Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells

Lev-Ari, Shahar; Strier, Ludmila; Kazanov, Diana; Elkayam, Ori; Lichtenberg, Dov; Caspi, Dan; Arber, Nadir

doi:10.1093/rheumatology/kei132

Cited by 78 publications

(33 citation statements)

References 49 publications

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“…growing evidence revealed that apoptosis was essential for cancer therapy and represents a mechanism to counteract neoplastic development (27,28). In recent years, accumulating studies on apoptosis have demonstrated that curcumin was responsible for inducing apoptosis signals in various tumor tissues, including lung cancer (27). Our study showed that Cur-NLC induced more apoptosis than native curcumin, which was consistent with the results of the cytotoxicity assay.…”

Section: Cur-nlc Induce Apoptosis In the A549 Cell Line In Vitrosupporting

confidence: 89%

“…These data revealed that both necrosis and apoptosis contributed to Cur-NLC induced death of A549 cells, and Cur-NLC treated A549 cells showed a higher apoptosis rate than that of native curcumin. growing evidence revealed that apoptosis was essential for cancer therapy and represents a mechanism to counteract neoplastic development (27,28). In recent years, accumulating studies on apoptosis have demonstrated that curcumin was responsible for inducing apoptosis signals in various tumor tissues, including lung cancer (27).…”

Section: Cur-nlc Induce Apoptosis In the A549 Cell Line In Vitromentioning

confidence: 99%

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Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

et al. 2017

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Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriersIn order to investigate the potential of nanostructured lipid carriers for efficient and targeted delivery of curcumin, the pharmacokinetic parameters of curcumin-loaded nanostructured lipid carriers (Cur-NLC) were evaluated in rats after a single intraperitoneal dose of Cur-NLC. In addition, the anticancer activity of Cur-NLC against human lung adenocarcinoma A549 cells was verified by a cellular uptake study, and a cytotoxicity and apoptosis assay. Bioavailability of Cur-NLC was better than that of native curcumin (p > 0.01), as seen from the area under the plasma concentration-time curve (AUC), maximum plasma concentration (C max) , mean residence time (MRT) and total plasma clearance (CL z /F).Cur-NLC has a more obvious lung-targeting property in comparison with native curcumin. Cur-NLC showed higher anticancer activity in vitro against A549 cells than native curcumin (IC 50 value of 5.66 vs. 9.81 mg L -1 , respectively). Meanwhile, Cur-NLC treated A549 cells showed a higher apoptosis rate compared to that of native curcumin. These results indicate that NLC is a promising system for the delivery of curcumin in the treatment of lung adenocarcinoma.Keywords: curcumin, nanostructured lipid carriers, pharmacokinetic, anticancer effects, lung adenocarcinoma Lung cancer is by far the most frequent cause of cancer-related deaths worldwide (1). The effectiveness of chemotherapeutic agents is often limited by the unavoidable toxicity of drug treatment. It is therefore essential to discover potential agents with more efficient therapeutic strategies and less severe side effects for the treatment of lung cancer. Phytochemicals have been gaining increasing attention as chemopreventive agents to treat various diseases, including lung cancer. Curcumin (C 21 H 20 O 6 ), a hydrophobic polyphenol, is an important phytochemical compound that gives the Asian spice turmeric its light yellow color. It is derived from the rhizome of Curcuma longa and has been long used as food color or for medication purposes worldwide, especially in India and other east Asian countries. 77 % curcumin I (diferuloylmethane), 17 % curcumin II (demethoxycurcumin) and 3 % curcumin III (bis-demethoxycurcumin) are the three major constituents of curcumin. Studies have indicated that curcumin has cancer preventive activity, either alone or in combination with other anticancer agents. Curcumin's widespread availability, safety, low cost and multiple cancer fighting functions make it a promising drug for the treatment of numerous cancers, including lung, cervical, breast, hepatic, pancreatic and colon cancer (2-5). The most attractive and vital reason for the therapeutic use of curcumin is its superior safety profile. It has been demonstrated that curcumin has very low toxicity, even at very high doses (6). Nevertheless, native curcumin cannot reach the therapeutic target in a therapeutic concentration because of its low bioavailability. Therefore, curcumin sho...

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Section: Cur-nlc Induce Apoptosis In the A549 Cell Line In Vitrosupporting

confidence: 89%

Section: Cur-nlc Induce Apoptosis In the A549 Cell Line In Vitromentioning

confidence: 99%

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

et al. 2017

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“…However, recent studies have shown that their long-term use may be limited due to cardiovascular toxicity (Kean and Buchanan, 2005). Whether curcumin can augment the growth-inhibitory and pro-apoptotic effects of celecoxib in OA synovial adherent cells was examined by Lev-Ari et al (2006). OA synovial adherent cells were prepared from human synovial tissue collected during total knee replacement surgery.…”

Section: Role Of Curcumin In the Treatment Of Chronic Inflammatorymentioning

confidence: 99%

Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases

Aggarwal

Harikumar

2009

The International Journal of Biochemistry & Cell Biology

1,630

949

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Although safe in most cases, ancient treatments are ignored because neither their active component nor their molecular targets are well defined. This is not the case, however, with curcumin, a yellowpigment substance and component of turmeric (Curcuma longa), which was identified more than a century ago. For centuries it has been known that turmeric exhibits anti-inflammatory activity, but extensive research performed within the past two decades has shown that the this activity of turmeric is due to curcumin, a diferuloylmethane. This agent has been shown to regulate numerous transcription factors, cytokines, protein kinases, adhesion molecules, redox status and enzymes that have been linked to inflammation. The process of inflammation has been shown to play a major role in most chronic illnesses, including neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases. In the current review, we provide evidence for the potential role of curcumin in the prevention and treatment of various pro-inflammatory chronic diseases. These features, combined with the pharmacological safety and negligible cost, render curcumin an attractive agent to explore further.

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“…Previously we had reported that , in vitro, low concentrations of curcumin (10–15 µmol/l) in combination with a physiologic concentration of celecoxib (5 µmol/l) is sufficient for inhibiting the growth of CRC and pancreatic cancer cells as well as synovial cells derived from patients with osteoarthritis, by inhibition of proliferation and induction of apoptosis through COX-2 and non-COX-2 pathways [16,17,18]. This growth inhibition effect is similar to that achieved with a 10-fold higher concentration of celecoxib (50 µmol/l) when administered alone.…”

Section: Discussionmentioning

confidence: 99%

“…Among the many mechanisms explaining its anticancer effects, curcumin can interfere with the activity of the transcription factor NF-ĸB, suppress EGFR gene expression, inhibit β-catenin-mediated transactivation and COX-2 expression [14, 15]. Recently, we showed the synergistic growth inhibition effect of celecoxib and curcumin in in vitromodels of cancer and inflammation [16,17,18]. The present study confirms the data collected in vitro in an in vivomodel of CRC, demonstrating that celecoxib and curcumin additively inhibit the growth of CRC in the 1,2-dimethylhydrazine (DMH) rat model.…”

Section: Introductionmentioning

confidence: 99%

Celecoxib and Curcumin Additively Inhibit the Growth of Colorectal Cancer in a Rat Model

et al. 2006

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Background: Multiple studies have indicated that specific COX-2 inhibitors may prevent CRC. However, the long-term use of COX-2 inhibitors is not toxicity-free and may be limited due to its cardiovascular side effects. The present study was carried out to examine the chemopreventive effects of celecoxib and curcumin alone and in combination using the 1,2-dimethylhydrazine (DMH) rat model. Methods: Male rats were injected with DMH and randomly divided into four groups that consumed one of the following diets: (a) AIN-076 control diet; (b) AIN-076/curcumin (0.6%); (c) AIN-076/celecoxib (0.16%), or (d) AIN-076/celecoxib (0.16%) and curcumin (0.6%). Aberrant crypt foci (ACF) were identified by intensive staining with methylene blue in comparison to the surrounding normal crypts. Results: The average number of ACF per rat colon was 64.2 ± 3 in the control group, 39 ± 5 and 47 ± 10 for the curcumin- and celecoxib-treated group, respectively, and 24.5 ± 6 in the group that had received both agents. Conclusions: In vivo, curcumin augments the growth inhibitory effect of celecoxib. This may be clinically important as this dose of celecoxib can be achieved in human serum following standard anti-inflammatory dosing of 100 mg.

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Curcumin synergistically potentiates the growth-inhibitory and pro-apoptotic effects of celecoxib in osteoarthritis synovial adherent cells

Abstract: This effect may enable the use of celecoxib at lower and safer concentrations, and may pave the way for a novel combination treatment in osteoarthritis and other rheumatological disorders.

Cited by 78 publications

References 49 publications

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

Pharmacokinetic studies and anticancer activity of curcumin-loaded nanostructured lipid carriers

Potential therapeutic effects of curcumin, the anti-inflammatory agent, against neurodegenerative, cardiovascular, pulmonary, metabolic, autoimmune and neoplastic diseases

Celecoxib and Curcumin Additively Inhibit the Growth of Colorectal Cancer in a Rat Model

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