Antitumor Effects Of Curcumin Research Articles

Mussel-inspired protein-based nanoparticles for curcumin encapsulation and promoting antitumor efficiency

Curcumin demonstrated therapeutic potential for cancer. However, its medical application is limited due to low solubility, poor stability and low absorption rate. Here, we used the mussel-inspired functional protein (MPKE) to fabricate the curcumin-carrying nanoparticle (Cur-MPKE) for encapsulating and delivering curcumin. The protein MPKE is composed of the mussel module and zwitterionic peptide. The Dopa group bonding characteristic of the mussel module was leveraged for the self-assembly of nanoparticles, while the superhydrophilic property of the zwitterionic peptide was utilized to enhance the stability of nanoparticles. As expected, MPKE and Cur are tightly bound through hydrogen bonds and dynamic imide bonds to form nanoparticles. Cur-MPKE showed improved solubility and stability in aqueous solutions as well as excellent biocompatibility. Besides, Cur-MPKE also exhibited pH-triggered release and enhanced uptake of curcumin by tumor cells, promoting the antioxidant activity and antitumor effect of curcumin. Moreover, systemic experiments of Cur-MPKE to rats demonstrated that Cur-MPKE significantly inhibited tumor tissue growth and proliferation without causing obvious systemic toxicity. This work provides a new strategy for fabricating the delivery system of curcumin with improved stability, sustainability and bioavailability.

Photostabilities and anti-tumor effects of curcumin and curcumin-loaded polydopamine nanoparticles.

Currently, the photostability of photosensitizer curcumin is the main bottleneck limiting their application, reducing the bioavailability of curcumin. Studying the effect of different light sources on the photostabilities of curcumin and loading it onto polydopamine nanocarriers with better biocompatibility will help improve its light utilization efficiency. In this study, we investigated the photostabilities of curcumin and a polydopamine-based nanoparticle (polydopamine-curcumin composite nanoparticles, PDA-Cur NPs) loaded with curcumin through in vitro and in vivo experiments to achieve better antitumor effects. The results demonstrated that curcumin has good photostability in dark, but with significant photodegradation rates in both red and blue light. Blue light has a faster effect on the photodegradation of curcumin, with a degradation rate of 42.1% after 10 minutes, which is about 1.7 times that of the red light. Our study successfully synthesized PDA-Cur NPs, demonstrating its ability to stably load and release curcumin, with a loading percentage of 65.7% after 2 hours and 41.9% release in 8 hours (pH 6.0). Compared with single curcumin treatments, the photodegradation rates of PDA-Cur NPs in red and blue light treatments were reduced by 46% and 50%, respectively. Meanwhile, PDA-Cur NPs exhibited remarkable antitumor efficacy due to PDT and promote apoptosis in cancer cells, which both better than that of single curcumin treatments. Moreover, in MCF-7 tumor-bearing mice, the PDA-Cur NPs led to significant tumor growth inhibition effects, without causing evident systemic damage in vivo. The findings highlight the potential of PDA-Cur NPs as anticancer photosensitizer with greatly increased utilization of curcumin in PDT.

Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling.

Curcumin is the most abundant derivative of turmeric rhizome. Although studies have proved that curcumin could inhibit the growth of tumors, its specific molecular mechanism has not yet been fully elucidated. This study aims to systematically elaborate the mechanisms of curcumin against hepatocellular carcinoma. The anti-tumor effect of curcumin was determined by the cell viability test. Flow cytometry was applied to examine the cell cycle and the apoptosis of cancer cells, and the cancer cell migration was detected by wound healing experiments. The expressions of signal transducers and activators of transcription 3 (STAT3), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in cancer cells were examined by immunostaining and analyzed by the Image J analysis system. After treatment with curcumin, the apoptosis ratio of HepG2 cells increased significantly (P < 0.05). The proliferation of cancer cells was arrested at the S-phase cell cycle, and the migration of cancer cells was inhibited by the increasing concentration of curcumin, together with the decreasing expressions of STAT3, VEGF, and HIF-1α signaling pathways. The results indicate that curcumin could effectively inhibit the growth and migration of hepatocarcinoma cells by inducing cancer cell apoptosis, blocking the cancer cell cycle in the S phase, and reducing the expression of STAT3, VEGF, and HIF-1α signaling pathways.

Pathological and Molecular Studies on Antitumor effect of Curcumin and Curcumin Solid Lipid Nanoparticles

Pathological and Molecular Studies on Antitumor effect of Curcumin and Curcumin Solid Lipid Nanoparticles

Nanogels loading curcumin in situ through microemulsion photopolymerization for enhancement of antitumor effects

Drug-loaded nanogels for cancer treatment can limit the free diffusion and distribution of drug molecules in the whole body to reduce undesirable side effects and improve the drug absorption efficiency of the tumor. In this study, curcumin as a model drug was encapsulated into nanogels in situ through microemulsion photopolymerization at 532 nm. Nanogels loaded with curcumin (NG-C) displayed a diameter of around 150 nm with good stability and a low polydispersity index of around 0.1. NG-C had a drug-loading capacity of 8.96 ± 1.16 wt%. The cumulative release of curcumin from NG-C was around 25%, 34% and 55% within 90 h in pH 7.4, 6.8 and 5.0 PBS buffer, respectively. NG-C presented prominent cytotoxicity toward Hep G2 and HeLa cancer cells in vitro. Moreover, NG-C exhibited much a stronger inhibition of tumor growth, necrosis, apoptosis, and the suppression of proliferation compared with curcumin on Hep G2 tumor-bearing nude mice.

Curcumin Mediates the Proliferation and Apoptosis of Colorectal Cancer Cells by Downregulating the Expression of Interleukin-1β through the Nuclear Factor-κB Signaling Pathway

Background: Colorectal cancer (CRC) is a frequently occurring malignant tumor, which is mainly observed in elderly men with no significant symptoms at the early stage. Among the malignant tumors of the digestive system, the incidence and mortality of CRC rank second only to hepatic and gastric cancer. Curcumin is an antioxidant and anti-inflammatory compound extracted from the roots of Curcuma longa plant. The antitumor effects of curcumin have been widely reported for various types of cancers, including CRC. Objective: In this study, we aimed to elucidate the protective effects and mechanism of interleukin (IL)-1 β on curcumin-induced apoptosis in SW480 cells. Materials and Methods: Expression levels of IL-1 β in CRC tissues and cells were detected by the quantitative reverse transcription polymerase chain reaction and Western blot assays. Followed by the incubation of cells with curcumin, the effect on IL-1 β was measured. Moreover, after transfection, the effects of IL-1 β on curcumin-induced SW480 cellular processes were analyzed by cell counting kit-8 and flow cytometric analysis. Results: According to the results of this study, IL-1 β was significantly increased in CRC tissues and cells. However, after incubation of the cells with curcumin, IL-1 β was downregulated and overexpression of IL-1 β counteracted the antitumor functions of curcumin in SW480 cells. Further studies have shown that curcumin could promote apoptosis of SW480 cells by inhibiting nuclear factor-κB (NF-κB) signaling pathway. Conclusion: Our study validated that curcumin inhibits SW480 cell proliferation but promotes apoptosis by downregulating the expression of IL-1 β probably through NF-κB signaling pathway. IL-1 β may an important target for the treatment of CRC.

Curcumin suppresses colorectal tumorigenesis via the Wnt/β-catenin signaling pathway by downregulating Axin2.

Colorectal cancer (CRC) is the third most common cancer worldwide, with high incidence and mortality rates. Conventional therapies, including surgery, chemotherapy and radiation, are extensively used for the treatment of CRC. However, patients present with adverse effects, such as toxicity, hepatic injury and drug resistance. Thus, there is an urgent requirement to identify effective and safe therapy for CRC. Curcumin (CUR), a polyphenol substrate extracted from the rhizome of Curcuma longa, has been extensively studied for the treatment of CRC due to its high efficacy and fewer side effects. Previous studies have reported that several signaling pathways, such as NF-κB, Wnt/β-catenin, are involved in the antitumor effects of CUR in vitro. However, the effect and mechanisms in vivo are not yet fully understood. The present study aimed to determine the molecular mechanism of colorectal cancer in vivo. Reverse transcription-quantitative PCR, western blot and immunohistochemistry analyses were performed to determine the underlying molecular mechanism of curcumin's anti-cancer effect in azoxymethane-dextran sodium sulfate induced colorectal cancer. The results of the present study demonstrated that CUR suppressed tumorigenesis in AOM-DSS induced CRC in mice, and anticancer effects were exerted by suppressing the expression of pro-inflammatory cytokines, and downregulating Axin2 in the Wnt/β-catenin signaling pathway. Taken together, these results exhibit the potential in vivo mechanisms of the anticancer effects of CUR, and highlight Axin2 as a potential therapeutic target for CRC.

Antitumor effects of curcumin in pediatric rhabdomyosarcoma in combination with chemotherapy and phototherapy invitro.

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, has an unfavorable outcome in advanced tumor stages with less than 30%failure‑free survival. Curcumin (CUR) is a promising drug in complementary oncology with few side effects but proven efficacy in various adult oncological entities. The present study analyzed the effects of CUR on pediatric (RMS) cell lines invitro. RMS cell lines (RD and RH30), and skeletal muscle cells (SKMC) were treated with different doses of CUR (1.5‑30µM) alone, with phototherapy (PDT, 488nm) or in combination with vincristine (VCR) or dactinomycin (DAC). MTT assays were used for analysis of RMS tumor cell viability. Clonal cell growth was assessed via colony forming assays and migration of the cells was analyzed with scratch tests. Annexin V staining was used to determine apoptosis in flow cytometry. Possible RMS resistance towards CUR after long‑term treatment was analyzed with MTT assays. CUR decreased cell viability in all assessed RMS cell lines in a concentration‑dependent manner with IC50=14‑20µM. CUR enhanced the effects of the cytotoxic drugs VCR or DAC, and led to reduced migration and increased cell apoptosis. In combination with PDT, CUR decreased the cell viability in minute quantities with up to a 10‑fold lower IC50 than without PDT. CUR effectively inhibited the malignant properties of pediatric RMS cells and should be focused on as a useful additional agent in standard chemotherapy of RMS in children.

Antitumor effects of curcumin on the proliferation, migration and apoptosis of human colorectal carcinoma HCT‑116 cells.

Curcumin is the main component of the Chinese herbal plant turmeric, which has been demonstrated to possess antitumor and other pharmacological properties. The aim of the present study was to investigate the effects of curcumin on the viability, migration and apoptosis of human colorectal carcinoma HCT-116 cells, and to explore the underlying molecular mechanisms. In addition, it was investigated whether the antitumor effect of curcumin on HCT-116 cells could match that of the chemotherapeutic drug 5-fluorouracil (5-FU). HCT-116 cells were treated with curcumin (10, 20 and 30 µM) and 5-FU (500 µM), and cell viability and proliferation were detected by Cell Counting Kit-8 and colony formation assays, respectively. The migration and invasion of treated cells were determined using Transwell and carboxyfluorescein succinimidyl amino ester fluorescent labeling assays. Cell cycle distribution and apoptosis rates were detected by flow cytometry. Furthermore, cell morphology changes associated with apoptosis were observed by fluorescence microscopy with acridine orange/ethidium bromide dual staining. To investigate the possible underlying molecular mechanisms, the gene and protein levels of Fas, Fas-associated via death domain (FADD), caspase-8, caspase-3, matrix metalloproteinase (MMP)-9, nuclear factor (NF)-κB, E-cadherin and claudin-3 were detected using quantitative PCR analysis, zymography and western blotting. The results revealed that curcumin markedly inhibited the viability and proliferation of HCT-116 cells in a dose- and time-dependent manner. The migration, aggregation and invasion of HCT-116 cells into the lungs of mice were decreased by curcumin treatment in a dose-dependent manner. S-phase arrest and gradually increased apoptotic rates of HCT-116 cells were observed with increasing curcumin concentrations. Additionally, the mRNA and protein levels of apoptosis-associated proteins (Fas, FADD, caspase-8 and caspase-3) and E-cadherin in HCT-116 cells were upregulated following treatment with curcumin in a dose-dependent manner. By contrast, the expression of migration-associated proteins, including MMP-9, NF-κB and claudin-3, was downregulated with increasing curcumin concentrations. These data suggested that the inhibitory effect of curcumin on HCT-116 cells may match that of 5-FU. Therefore, curcumin induced cell apoptosis and inhibited tumor cell metastasis by regulating the NF-κB signaling pathway, and its therapeutic effect may be comparable to that of 5-FU.

Antitumor Effects of Curcumin and Glycyrrhetinic Acid-Modified Curcumin-Loaded Cationic Liposome by Intratumoral Administration.

Curcumin is a hydrophobic polyphenolic compound extracted from the rhizome of Curcuma longa and shows a line of active biological functions, but its application has been limited and questioned because of its low solubility, low bioavailability, and rapid metabolism. In terms of antitumor effect, these disadvantages can be overcome by intratumoral injection. In this study, we present the intratumoral injection of curcumin and glycyrrhetinic acid-modified curcumin-loaded cationic liposome (GAMCLCL) in H22 tumor-bearing mice. The experimental results demonstrated that curcumin exhibited positive antitumor activities in vitro and in vivo by intratumoral injection, but its activities were much weaker than GAMCLCL and adriamycin. Compared with free curcumin, GAMCLCL showed much better effects in improving the blood parameters (WBC, RBC, PLT, ALT, CRE, and LDH), inhibiting tumor growth, reducing tumor microvascular density, downregulating the expression of VEGF-protein and mRNA, and upregulating the expression of caspase-3 protein and mRNA in H22 tumor tissues. Under the experimental conditions of this study, the antitumor effect of high-dose GAMCLCL was similar to adriamycin. In conclusion, the experimental results demonstrated that free curcumin possessed definite antitumor efficacy, but its antitumor activities were weaker, and some strategies should be adopted to overcome its disadvantages, improve, and ensure its clinical efficacy.

Development of curcumin-loaded methoxy poly(ethylene glycol)-block- poly(caprolactone)-block-poly(1, 4, 8-Trioxa [4.6] spiro-9-undecanone) nanoparticles and studies on their in vitro anti-tumor activities

The purpose of this paper was to fabricate a novel methoxy poly(ethylene glycol)-block-poly(caprolactone)-block-poly(1, 4, 8-Trioxa [4.6] spiro-9-undecanone) (mPEG-b-PCL-b-PTOSUO, mPECT) triblock copolymer and study on the in vitro anti-tumor activity of curcumin-loaded mPECT nanoparticles (NPs). The mPEG-b-PCL-b-PTOSUO NPs were fabricated with solvent evaporation. Transmission electron microscope (TEM) and laser particle analyzer were applied to investigate the morphology and size distribution of the obtained mPECT NPs. The cytotoxicity of the copolymer (mPECT) was reflected by cell viability. Curcumin (CUR), as a model drug, was encapsulated into mPECT NPs. The in vitro anti-tumor activity of CUR-loaded mPECT NPs were also studied. 1H nuclear magnetic resonance (1H NMR), Raman, and Fourier transform infrared spectroscopy (FTIR) spectra confirmed the obtaining of mPECT. TEM photograph showed that most of mPECT NPs were in spherical shapes with a uniform size distribution. High cell viability suggested that the cargo-free mPECT NPs had no obvious cytotoxicity. Fluorescent photographs illustrated that CUR-loaded mPECT NPs could be up-taken by SW1990 cells. The medicated NPs could inhibit the proliferation of SW1990 cells. Therefore, the mPECT NPs could be used as a vehicle to improve the bioavailability and anti-tumor effects of CUR.

Inhibitory effect and mechanism of curcumin on tumor tissues of breast cancer mice

Objective To study the anti-tumor effect of curcumin on breast cancer mice and its mechanism. Methods 4T1 mouse breast cancer cells were inoculated into mammary at pad of BALB/c mice for establishing the breast cancer mouse model. The tumor-bearing mice were divided into model group and curcumin low, medium and high dose (25, 50, 100 mg/kg) group. After 4 weeks of continuous administration, the tumor inhibition rate, spleen index and thymus index were calculated. The serum contents of interleukin-2 (IL-2), interleukin-12 (IL-12) and interleukin-α (TNF-α) were detected by enzyme-linked immunosorbent assay. The protein expression of phosphoinositide 3-kinase (PI3K), serine-threonine kinase (Akt), mammalian target of rapamycin (mTOR) and phosphorylation levels were detected by Western blotting. The effects of insulin-like growth factors-1 (IGF-1) which could activate PI3K, LY294002 which could inhibit PI3K and curcumin on the activity of mouse breast cancer cell 4T1 was detected by CCK-8 method, and to explore the effects of IGF-1, LY294002 and curcumin on PI3K/Akt/mTOR signaling pathway in 4T1 cells. Measurement data were expressed as Mean±SD, and t-test was used for comparison between groups. Results The tumor weight [(0.91±0.21), (0.83±0.18) vs. (1.18±0.24) g, t=2.820, P<0.05; t=3.846, P<0.01] of curcumin medium, high dose groups was lower than model group, and the tumor inhibition rate was 22.88% and 29.66%. The spleen index [(71.37±8.54), (75.79±8.87) vs. (63.21±5.74) mg/10 g, t=2.398, P<0.01; t=3.628, P<0.01 of curcumin medium, high dose groups and the thymus index [(28.46±4.74) vs. (23.33±2.78) mg/10g, t=3.254, P<0.01] of high dose group were higher than model group. The serum IL-2 contents [(139.55±16.95), (146.78±17.21) vs. (120.46±15.45) ng/L, t=2.819, P<0.05; t=3.859, P<0.01] and TNF-α contents [(53.46±6.89), (57.19±7.01) vs. (46.57±6.32) ng/L, t=2.493, P<0.05; t=3.811, P<0.01] of curcumin medium, high dose groups, and IL-12 contents [(163.24±18.73) vs. (148.26±16.31) ng/L, t=2.340, P<0.05] of high dose group were higher than model group. The p-Akt levels in tumor tissue [(0.69±0.12), (0.62±0.08) vs. (0.83±0.14), t=2.405, P<0.05; t=4.161, P<0.01] of curcumin medium, high dose groups, and p-PI3K levels [(0.62±0.11) vs. (0.75±0.13), t=2.537, P<0.05], p-mTOR levels [(0.56±0.11) vs. (0.69±0.17), t=2.098, P<0.05] were lower than the model group. The cell viability of 4T1 was 211.40%, 36.40% and 63.93% (t=11.890, P<0.01; t=16.160, P<0.01; t=8.742, P<0.01) after intervention with IGF-1, LY294002 and curcumin (100 μmol/L). The levels of p-PI3K, p-Akt and p-mTOR were increased in IGF-1 group (0.942±0.081, 0.894±0.093, 0.831±0.065, t=5.257, P<0.01; t=5.144, P<0.01; t=7.166, P<0.01) and IGF-1+ curcumin group (0.759±0.061, 0.751±0.058, 0.682±0.047, t=2.801, P<0.05; t=3.029, P<0.05; t=3.512, P<0.01) compared with the negative control group (0.671±0.082, 0.633±0.065, 0.583±0.042). Compared with the IGF-1 group, the levels of p-PI3K (t=3.153, P<0.05), p-Akt (t=2.917, P<0.05) and p-mTOR (t=4.154, P<0.01) in IGF-1+ curcumin group were decreased. Conclusion Curcumin can inhibit the breast cancer in mice and improve the immunity of the body, and its anti-tumor mechanism may be related to inhibition of PI3K/Akt/mTOR signaling pathway. Key words: Curcumin; Mouse breast cancer; Phosphoinositide 3-kinase/serine-threonine kinase/mammalian target of rapamycin signaling pathway

Curcumin-Induced Autophagy Augments Its Antitumor Effect against A172 Human Glioblastoma Cells.

Glioblastoma is the most aggressive common brain tumor in adults. Curcumin, from Curcuma longa, is an effective antitumor agent. Although the same proteins control both autophagy and cell death, the molecular connections between them are complicated and autophagy may promote or inhibit cell death. We investigated whether curcumin affects autophagy, which regulates curcumin-mediated tumor cell death in A172 human glioblastoma cells. When A172 cells were incubated with 10 μM curcumin, autophagy increased in a time-dependent manner. Curcumin-induced cell death was reduced by co-incubation with the autophagy inhibitors 3-methyladenine (3-MA), hydroxychloroquine (HCQ), and LY294002. Curcumin-induced cell death was also inhibited by co-incubation with rapamycin, an autophagy inducer. When cells were incubated under serum-deprived medium, LC3-II amount was increased but the basal level of cell viability was reduced, leading to the inhibition of curcumin-induced cell death. Cell death was decreased by inhibiting curcumin-induced autophagy using small interference RNA (siRNA) of Atg5 or Beclin1. Therefore, curcumin-mediated tumor cell death is promoted by curcumin-induced autophagy, but not by an increase in the basal level of autophagy in rapamycin-treated or serum-deprived conditions. This suggests that the antitumor effects of curcumin are influenced differently by curcumin-induced autophagy and the prerequisite basal level of autophagy in cancer cells.

Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer.

Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

The Antitumor Effect of Curcumin in Urothelial Cancer Cells Is Enhanced by Light Exposure In Vitro.

The natural compound curcumin exerts antitumor properties in vitro, but its clinical application is limited due to low bioavailability. Light exposure in skin and skin cancer cells has been shown to improve curcumin bioavailability; thus, the object of this investigation was to determine whether light exposure might also enhance curcumin efficacy in bladder cancer cell lines. RT112, UMUC3, and TCCSUP cells were preincubated with low curcumin concentrations (0.1-0.4 μg/ml) and then exposed to 1.65 J/cm2 visible light for 5 min. Cell growth, cell proliferation, apoptosis, cell cycle progression, and cell cycle regulating proteins along with acetylation of histone H3 and H4 were investigated. Though curcumin alone did not alter cell proliferation or apoptosis, tumor cell growth and proliferation were strongly blocked when curcumin was combined with visible light. Curcumin-light caused the bladder cancer cells to become arrested in different cell phases: G0/G1 for RT112, G2/M for TCCSUP, and G2/M- and S-phase for UMUC3. Proteins of the Cdk-cyclin axis were diminished in RT112 after application of 0.1 and 0.4 μg/ml curcumin. Cell cycling proteins were upregulated in TCCSUP and UMUC3 in the presence of 0.1 μg/ml curcumin-light but were partially downregulated with 0.4 μg/ml curcumin. 0.4 μg/ml (but not 0.1 μg/ml) curcumin-light also evoked late apoptosis in TCCSUP and UMUC3 cells. H3 and H4 acetylation was found in UMUC3 cells treated with 0.4 μg/ml curcumin alone or with 0.1 μg/ml curcumin-light, pointing to an epigenetic mechanism. Light exposure enhanced the antitumor potential of curcumin on bladder cancer cells but by different molecular action modes in the different cell lines. Further studies are necessary to evaluate whether intravesical curcumin application, combined with visible light, might become an innovative tool in combating bladder cancer.

Antitumor effects of curcumin: A lipid perspective.

Lipid metabolism plays an important role in cancer development due to the necessities of rapidly dividing cells to increase structural, energetic, and biosynthetic demands for cell proliferation. Basically, obesity, type 2 diabetes, and other related diseases, and cancer are associated with a common hyperactivated "lipogenic state." Recent evidence suggests that metabolic reprogramming and overproduction of enzymes involved in the synthesis of fatty acids are the new hallmarks of cancer, which occur in an early phase of tumorigenesis. As the first evidence to confirm dysregulated lipid metabolism in cancer cells, the overexpression of fatty acid synthase (FAS) was observed in breast cancer patients and demonstrated the role of FAS in cancer. Other enzymes of fatty acid synthesis have recently been found to be dysregulated in cancer, including ATP-dependent citrate lyase and acetyl-CoA carboxylase, which further underscores the connection of these metabolic pathways with cancer cell survival and proliferation. The degree of overexpression of lipogenic enzymes and elevated lipid utilization in tumors is closely associated with cancer progression. The question that arises is whether the progression of cancer can be suppressed, or at least decelerated, by modulating gene expression related to fatty acid metabolism. Curcumin, due to its effects on the regulation of lipogenic enzymes, might be able to suppress, or even cause regression of tumor growth. This review discusses recent evidence concerning the important role of lipogenic enzymes in the metabolism of cancer cells and whether the inhibitory effects of curcumin on lipogenic enzymes is therapeutically efficacious.

Curcumin-induced promoter hypermethylation of the mammalian target of rapamycin gene in multiple myeloma cells.

Curcumin, a polyphenol derived from the rhizome of Curcuma, is a potential tumor inhibitor through affecting signaling pathways and epigenetic regulation. The mammalian target of rapamycin (mTOR) gene serves a crucial role in the carcinogenesis of multiple myeloma. The curcumin-induced epigenetic regulation of mTOR, including promoter DNA methylation in multiple myeloma, has not yet been fully elucidated. In the present study, antitumor effects of curcumin were investigated in RPMI-8226 and NCI-H929 cells using an MTT assay and flow cytometry. The expression of mTOR and DNA methyltransferase proteins were determined by western blot analysis, and the methylation status of the mTOR promoter were detected by sequencing following bisulfite conversion. The results of the present study revealed that the half-maximal inhibitory concentration of curcumin was 10 µM in myeloma cells. Following curcumin treatment, the mRNA and protein expression levels of mTOR were decreased by 43.31 and 39.34% in NCI-H929 cells, respectively. The promoter of mTOR, located in chromosome 1 (chromosome position, 11262153-11263153), contains a CpG island that was hypermethylated in myeloma cells following curcumin treatment. The expression levels of DNA methyltransferase (DNMT)3a and DNMT3b were increased in curcumin-treated cells. Collectively, these results indicate that curcumin serves a role in the epigenetic regulation of mTOR expression, and that mTOR downregulation is due to promoter hypermethylation, which may be associated with DNMT3a and DNMT3b upregulation. The results of the present study contribute towards improving the understanding of curcumin treatment in multiple myeloma and provide novel insights into the molecular mechanisms underlying the epigenetic regulation of mTOR.

Curcumin inhibits proliferation and promotes apoptosis of breast cancer cells.

Curcumin is a natural compound that appears to be promising for clinical application, as it has been shown in in vitro and in vivo studies to exert antitumor effects by modulating multiple signaling cellular pathways. In the present study, the antitumor effects of curcumin and its mechanism of action were investigated in cultured breast cancer cells. The MTT assay was used to determine the effect of curcumin on breast cancer cell proliferation, flow cytometry was used to detect alterations of the cell cycle, and western blot analysis was used to determine the expression of signaling molecules involved in the cell cycle, proliferation and apoptosis. The results revealed that curcumin significantly inhibited the proliferation of various breast cancer cell lines, such as T47D, MCF7, MDA-MB-231 and MDA-MB-468, with an IC50 at the micromolar level, indicating the potent antitumor activity of curcumin. In-depth study of its mechanism of action revealed that curcumin induced cell cycle arrest at the G2/M phase and decreased the expression of the CDC25 and CDC2 proteins, while increasing the expression of P21. In addition, curcumin inhibited the phosphorylation of protein kinase B (Akt)/mammalian target of rapamycin (mTOR), decreased B-cell lymphoma 2 (BCL2) and promoted BCL-2-associated X protein (BAX) and cleavage of caspase 3, subsequently inducing apoptosis of breast cancer cells. In conclusion, curcumin inhibited the proliferation of breast cancer cells and induced G2/M phase cell cycle arrest and apoptosis, which may be associated with the decrease of CDC25 and CDC2 and increase of P21 protein levels, as well as inhibition of the phosphorylation of Akt/mTOR and induction of the mitochondrial apoptotic pathway. The findings of the present study may provide a basis for the further study of curcumin in the treatment of breast cancer.

Curcumin inhibits liver cancer by inhibiting DAMP molecule HSP70 and TLR4 signaling.

Curcumin has been revealed to inhibit liver cancer, however, no studies have reported that the mechanism of curcumin's action on liver cancer is related to damage-associated molecular pattern (DAMP) molecules heat shock protein70 (HSP70) and the toll-like receptor 4 (TLR4) signaling. This study aimed to investigate whether the activation of TLR4 signaling by HSP70 could be inhibited by curcumin, thus investigating the possible mechanism of curcumin in the inhibition of liver cancer. Western blotting was used to evaluate the expression of the HSP70 and TLR4 in HepG2 cells and ELISA was used to detect the concentration of HSP70 in cell culture medium. A thermal tolerance HepG2 (HepG2TT) cell model was established to simulate HSP70 accumulation in the microenvironment. A certain concentration of curcumin was co-cultured with HepG2 and HepG2TT cells to observe the changes of HSP70 and TLR4. Our results revealed that heat stress significantly increased the expression of extracellular HSP70 (eHSP70) and TLR4 (P<0.01), but significantly reduced the expression of intracellular HSP70 (P<0.01). Curcumin inhibited proliferation, invasion, and metastasis of HepG2 cells, caused cells to remain in the DNA Sphase, promoted apoptosis, and significantly reduced intracellular HSP70, eHSP70 and TLR4 levels of HepG2TT cells. Following the removal of curcumin, eHSP70 increased again. In summary, our results demonstrated that the antitumor effect of curcumin was related to the inhibition HSP70-TLR4 signaling.

Antitumor effects of curcumin in human bladder cancer in vitro.

Bladder cancer is one of the major causes of cancer-associated mortality, with a high incidence. Curcumin, a polyphenol compound extracted from turmeric, has been identified to regulate tumor progression. However, the therapeutic effect of curcumin in human bladder cancer has not yet been determined. In the present study, the effects of curcumin on cell growth, apoptosis and migration of bladder cancer cell lines were evaluated using an MTT assay, a Transwell assay and flow cytometry, and the associated mechanisms were investigated using western blot analysis. Curcumin was identified to decrease the growth of T24 and 5637 cells in a dose- and time-dependent manner. The present study confirmed that curcumin is able to inhibit cell migration and promote apoptosis of bladder cancer through suppression of matrix metalloproteinase signaling pathways in vitro. The anticancer effects of curcumin on bladder cancer cells may benefit clinical practice in the future.