Analysis of Curcumin as a Radiosensitizer in Cancer Therapy with Serum Survivin Examination: Randomised Control Trial

Objective: One of the important treatments for cervical cancer is radiation therapy. This study sought to determine the role of curcumin as a radio-sensitizing agent for use with radiation therapy for cervical cancer. To accomplish this, we assessed the levels of survivin, which is an anti-apoptotic protein that plays a role in cell division and apoptosis inhibition. Method: This study used a quasi-experimental design, including a pretest–posttest control group design approach. The study subjects included cervical carcinoma stage IIB–IIIB patients who were scheduled to undergo surgery at the Hasan Sadikin Hospital Bandung during the research period. The advanced cervical cancer patients were assigned to two groups: i) those who received curcumin + radiation therapy and ii) those who received placebo + radiation therapy. Results: In the group treated with curcumin + radiation, 15 (75%) patients showed decreased survivin levels and 5 (25%) showed increased survivin levels. Whereas, in the placebo + radiation group, there were 8 (40%) patients who showed decreased survivin levels and 12 (60%) who showed increased survivin levels. Conclusion: In conclusion, curcumin is an effective, alternative radiosensitizer agent for application in cervical cancer treatment.     

Curcumin analog B14 has high bioavailability and enhances the effect of anti‐breast cancer cells in vitro and in vivo

Curcumin has a variety of anticancer properties, but low bioavailability prevents its use in chemotherapeutic applications. To address this problem, we tested the efficacy of the synthetic curcumin analog B14 in breast cancer cells and explored the mechanism by which B14 inhibits proliferation and metastasis of breast cancer cells. We used the breast cancer cell line MCF‐7, MDA‐MB‐231 to study the anticancer effects of B14 and assessed cell viability, cell migration and invasion, cell cycle, and apoptosis, in addition, the antitumor effect of B14 in vivo was examined in mice bearing MDA‐MB‐231 cells. We found that, as the concentration of B14 increased, cell viability decreased in a dose‐dependent manner. Compound B14 exerted the best antitumor activity and selectivity for MCF‐7 and MDA‐M‐231 cells (IC₅₀ = 8.84 μmol/L and 8.33 μmol/L, respectively), while its IC₅₀ value for MCF‐10A breast epithelial cells was 34.96 μmol/L. B14 has been shown to be a multi‐targeted drug that alters the expression of cyclin D1, cyclin E1, and cyclin‐dependent kinase 2 (CDK2), and ultimately induces G1 phase cell cycle arrest. At the same time, B14 activates the mitochondrial apoptosis pathway in breast cancer cells. Furthermore, B14 was more effective than curcumin in inhibiting cell migration, invasion, and colony formation. In tumor‐bearing mice, analog B14 significantly reduced tumor growth and inhibited cell proliferation and angiogenesis. The pharmacokinetic test found that B14 was more stable than curcumin in vivo. Our data reveal the therapeutic potential of the curcumin analog B14 and the underlying mechanisms to fight breast cancer cells.     

姜黄素抑制顺铂诱导人肾小管上皮细胞系HK-2凋亡

目的探讨姜黄素对顺铂诱导人肾小管上皮细胞系HK-2凋亡的影响。方法用MTT法观察HK-2增殖;用Western blot检测HK-2的凋亡蛋白。结果 1)顺铂呈剂量依赖性诱导HK-2凋亡(P<0.05)。2)在姜黄素和顺铂联合作用下,凋亡的HK-2明显减少,细胞存活率提高(P<0.05);HK-2中Bax蛋白表达降低(P<0.05);Bcl-2蛋白表达增加(P<0.05)。结论姜黄素可以通过调控Bax和Bcl-2蛋白的表达抑制顺铂引起的细胞凋亡。     

Curcumin reduces the expression of interleukin 1β and the production of interleukin 6 and tumor necrosis factor alpha by M1 macrophages from patients with Behcet's disease

Objective: Behcet's disease (BD) is an auto-inflammatory disorder. Curcumin as a bio-active agent has anti-inflammatory properties. Effects of curcumin on the pathogenesis of BD are still not clear. In this study, we investigated the effect of curcumin on the inflammatory cytokines expression and production in M1 macrophages from BD patients compared with healthy controls.

Methods: Monocytes were collected from 10 healthy controls and 20 active BD patients, differentiated to macrophages by macrophage-colony stimulating factor for 7?d. Macrophages were then treated with interferon gamma, lipopolysaccharide, and curcumin (10 or 30?µg/ml) for 24?h. Analysis of tumor necrosis factor-alpha (TNFα), interleukin 1β (IL-1β), and IL-6 mRNA expression and protein production was performed using SYBR Green qPCR and ELISA method.

Results: Treatment with 30?µg/ml curcumin significantly down-regulated mRNA expression of IL-1β (p?<?.05) and protein production of IL-6 (p?curcumin also significantly diminishes the protein production of TNFα in BD patients (p?p?Conclusions: We demonstrated that curcumin can inhibit the expression and production of inflammatory cytokines in M1 macrophages from BD patients. Our results suggest that curcumin can modulate inflammatory signaling more specifically in macrophages from BD patients than healthy macrophages.     

姜黄素联合顺铂对肺癌治疗的体外实验研究

目的探讨姜黄素(CUR)与化疗药(DDP)联合应用治疗肺癌的效应和可能机制。方法应用MTT试验检测CUR与DDP联用对人肺癌A549细胞增殖的影响,用流式细胞术检测CUR与DDP联用对人肺癌A549细胞周期和凋亡的影响。结果在一定的浓度范围内,随着姜黄素与顺铂均可抑制细胞生长,呈量-效关系。姜黄素与顺铂联用时,可以增强对A549细胞的增殖抑制作用。姜黄素和顺铂均可诱导A549细胞的凋亡,而且两者联用可增加A549细胞的凋亡率。姜黄素将细胞聚结在G2/M期并可诱导凋亡,顺铂将细胞聚结在S期并可诱导凋亡。结论姜黄素、顺铂均可抑制人肺腺癌A-549细胞的增殖、诱导细胞的凋亡,在一定浓度范围内,呈量-效关系,而且两者联合应用具有相加或协同作用。其效应可能是通过对细胞周期的影响来实现的。     

姜黄素降低Ⅲ型CP/CPPS模型鼠炎性反应因子的表达

目的研究姜黄素对Ⅲ型慢性前列腺炎/慢性骨盆疼痛综合征(CP/CPPS)模型鼠炎性反应因子表达的影响。方法将大鼠随机分为假手术组(sham)、CP/CPPS模型组(model)、姜黄素50及100 mg治疗组(cur-50 mg,cur-100 mg)和p38抑制剂组(SB203580),连续腹腔给药12 d后,real-time PCR检测前列腺组织中TNF-α、p38、COX-2的mRNA表达;免疫组化检测TNF-α,COX-2的蛋白表达;Western blot检测p38、p-p38和NF-κB蛋白的表达。结果 CP/CPPS模型组的NF-κB、p-p38、TNF-α和COX-2蛋白,TNF-α、COX-2和p38的mRNA表达较假手术组升高(P0.01);cur-100 mg组和SB203580组可显著缓解模型组的变化(P0.01);cur-100 mg组中的COX-2蛋白和mRNA均比SB203580组明显下降(P0.05);相较模型组,姜黄素2个组、SB203580组p-p38与NF-κB的表达呈正相关(P0.01)。结论姜黄素能够降低CP/CPPS模型鼠NF-κB、TNF-α和COX-2及p-p38等炎性反应因子的表达。     

Curcumin induces cell death of the main molecular myeloma subtypes,particularly the poor prognosis subgroups

Multiple myeloma (MM), a plasma cell malignancy, remains incurable despite the development of new therapies. Curcumin anti-tumor effects were previously characterized in multiple myeloma, however only few MM cell lines were included in these studies. Since myeloma is a heterogeneous disease it is important to address the impact of myeloma molecular heterogeneity in curcumin cell death induction. In the present study, a large panel of human myeloma cell lines (HMCLs) (n = 29), representing the main molecular MM subgroups, was screened for curcumin sensitivity. We observed that curcumin cell death induction was heterogeneous, of note 16 HMCLs were highly sensitive to curcumin (LD₅₀ < 20.5 μM), 6 HMCLs exhibited intermediate LD₅₀ values (20.5 μM ≤ LD₅₀ < 32.2 μM) and only 7 HMCLs were weakly sensitive (35 < LD₅₀ < 56 μM). Cell lines harboring the t(11;14) translocation were less sensitive (median LD50 32.9 μM) than non-t(11;14) (median LD50 17.9 μM), which included poor prognosis t(4;14) and t(14;16) cells. Interestingly, curcumin sensitivity was not dependent on TP53 status. For the first time we showed that primary myeloma cells were also sensitive, even those displaying del(17p), another poor prognosis factor. We also unravel the contribution of anti-apoptotic Bcl-2 family molecules in curcumin response. We found that down-regulation of Mcl-1, an essential MM survival factor, was associated with curcumin-induced cell death and its knockdown sensitized myeloma cells to curcumin, highlighting Mcl-1 as an important target for curcumin-induced apoptosis. Altogether, these results support clinical trials including curcumin in association with standard therapy.