Pleumchitt Rojanapanthu

Damnacanthal, a noni component, exhibits antitumorigenic activity in human colorectal cancer cells

Damnacanthal, an anthraquinone compound, is isolated from the roots of Morinda citrifolia L. (noni), which has been used for traditional therapy in several chronic diseases including cancer. Although noni has been consumed for a long time in Asian and Polynesian countries, the molecular mechanisms by which it exerts several benefits are starting to emerge. In this report, we examined systematic approaches on the cancer-suppressing capability of damnacanthal in colorectal tumorigenesis. Damnacanthal exhibits cell growth arrest as well as caspase activity induction in colorectal cancer cells. We also examined several potential target proteins and found that the proapoptotic protein nonsteroidal anti-inflammatory activated gene-1 (NAG-1) is highly induced. Subsequently, we have found that damnacanthal also enhances transcription factor CCAAT/enhancer binding protein β (C/EBPβ), which controls NAG-1 transcriptional activity. Blocking of C/EBPβ by shRNA results in the reduction of NAG-1 expression as well as caspase activity in the presence of damnacanthal. Taken together, these results indicate that damnacanthal increases antitumorigenic activity in human colorectal cancer cells and that C/EBPβ plays a role in damnacanthal-induced NAG-1 expression.

Damnacanthal-induced anti-inflammation is associated with inhibition of NF-κB activity.

Morinda citrifolia L. (Rubiaceae), commonly called noni, is a traditional folk medicinal plant with a long history of use for several diseases. Its anti-inflammation activity has been proposed, but detailed knowledge of this antiinflammation mechanism remains unclear. Here, we investigated the effects of noni extract and its major bioactive component damnacanthal on anti-inflammation in vivo as well as in vitro. Our data demonstrate that noni extract and its bioactive component damnacanthal exhibit suppression of inflammation as evidenced by the suppression of paw and ear edema in rats and mice, and down-regulation of lipopolysaccharide-induced nuclear factor-κB (NF-κB) activity, respectively. As a result, the expression of pro-cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were suppressed in the presence of damnacanthal. These results provide a potential use of damnacanthal in the treatment of inflammatory-related diseases.

Physicochemical Properties of Amphotericin B Liposomes Prepared by Reverse-Phase Evaporation Method

Abstract The physicochemical properties of phosphatidylcholine-cholesterol liposomes containing amphotericin B and prepared by reverse-phase evaporation method were studied. Uniformly dispersed liposomal suspensions were obtained by employing 3:1 ratio (by volume) of diethyl ether to normal saline, 5 min sonication time at 7°C, and evaporation of diethyl ether at 25°C. Microscopic examination showed that the prepared liposomes were spheroids with unilamellar, oligolamellar, or multilamellar structure. The liposomes containing amphotericin B 2.0 mol% of total lipid led to the highest percentage of drug entrapment. Liposomes with maximum entrapment efficiency were obtained from using 250 µmol of total lipid. The liposomal amphotericin B possessing the highest drug entrapment efficiency (approximately 95%) with particle size range of 1307–1451 nm was the one composed of 1:1 molar ratio of phosphatidylcholine to cholesterol.

Self-assembled nanomicelles of damnacanthal-loaded amphiphilic modified chitosan: Preparation, characterization and cytotoxicity study

Damnacanthal (Dam) is a phytochemical with many pharmacological properties including anticancer activity. However, its hydrophobicity, poor bioavailability and stability limit its application in many biological approaches. In this study, Dam nanomicelles as an emerging platform were developed to overcome limitations. The deoxycholic and poly(ethylene glycol) methyl ether grafted chitosan (DCA-CS-mPEG) was synthesized and characterized by FTIR and 1H NMR and the degree of substitution (DS) was determined by elemental analysis (EA). This polymer formed self-assembled micelles with a core-shell structure and a critical micelle concentration (CMC) of 37.2μg/mL. Dam-loaded polymeric micelles were prepared by dialysis method and characterized by DLS, TEM, FTIR, DSC and HPLC. The mean particle size of Dam-loaded micelles was about 200nm with spherical shape. The drug entrapment efficiency was up to 57.7%. FTIR and DSC analysis revealed that Dam was entrapped in the micelles in the amorphous state. The in vitro release profiles of Dam from micelles were sustained release and pH-sensitive behavior. Cytotoxic studies exhibited the comparable efficacy and safety of this delivery system. Overall these results indicate the possible utilization of DCA-CS-mPEG micelles as a promising carrier for hydrophobic compounds like Dam.

Damnacanthal and its nanoformulation exhibit anti-cancer activity via cyclin D1 down-regulation.

AIMS Damnacanthal is an anthraquinone isolated from the root of Morinda citrifolia L. (noni), and it exhibits many pharmacological properties, including anti-cancer activity. Damnacanthal targets several signal transduction proteins related to cell growth inhibition or apoptosis. However, the molecular mechanisms by which damnacanthal affects cell cycle regulation have not been elucidated in detail. MAIN METHODS Cyclin D1 is an important regulatory protein in cell cycle progression and is overexpressed in many cancer cells. In this study, we investigated the molecular mechanism of damnacanthal on cyclin D1 expression. KEY FINDINGS We found that damnacanthal inhibited growth of several cancer cell lines (HCT-116, HT-29, MCF-7 and PC-3) in a dose- and time-dependent manner with a decrease in cyclin D1 protein expression. Damnacanthal did not change mRNA of cyclin D1; rather it suppressed cyclin D1 expression at the post-translational level. Subsequent experiments with several mutant cyclin D1 constructs suggest that the lysine sites of cyclin D1 play a pivotal role in damnacanthal-mediated cyclin D1 degradation. Furthermore, damnacanthal was encapsulated in self-assembled chitosan nanoparticles to improve both physicochemical and biological activities. SIGNIFICANCE Our results suggest that encapsulated damnacanthal exhibits better activity in cell growth inhibition, compared to non-encapsulated damnacanthal. Thus, damnacanthal has potential to be a candidate for the development of chemoprevention or therapeutic agents for cancers.

Chitosan‑based nanoparticles with damnacanthal suppress CRM1 expression

Cancer is one of the leading causes of mortality worldwide. Phytochemicals may be promising anticancer agents given their various chemical structures and diverse biological activities. Damnacanthal (DAM) is a major bioactive component of Noni, which has been investigated previously as a cancer-preventive or chemotherapeutic agent. DAM has also been reported to exhibit anti-proliferative activity in several cancer types. In the present study, it was identified that DAM downregulates chromosome maintenance protein 1 (CRM1) expression in human cancer cells. The application of chitosan-based nanoparticles (NPs) with DAM also induced CRM1 downregulation, which suggests that chitosan-based NPs may be effective vehicles for delivery of phytochemicals such as DAM. It was also identified that DAM increased the levels of the tumor suppressor non-steroidal anti-inflammatory drugs-activated gene 1 in the nucleus, thereby leading to enhanced anticancer effects. The results of the present study indicate that DAM and its nanoformulation may be a candidate anticancer drug.

Abstract 2625A: Damnacanthal and its nanoformulation suppress cyclin D1 expression

Damnacanthal is an anthraquinone isolated from the root of Morinda citrifolia L. (Noni) and exhibits many pharmacological properties including anti-cancer activity. It has been reported that Damnacanthal targets several signal transduction proteins related to cell growth inhibition or apoptosis. However, the molecular mechanisms by which Damnacanthal affects anti-cancer activity has not been elucidated in details. Cyclin D1 is the important regulatory protein in cell cycle progression and overexpressed in many cancer cells. In this study, we investigated the molecular mechanism of damnacanthal on cyclin D1 expression. We found that damnacanthal inhibited growth of several cancer cells (HCT-116, HT-29, MCF-7 and PC-3) in a dose- and time- dependent manner with decreasing in cyclinD1 protein expression. Damnacanthal did not change mRNA of cyclin D1, rather it suppressed cyclin D1 expression at the post-translational level. Subsequent experiments with dominant negative mutant cyclin D1 suggest that cyclin D1 at the lysine sites plays a pivotal role in damnacanthal-mediated cyclin D1 suppression. Furthermore, damnacanthal was encapsulated in self-assembled chitosan nanoparticle to improve both physicochemical and biological activities. Our results suggest that encapsulated damnacanthal exhibits better activity in cell growth inhibition, compared to non-encapsulated damnacanthal. Damnacanthal nanoformulation has potential to be a candidate for development of chemoprevention or therapeutic agent for cancers. Grant support: This work was supported by grant from the University of Tennessee Center of Excellence in Livestock Diseases and Human Health and The Thailand Research Fund (TRF) and Faculty of Pharmacy, Mahidol University (IRG5780007). Citation Format: Pakin Sukamporn, Pleumchitt Rojanapanthu, Seung Joon Baek. Damnacanthal and its nanoformulation suppress cyclin D1 expression. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2625A.

The Efficacy of Subgingivally Delivered Andrographis Paniculata Gel to Treat Patients with Periodontitis

This study compared the clinical effects of scaling and root planing (SRP) after the adjunctive subgingival administration of Andrographis paniculata (AP) gel or placebo (PB) gel in a 6-month clinical trial for patients with chronic periodontitis. The study was a split-mouth, single-blind, randomiz ed, controlled clinical trial that compared two treatment modalities (SRP+PB and SRP+AP) in single-rooted teeth with a probing depth (PD) of 5 mm or more. The clinical parameters, including PD, clinical attachment level (CAL), plaque index (PI), gingival index (GI), bleeding on probing (BOP), and radiographic examinations, were recorded at baseline, 3 months, and 6 months. The results showed that both treatmen t groups significantly improved with regard to clinical parameters ( p 0.05), although SRP+AP showed a greater PD reduction than SRP+PB ( p<0.05) between baseline and 3 months. In conclusion, the adjunctive use of AP gel significantly reduces PD a nd significantly improves attachment level.