Cucurbitane-Type Triterpenoids from the Stems of <i>Cucumis melo</i>

Phytochemical investigation of the stems of Cucumis melo led to the isolation and identification of 21 cucurbitane-type triterpenoids, including nine new compounds (1−9) and 12 known compounds. Their structures were determined on the basis of spectroscopic analyses, chemical methods, and comparison with spectroscopic data in the literature. Two known compounds, cucurbitacin B (10) and cucurbitacin A (11), showed significant cytotoxic activity against the proliferation of A549/ATCC and BEL7402 cells in vitro. Of the new compounds, only compound 7 was weakly cytotoxic. The inhibitory effects of all compounds on the Jak-Stat3 signaling pathway were evaluated, but only cucurbitacin B (10) showed significant inhibitory activity of phosphotyrosine STAT3

Zardaverine dose- and time-dependently induces apoptosis.

<p><b>A</b>, Bel-7402 and SMMC-7721 cells were incubated with zardaverine for 48 h. <b>B</b>, Bel-7402 and SMMC-7721 cells were exposed respectively to 1 and 0.3 µM zardaverine for different periods. <b>C</b>, SNU-739 and HCT 116 cells were treated with 10 µM zardaverine for 72 h and 0.1 µM paclitaxel for 48 h. Whole-cell lysates were prepared and analyzed for cleavage of PARP, caspase-3, caspase-8, and caspase-9 by Western blotting.</p

The selective antitumor activity of zardaverine is independent of PDE3/4 inhibition.

<p><b>A,</b> Cells were incubated with 0.1, 1 and 10 µM zardaverine or vehicle for 1 h in the presence of 0.5 µM forskolin and intracellular cAMP levels were determined by a competitive immunoassay based on TR-FRET. RcP (relative cAMP production) was calculated from three independent experiments. <b>B,</b> Cells were incubated with different agents or vehicle for 24 h and intracellular cAMP levels were determined as noted in (<b>A</b>). Intracellular cAMP concentrations per 10⁶ cells (pM/10⁶ cells) were presented from three independent experiments. <b>C,</b> Cell proliferation inhibition effect of single or combined treatment with trequinsin and rolipram was determined by SRB assay. Proliferation inhibition rate of agents was compared to that of zardaverine in Bel-7402, SMMC-7721, SNU-739 and HCT 116 cells as shown in the histogram. <b>D</b>, Mice bearing human Bel-7402 and HCT 116 xenografts were orally administered zardaverine (200 mg/kg) or vehicle daily for 7 days, and cAMP levels of tumors at 3 h after the last administration were determined. cAMP concentration of tumors (pM/g ) was calculated as shown in the histogram. n  = 3 in both vehicle and treatment groups. Columns, means; bars, SEMs (n = 3; *p<0.05, **p<0.01).</p

Zardaverine inhibits the growth of human tumor xenografts <i>in vivo</i>.

<p>A, Mice bearing human HCC Bel-7402 xenografts were orally administered zardaverine or vehicle daily for 14 days. <b>B,</b> Mice bearing human colon cancer cell HCT 116 xenografts were orally administered zardaverine or vehicle daily for 21 days and intraperitoneally administered CPT-11 every 4 days for three times. Tumor volume was measured on the indicated days. n  = 10 in vehicle group and n  =  6 in treatment groups.</p

Zardaverine causes G₀/G₁ phase cell cycle arrest of sensitive cells.

<p><b>A,</b> Bel-7402, SMMC-7721, Bel-7404 and QGY-7701 cells were treated with 0.1 µM zardaverine or vehicle for 24 h, then collected, stained with PI, and analyzed by flow cytometry. Representative flow histograms depicting cell cycle distribution are shown from three independent experiments with similar results. <b>—</b>, vehicle; , 0.1 µM zardaverine. <b>B,</b> The histograms from (<b>A</b>) were analyzed by the ModFit LT program, and the percentage of cells in each phase of the cell cycle is shown. <b>C,</b> SNU-739 and HCT 116 cells were treated with 1 and 10 µM zardaverine or vehicle for 24 h, then determined and analyzed as described above. Data shown in (<b>B</b>) and (<b>C</b>) are mean ± SEM from three independent experiments.</p

Antitumor activity of zardaverine <i>in vitro</i>.

<p>Cells seeded in 96-well plates were treated with various concentrations of agents for 72 h and cell viability was determined by SRB assay. IC₅₀ values represent the concentrations required to inhibit cell growth by 50%. All SRB data are presented as mean ± SEM from three independent experiments.</p

The selective antitumor activity of zardaverine is closely related to the regulation of cell cycle-associated proteins.

<p>Bel-7402 and SMMC-7721 cells (A), SNU-739 and HCT 116 cells (B) were incubated with zardaverine for 24 h. Then whole-cell lysates were prepared and analyzed by Western blotting. C, Cells were seeded in 6-well plates overnight. Whole-cell lysates were prepared, then total Rb levels were determined by Western blotting. IC₅₀ values of zardaverine for these cells listed here are from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0090627#pone-0090627-t001" target="_blank">Table 1</a>.</p

A Novel Water-Soluble Heptaplatin Analogue with Improved Antitumor Activity and Reduced Toxicity

A novel water-soluble heptaplatin analogue, cis-[(4R,5R)-4,5-bis-(aminomethyl)-2-isopropyl-1,3-dioxolane](3-hydroxy-1,1-cyclobutanedicarboxylato)platinum(II), has been synthesized and biologically evaluated. The complex shows more activity and less toxicity than its parent drug heptaplatin, exhibiting the great potential for further development

A Novel Water-Soluble Heptaplatin Analogue with Improved Antitumor Activity and Reduced Toxicity

A novel water-soluble heptaplatin analogue, cis-[(4R,5R)-4,5-bis-(aminomethyl)-2-isopropyl-1,3-dioxolane](3-hydroxy-1,1-cyclobutanedicarboxylato)platinum(II), has been synthesized and biologically evaluated. The complex shows more activity and less toxicity than its parent drug heptaplatin, exhibiting the great potential for further development

Unusual Dimeric Chemical Structure for a Carboplatin Analogue as a Potential Anticancer Complex

An unexpected and unusual dimeric platinum(II) tetracarboxylate complex was obtained by the reaction of cis-[Pt(NH3)2I2] with disilver dicarboxylate. The complex exhibits greater in vitro anticancer activity and lower toxicity in mice than its parent compound, carboplatin, and is therefore worthy of further evaluation as a potential antitumor dinuclear platinum agent