the development and progression of cancer (Hasan et al, 2014). Apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies (Wong, 2011;Li et al, 2013;Singh et al, 2013;Gopal et al, 2014;.…”

Section: Introductionmentioning

confidence: 99%

Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways

Xue¹,

Yu²,

Sun³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7-AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.

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Section: Introductionmentioning

confidence: 99%

Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways

Xue¹,

Yu²,

Sun³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…[4][5][6] CUR's low bioavailability in vivo was confirmed by our previous work in which CUR absorbed through the intestinal cells of rats was predominantly conjugated as curcumin glucuronide (CURG) and low levels of unmetabolized CUR were found in the blood. 7,8 We hypothesized that encapsulating CUR with poly-(lactic-co-glycolic acid) (PLGA)-based nanoparticles would enhance the bioavailability of CUR administered orally because of PLGA's ability to disperse in water, pass through the gut, bypass first-pass metabolism, and endure the harsh external conditions of the gastrointestinal tract (chemical and enzymatic degradation). 4,[9][10][11][12][13] Our hypothesis is supported by previous studies that reported that encapsulated CUR with PLGA-based nanoparticles administrated orally to rats increased CUR levels in the plasma.…”

mentioning

confidence: 99%

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

Harigae¹,

Nakagawa²,

Miyazawa³

et al. 2016

IJN

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Purpose Curcumin (CUR), the main polyphenol in turmeric, is poorly absorbed and rapidly metabolized following oral administration, which severely curtails its bioavailability. Poly-(lactic-co-glycolic acid)-based CUR nanoparticles (CUR-NP) have recently been suggested to improve CUR bioavailability, but this has not been fully verified. Specifically, no data are available about curcumin glucuronide (CURG), the major metabolite of CUR found in the plasma following oral administration of CUR-NP. Herein, we investigated the absorption and metabolism of CUR-NP and evaluated whether CUR-NP improves CUR bioavailability. Methods Following oral administration of CUR-NP in rats, we analyzed the plasma and organ distribution of CUR and its metabolites using high-performance liquid chromatography-tandem mass spectrometry. To elucidate the mechanism of increased intestinal absorption of CUR-NP, we prepared mixed micelles comprised of phosphatidylcholine and bile salts and examined the micellar solubility of CUR-NP. Additionally, we investigated the cellular incorporation of the resultant micelles into differentiated Caco-2 human intestinal cells. Results Following in vivo administration of CUR-NP, CUR was effectively absorbed and present mainly as CURG in the plasma which contained significant amounts of the metabolite compared with other organs. Thus, CUR-NP increased intestinal absorption of CUR rather than decreasing metabolic degradation and conversion to other metabolites. In vitro, CUR encapsulated in CUR-NP was solubilized in mixed micelles; however, whether the micelles contained CUR or CUR-NP had little influence on cellular uptake efficiency. Therefore, we suggest that the high solubilization capacity of CUR-NP in mixed micelles, rather than cellular uptake efficiency, explains the high intestinal absorption of CUR-NP in vivo. Conclusion These findings provide a better understanding of the bioavailability of CUR and CUR-NP following oral administration. To improve the bioavailability of CUR, future studies should focus on enhancing the resistance to metabolic degradation and conversion of CUR to other metabolites, which may lead to novel discoveries regarding food function and disease prevention.

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“…[40] Unfortunately, curcumin has poor pharmacokinetics as it undergoes poor absorption and has low bioavailability. [43] Curcumin gets directly conjugated once it is absorbed, and only a small amount remains as free curcumin. [43] It has been suggested that its metabolite, curcumin glucuronide, is responsible for most of its therapeutically assumed action, [44] however, a recent study showed that curcumin glucuronide has a less potent effect than curcumin itself on HepG2 cells, as the expression of GSTT1, CAT, IL-8, AREG, and ACOX1 genes was greatly downregulated by curcumin than by curcumin glucuronide.…”

Section: Curcuminmentioning

confidence: 99%

“…[43] It has been suggested that its metabolite, curcumin glucuronide, is responsible for most of its therapeutically assumed action, [44] however, a recent study showed that curcumin glucuronide has a less potent effect than curcumin itself on HepG2 cells, as the expression of GSTT1, CAT, IL-8, AREG, and ACOX1 genes was greatly downregulated by curcumin than by curcumin glucuronide. [43] In addition, curcumin is more rapidly absorbed than curcumin glucuronide. [43] Curcumin is the most studied natural product for HCC; it is clearly effective in HCC at different molecular mechanisms for inflammation, proliferation, and apoptosis, there is a lack of clinical data in humans to confirm the above.…”

Section: Curcuminmentioning

confidence: 99%

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Natural products and hepatocellular carcinoma: a review

Alnajjar¹,

Elsiesy²

2015

Hepatoma Res

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Hepatocellular carcinoma (HCC) is the fi fth commonest cause of malignancy and the third cause of cancer mortality. There are different treatment options for HCC ranging from loco-regional therapy to surgical treatment. Different regimen of systemic chemotherapy has been tried with a poor response. Several studies aimed at discovering more molecules for the management of HCC. Those studies aimed at recognizing and targeting several signaling and molecular pathways that lead to cellular proliferation and tumor formation. In this review, we discussed the role of several agents found in natural and dietary products such as curcumin, resveratrol, fl avonoids, Rubus aleaefolius Poir total alkaloids, Livistona chinensis seed, and crocetin. We had used the names of the above-mentioned products as key words in addition to "HCC" on PubMed to fi nd studies that discussed their roles in HCC. Articles were downloaded for reviewing and discussing natural products that had adequate studies in treating HCC.

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Comparison of the effects of curcumin and curcumin glucuronide in human hepatocellular carcinoma HepG2 cells

Cited by 79 publications

References 16 publications

Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways

Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways

Metabolic fate of poly-(lactic-co-glycolic acid)-based curcumin nanoparticles following oral administration

Natural products and hepatocellular carcinoma: a review

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