demethoxycurcumin and Neoplasms

Curcumin (CU), an edible natural pigment from Curcuma Longa, has demonstrated extensive anti-tumor effect in vivo and in vitro. With the property of reversing drug resistance and low toxicity, CU has been considered to develop a new adjuvant chemotherapy protocol of cancer. However, the poor stability, solubility, in vivo bioavailability and weak activity of CU greatly limit its clinical application. Therefore, CU analogues have been extensively studied. Starting from the study of natural CU analogues, multiple approaches are being sought to obtain more stable, soluble and effective analogues of CU. This review focuses on the progress of these approaches to more potent CU analogues.

Topics: Animals; Antineoplastic Agents, Phytogenic; Cell Proliferation; Curcumin; Humans; Neoplasms

The eradication of cancer in a patient remains an elusive challenge despite advances in early detection and diagnosis, chemo- and immunotherapy, pinpoint radiation treatments, and expert surgical intervention. Although significant gains have been made in our understanding of cancer cell biology, a definite cure for most cancers does not exist at present. Thus, it is not surprising that the research and medical communities continue to explore the importance and therapeutic potential of natural products in their multimodality cancer treatment approach. Curcuminoids found in turmeric are one such class of natural products that have been extensively investigated for their potential to halt the progression of cancer cell proliferation and, more important, to stop metastasis from occurring. In this review, we examine one curcuminoid (demethoxycurcumin [DMC]) largely because of its increased stability and better aqueous solubility at physiological pH, unlike the more well-known curcuminoid (curcumin), which is largely unabsorbed after oral ingestion. The present review will focus on the signaling pathways that DMC utilizes to modulate the growth, invasion, and metastasis of cancer cells in an effort to provide enhanced mechanistic insight into DMC's action as it pertains to brain, ovarian, breast, lung, skin, and prostate cancer. Additionally, this review will attempt to provide an overview of DMC's mechanism of action by modulating apoptosis, cell cycle, angiogenesis, metastasis, and chemosensitivity. Lastly, it is hoped that increased understanding will be gained concerning DMC's interactive role with microRNA-551a, 5' adenosine monophosphate-activated protein kinase, nuclear factor-κB, Wnt inhibitory factor-1, and heat shock protein 70 to affect the progression of cancer.

Topics: AMP-Activated Protein Kinases; Apoptosis; Cell Proliferation; Curcumin; Diarylheptanoids; Gene Expression Regulation, Neoplastic; Humans; Neoplasms; NF-kappa B; Signal Transduction

Topics: Animals; Antineoplastic Agents; Carcinoma, Ehrlich Tumor; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Curcumin; Drug Screening Assays, Antitumor; Female; Humans; Male; Mice; Microtubules; Neoplasms

Three curcuminoids: bisdemethoxycurcumin, demethoxycurcumin, and curcumin from turmeric were successfully separated by a high capacity solvent system composed of heptane: chloroform: methanol: water mixture (5: 6: 3: 2 v/v/v/v) tailored for centrifugal partition chromatographs at K-values of 0.504, 1.057, 1.644, respectively. These three ferulic acid derivatives obtained at a purity rate exceeding 95% were analysed by an HPLC-MS spectrometer. Turmeric extract inhibited the proliferation/viability of A549 human lung cancer, HT29 colon cancer, and T98G glioblastoma cell lines in (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay (MTT). Single curcuminoids significantly decreased the viability/proliferation of lung cancer cells in a dose-dependent manner. However, total extract displayed the superior anticancer activity in the investigated cell lines. Crude extract in combination with cisplatin augmented the decrease in the viability of cancer cells compared with single compound treatment in A549 lung cancer cells. Total extract of Curcuma longa could be regarded as being more effective against lung cancer cells in vitro than its separated compounds.

Topics: A549 Cells; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Chemical Fractionation; Chromatography, High Pressure Liquid; Coumaric Acids; Curcuma; Curcumin; Diarylheptanoids; HT29 Cells; Humans; Mass Spectrometry; Neoplasms; Phytotherapy; Plant Extracts; Solvents

This paper aims to investigate the metabolism and pharmacokinetics of curcumin, demethoxycurcumin and bisdemethoxycurcumin in mice tumor. To improve water solubility, nanoparticle formulations were prepared as curcuminoids-loaded solid lipid nanoparticles (curcuminoids-SLNs) and curcumin-loaded solid lipid nanoparticles (curcumin-SLNs). After intragastric administration to tumor-bearing ICR mice, the plasma and tumor samples were analyzed by liquid chromatography with ion trap mass spectrometry. We discovered that curcuminoids were mainly present as glucuronides in plasma, whereas in free form in tumor tissue. A validated LC/MS/MS method was established to determine the three free curcuminoids in tumor homogenate. Samples were separated on a Zorbax SB-C(18) column, eluted with acetonitrile-water (containing 0.1% formic acid), and detected by TSQ Quantum triple quadrupole mass spectrometer in selected reaction monitoring mode. The method showed good linearity (r(2)=0.997-0.999) over wide dynamic ranges (2-6000 ng/mL). Variations within- and between-batch never exceeded 11.2% and 13.4%, respectively. The extraction recovery rates ranged from 78.3% to 87.7%. The pharmacokinetics of curcuminoids in mice tumor fit two-compartment model and first order elimination. For curcumin-SLNs group, the dosing of 250 mg/kg of curcumin resulted in AUC((0-48 h)) of 2285 ngh/mL and C(max) of 209 ng/mL. For curcuminoids-SLNs group, the dosing equivalent to 138 mg/kg of curcumin resulted in higher tumor concentrations (AUC=2811 ngh/mL, C(max)=285 ng/mL). It appeared that co-existing curcuminoids improved the bioavailability of curcumin.

Topics: Animals; Area Under Curve; Biphenyl Compounds; Chromatography, Liquid; Curcumin; Diarylheptanoids; Drug Delivery Systems; Drug Stability; Lignans; Linear Models; Lipids; Male; Mice; Mice, Inbred ICR; Nanoparticles; Neoplasm Transplantation; Neoplasms; Reproducibility of Results; Tandem Mass Spectrometry