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The root of Croton crassifolius has been used as a traditional Chinese medicine (TCM), called Radix Croton Crassifolius, and commonly known as "Ji Gu Xiang" in Chinese. Its medicinal value has been recorded in several medical books or handbooks, such as "Sheng Cao Yao Xing Bei Yao", "Ben Cao Qiu Yuan" and "Zhong Hua Ben Cao". It has been traditional employed for treating sore throat, stomach-ache, rheumatism and cancer. At present, there are limited studies on the evaluation of low-polarity extracts of roots in C. crassifolius. Consequently, the aim of this study was to evaluate the antitumor effect of the low-polarity extract of C. crassifolius root. Extracts were obtained by supercritical fluid extraction. The extracts were tested for antitumor effects in vitro on several cancer cell lines. A CCK-8 kit was used for further analysis of cell viability. A flow cytometer and propidium iodide staining were used to evaluate the cell cycle and apoptosis. Hoechst staining, JC-1 staining and the fluorescence probe DCFH-DA were used to evaluate apoptotic cells. Molecular mechanisms of action were analyzed by quantitative RT‒PCR and Western blotting. Immunohistochemistry was used for the evaluation of xenograft tumors in male BALB/c mice. Finally, molecular docking was employed to predict the bond between the desired bioactive compound and molecular targets. Eleven diterpenoids were isolated from low-polarity C. crassifolius root extracts. Among the compounds, chettaphanin II showed the strongest activity (IC 50 = 8.58 μM) against A549 cells. Evaluation of cell viability and the cell cycle showed that Chettaphanin II reduced A549 cell proliferation and induced G2/M-phase arrest. Chttaphanin II significantly induced apoptosis in A549 cells, which was related to the level of apoptosis-related proteins. The growth of tumor tissue was significantly inhibited by chettaphanin II in experiments performed on naked mice. The antitumor mechanism of chettaphanin II is that it can obstruct the mTOR/PI3K/Akt signaling pathway in A549 cells. Molecular docking established that chettaphanin II could bind to the active sites of Bcl-2 and Bax. Taken together, the natural diterpenoid chettaphanin II was identified as the major antitumor active component, and its potential for developing anticancer therapies was demonstrated for the first time by antiproliferation evaluation in vitro and in vivo. [Display omitted] • Eleven diterpenoids were obtained from the SFE extract of C. crassifolius roots. • Chettaphanin II showed the strongest antitumor activity against A549 cells. • Chettaphanin II inhibited A549 cell proliferation and arrested cells in G2/M-phase. • Chettaphanin II induced A549 cell apoptosis by inhibiting PI3K/AKT/mTOR pathway. • Chettaphanin II significantly inhibited the growth of tumor tissue in nude mice. [ABSTRACT FROM AUTHOR]

Five diarylpentanol derivatives including two new compounds stellerasme A (1), stellerasme B (2) were isolated from the aerial parts ofStelleropsis tianschanica. Their structures were elucidated by various spectroscopic techniques (UV, IR, MS, CD, 1D and 2D NMR). All compounds were evaluated for their cytotoxicity activity against HeLa and KB cell lines, and compound1showed selective activities against HeLa cell line with an IC50value of 7.4 μM. [ABSTRACT FROM PUBLISHER]

[Display omitted] • Three new cadinene-type sesquiterpene dimers, named hibisceusones A-C, were isolated from H. tiliaceus. • Dimeric skeletons were formed from a unique 1,4-dioxane ring for the first time in natural products. • Compound 2 exhibited promising anti-TNBC activities by inducing the apoptosis of MDA-MB-231 cells by inhibiting the PI3Kα pathway. Three new cadinane-type sesquiterpenoid dimeric diastereomers (1 – 3) named hibisceusones A-C were obtained from the infected stems of Hibiscus tiliaceus. The structures were determined by NMR spectroscopy and MS techniques, and the absolute configurations were assigned by ECD and single-crystal X-ray diffraction techniques. Compounds 1 – 3 are diastereomers, and contain a 1,4-dioxane ring linearly fused to different cadinane-type polycyclic skeletons. This is the first time that such a structure has been identified in natural products. Compounds 1 – 3 exhibited cytotoxic activities, and 2 showed a significantly high anti-triple-negative breast cancer (TNBC) effect. The anti-cancer effect of compound 2 was 3–4 fold higher than that of 1 and 3. The anti-cancer effect was generated via the induction of the apoptosis of the MDA-MB-231 cells by inhibiting the PI3Kα pathway. [ABSTRACT FROM AUTHOR]

Plant-derived natural products have been the highly significant sources of novel antitumor agents. The cassane-type diterpenes of genusCaesalpiniahave been reported to bear antiproliferative activities toward different types of cancer cells. In this study, we evaluated the antineoplasmic activities of 16 natural origin cassane-type diterpenes isolated from the CHCl3extract of the seeds ofC. minaxin pituitary adenomas cells and identified caesalpin G (CAG) showed the strongest cytotoxicity. Moreover, we further investigated the structure–activity relationship and molecular mechanism of these derivatives systematically. The results confirmed the unsaturated lactone-type ring, hydroxyl at C-7, and alkenyl at C-11 or C-14 functionality as critical for anticancer activity in this family of natural products. In addition, the mechanism experiments also demonstrated unfolded protein response and ER stress and Wnt/β-catenin pathway were involved in the CAG-induced apoptosis. [ABSTRACT FROM PUBLISHER]

[Display omitted] • Fan@EM-HGB were designed and prepared using spontaneous emulsification and ionic cross-linking. • The released behavior of Fan@EM-HGB followed a pH-controlled mechanism. • Fan@EM-HGB promote the apoptosis of A549 cells in vitro. • Fan@EM-HGB inhibit the PI3K/Akt/mTOR signaling pathway in nude mice. • Emulsions-filled hydrogel beads could be considered as a potential carrier to delivery hydrophobic active composition. Fangchinoline (Fan) is a natural alkaloids compound with a series of remarkable bioactivity, but the poor aqueous solubility limits the clinical application. Emulsions (EM) systems are commonly used to encapsulate and deliver hydrophobic active compound to enhance the bioavailability. Hydrogel beads (HGB) are three-dimensional hydrophilic polymer networks, which are able to immobilize colloidal delivery systems, resulting to the enhanced stability and controlled release in the gastrointestinal tract. In order to give full play to the bilateral advantages of emulsion and hydrogel, Fan loaded EM-filled sodium alginate HGB (Fan@EM-HGB) were designed and prepared in this paper. The average size of Fan@EM was 121.6 ± 2.7 nm and the zeta potential was -17.7 ± 0.3 mV. Physicochemical characterization demonstrated that Fan was successfully encapsulated in HGB with entrapment efficiency of 93.98 % and drug loading of 5.18 mg/g. The released behavior of Fan@EM-HGB followed a pH-controlled mechanism that was consistent with the first-order model. In vitro activity research shown that Fan@EM-HGB could significantly promote the apoptosis of A549 cells, with IC 50 value more than 2.37 times higher than that of Fan. The in vivo results indicated that Fan@EM-HGB had an obvious anti- cancer effect, and molecular mechanism shown that Fan@EM-HGB could promote tumor cell apoptosis by inhibiting the activation of the PI3K/Akt/mTOR signaling pathway. The above research results suggest that nanoemulsions-filled hydrogel beads have potential application in delivery system for hydrophobic composition. [ABSTRACT FROM AUTHOR]

A new bis-γ-pyrone polypropionate compound onchidione II (1), together with three known compounds, was isolated from a marine pulmonate mollusc Onchidium struma, collected at Hainan Island of China. The structure of new compound was determined by extensive spectroscopic analyses including IR, 1D and 2D NMR techniques, and chemical methods. Compounds 1–4 were evaluated for their cytotoxicity against human tumor cell lines HepG-2, A549, and MCF-2. The results showed that compounds 1 and 2 were moderate cytotoxic against HepG-2, A549, and MCF-2 cell lines, with IC50 values from 13.2 to 22.4 μM. [ABSTRACT FROM AUTHOR]

Phytochemical investigation on the stems of Schisandra glaucescens resulted into the isolation of three new lanostane triterpenoids, 12-hydroxyschiglausin B (1), 12-hydroxykadsuphilactone B (2), and 20R-hydroxyschinalactone C (3). Structural elucidation of all the compounds was accomplished by spectral methods. The isolated compounds were tested in vitro for cytotoxic activities. As a result, triterpenoids 1 and 2 showed cytotoxic activities for all six tested tumor cell lines with IC50 values less than 15 μM. [ABSTRACT FROM AUTHOR]

Well-defined pH-responsive poly( ε-caprolactone)-graft- β-cyclodextrin-graft-poly(2-(dimethylamino)ethylmethacrylate)- co-poly(ethylene glycol) methacrylate amphiphilic copolymers (PCL- g- β-CD- g-P(DMAEMA- co-PEGMA)) were synthesized using a combination of atom transfer radical polymerization (ATRP), ring opening polymerization (ROP) and 'click' chemistry. Successful synthesis of polymers was confirmed by Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (H-NMR), and gel permeation chromatography (GPC). Then, the polymers could selfassemble into micelles in aqueous solution, which was demonstrated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The pH-responsive self-assembly behavior of these copolymers in water was investigated at different pH values of 7.4 and 5.0 for controlled doxorubicin (DOX) release, and these results revealed that the release rate of DOX could be effectively controlled by altering the pH, and the release of drug loading efficiency (DLE) was up to 88% ( W/ W). CCK-8 assays showed that the copolymers had low toxicity and possessed good biodegradability and biocompatibility, whereas the DOX-loaded micelles remained with high cytotoxicity for HeLa cells. Moreover, confocal laser scanning microscopy (CLSM) images revealed that polymeric micelles could actively target the tumor site and the efficient intracellular DOX release from polymeric micelles toward the tumor cells further confirmed the anti-tumor effect. The DOX-loaded micelles could easily enter the cells and produce the desired pharmacological action and minimize the side effect of free DOX. These results successfully indicated that pH-responsive polymeric micelles could be potential hydrophobic drug delivery carriers for cancer targeting therapy with sustained release. [ABSTRACT FROM AUTHOR]

Two new steroidal glycosides ponasteroside C (1) and ponasteroside D (2) were isolated from the aerial parts ofLepidogrammitis drymoglossoides. Their structures were elucidated by various spectroscopic techniques (IR, HRESIMS, 1D and 2D NMR). All compounds were evaluated for their cytotoxicity against HeLa and HCT-8 cell lines, and compounds1and2showed mild activity against all the test cell lines. [ABSTRACT FROM PUBLISHER]

Three novel furanoditerpenoids, norcaesalpinin J ( 1 ) featuring an unusual 20-norcassane hydroperoxide and phangininoxys B ( 2 ) and C ( 3 ) possessing cassane hemiketal skeletons, were isolated from the seeds of Caesalpinia sappan . Their structures were elucidated by extensive spectroscopic methods. All isolates were evaluated for the cytotoxic activities on three human cancer cell lines. [ABSTRACT FROM AUTHOR]

Abstract: Two novel diterpenes, norcaesalpinin I (1) featuring an unusual ring C-contracted dinorcassane and caesalpinin U (2) possessing a highly oxygenated furanocassane skeleton were isolated from the seeds of Caesalpinia minax. Their structures were determined by different spectroscopic methods. A plausible biosynthetic pathway of 1 was proposed. The cytotoxic activity of compounds 1 and 2 against HepG2 and HeLa human tumor cell lines was evaluated. [Copyright &y& Elsevier]

Abstract: Four novel diterpenes possessing rare five-membered peroxide ring, aphanaperoxides E–H (1–4), were isolated from stem bark of Aphanamixis polystachya. Their structures including the absolute configuration were elucidated by spectroscopic data and CD analysis. The cytotoxicities of the isolated compounds against a panel of human cancer cell lines were evaluated. [Copyright &y& Elsevier]

Two letters to the editor are presented in response to the article "Dose-Dense Paclitaxel Once a Week in Combination With Carboplatin Every 3 Weeks for Advanced Ovarian Cancer: A Phase 3, Open-Label, Randomised Controlled Trial," by N. Katsumata et al in the October 17, 2009 issue, along with the author's reply to the letters.