bisdemethoxycurcumin 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

Curcuminoids are turmeric-extracted phytochemicals with documented chemopreventive and anti-tumor activities against several types of malignancies. Curcuminoids can modulate several molecular pathways and cellular targets involved in different stages of tumor initiation, growth, and metastasis. Bisdemethoxycurcumin (BDMC) is a minor constituent (approximately 3%) of curcuminoids that has been shown to be more stable than the other two main curcuminoids, that is, curcumin and demthoxycurcumin. Recent studies have revealed that BDMC has anti-tumor effects exerted through a multimechanistic mode of action involving inhibition of cell proliferation, invasion and migration, metastasis and tumour growth, and induction of apoptotic death in cancer cells. The present review discusses the findings on the anti-tumor effects of BDMC, underlying mechanisms, and the relevance of finding for translational studies in human.

Topics: Animals; Antineoplastic Agents, Phytogenic; Curcumin; Diarylheptanoids; Humans; Neoplasms; Phytotherapy; Plants, Medicinal

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

Topics: Coated Materials, Biocompatible; Curcumin; Cytotoxins; Diarylheptanoids; Drug Carriers; Hep G2 Cells; Humans; Lactic Acid; Nanoparticles; Neoplasms; Polyglycolic Acid; Polylactic Acid-Polyglycolic Acid Copolymer

Curcumin, a natural compound extracted from the rhizomes of Curcuma Longa, is known to display pronounced anticancer activity but lacks good pharmacokinetic properties. In that respect, augmenting the water solubility by structural modification of the curcumin scaffold may result in improved bioavailability and pharmacokinetics. A possible scaffold modification, especially important for this study, concerns the imination of the labile β-diketone moiety in curcumin. Previous work revealed that novel N-alkyl β-enaminones showed a similar water solubility as compared to curcumin, accompanied by a stronger anti-proliferative activity. To extend this β-enaminone compound library, new analogues were prepared in this work using more polar amines (hydroxyalkylamines and methoxyalkylamines instead of alkylamines) with the main purpose to improve the water solubility without compromising the biological activity of the resulting curcuminoids. Compared to their respective parent compounds, i.e. curcumin and bisdemethoxycurcumin, the bisdemethoxycurcumin N-(hydroxy/methoxy)alkyl enaminone analogues showed better water solubility, antioxidant and anti-proliferative activities. In addition, the curcumin enaminones displayed activities comparable to or better than curcumin, and the water solubility was improved significantly. The constructed new analogues may thus be of interest for further exploration concerning their impact on oxidative stress related diseases such as cancer.

Topics: Amines; Antineoplastic Agents; Antioxidants; Cell Line, Tumor; Cell Proliferation; Curcuma; Curcumin; Diarylheptanoids; Humans; Neoplasms; Solubility; Water

In our ongoing search for new anti-invasive chemotypes, we have made an excursion from previously reported potent 1,3-diarylpropenones (chalcones) to congeners bearing longer linkers between the aromatic moieties. Nine 1,ω-diarylalkenones, including curcumin and bisdemethoxycurcumin, were evaluated in the chick heart invasion assay. Unfortunately, these compounds proved less potent and more toxic than earlier evaluated chemotypes. In the 1,3-diarylpenta-2,4-dien-1-one series, fluoro and/or trimethoxy substitution caused an increase in potency. This agrees with observations made earlier for the chalcone class.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Chalcones; Chickens; Curcumin; Halogenation; Heart; Humans; Neoplasm Invasiveness; Neoplasms; Structure-Activity Relationship

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