Xerophilusin B induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma cells and does not cause toxicity in nude mice.[Pubmed: 25555195]

Esophageal cancer is the eighth most common cancer in the world and ranks as the sixth leading cause of cancer-related mortality. Esophageal cancer has a poor prognosis partially due to its low sensitivity to chemotherapy agents, and the development of new therapeutic agents is urgently needed. Here, the antitumor activity of a natural ent-kaurane diterpenoid, xerophilusin B (1), which was isolated from Isodon xerophilus, a perennial herb frequently used in Chinese folk medicine for tumor treatment, was investigated. Compound 1 exhibited antiproliferative effects against esophageal squamous cell carcinoma (ESCC) cell lines in a time- and dose-dependent manner with lower toxicity against normal human and murine cell lines. In vivo studies demonstrated that 1 inhibited tumor growth of a human esophageal tumor xenograft in BALB/c nude mice without significant secondary adverse effects, indicating its safety in treating ESCC. Furthermore, 1 induced G2/M cell cycle arrest and promoted apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway in ESCC cell lines. In conclusion, the observations herein reported showed that 1 is a potential chemotherapeutic agent for ESCC and merits further preclinical and clinical investigation for cancer drug development.

ent-Abietane diterpenoids from Isodon xerophilus.[Pubmed: 21725806]

Three new ent-abietanoids, named xerophilusins XIV-XVI, and four known analogues, as well as four known chemical constituents were isolated from the leaves of Isodon xerophilus. Their structures were elucidated by extensive spectroscopic studies, and comparison with literature data. In addition, the cytotoxic activity of the ent-abietanoids against chronic myelogenous leukemia (K562), stomach adenocarcinoma (MKN45), and hepatocellular carcinoma (HepG2) human cell lines was investigated and no activities were observed.

Cytotoxic ent-kauranoids from the medicinal plant Isodon xerophilus.[Pubmed: 17665952]

Bioassay-directed fractionation of the leaves of the medicinal plant Isodon xerophilus led to the isolation of a series of potential antitumor molecules. Thirteen new (1-13) and 23 (14-36) known diterpenoids were isolated and identified, representing ent-kauranoids of several structural types. The structures of 1-13 were determined by means of spectroscopic studies. The absolute configurations of the new compounds were clarified by CD spectroscopic studies or were postulated on biogenetic grounds. All compounds obtained were evaluated for their cytotoxic activity against the K562, MKN45, and HepG2 cell lines. Compounds 1, 2, 11, 16-19, 23, 26-28, 30, and 32 demonstrated significant cytotoxic activity for one or more cell lines.

Isolation of two bioactive ent-kauranoids from the leaves of Isodon xerophilus.[Pubmed: 17595108]

Isodon xerophilus has been used as a herbal cold tea for the prevention and treatment of sore throat and inflammation in southernwestern China. A phytochemical study on the ethyl acetate (EtOAc) soluble fraction of I. xerophilus leaves led to the isolation of two new ent-kauranoids, xerophinoids A (1) and B (2), together with 14 known diterpenoids. The structures of xerophinoids A (1) and B (2) were illustrated using spectroscopic methods including 1D and 2D NMR analyses. To study their biological activities, the effects of xerophinoids A (1) and B (2) on nitrite production, tumor necrosis factor (TNF)-alpha and interleukin (IL)-1beta were examined. In addition, xerophinoids A (1) and B (2) also exhibited potent cytotoxicity against several human tumor cell lines (IC50 < 11 microM), but they had no toxicity on human T-lymphocyte (C8166).

ent-Kaurane diterpenoids from the leaves of Isodon xerophilus.[Pubmed: 12391566]

From the ethanolic extract of the leaves of Isodon xerophilus, three new ent-kaurane diterpenoids named xerophilusins L-N (1 - 3), together with three known ones designated as rabdoternin A (4), longikaurin F (5) and ponicidin (6), were isolated and structurally elucidated. Compound 6 demonstrated most potent cytotoxic activity against K562 and T24 human tumor cell lines with IC(50) = 0.09 and 0.32 microg/ml, respectively.

Cytotoxic 7,20-epoxy ent-kauranoids from Isodon xerophilus.[Pubmed: 11524129]

Four 7,20-epoxy ent-kaurane diterpenoids, xerophilusins G (1) and I-K (2-4), were isolated from the leaves of Isodon xerophilus, along with four known ones, enanderianin C (5), rosthorin A (6), longikaurin B (7), and rabdoternin D (8). Their structures were determined primarily using NMR spectroscopic techniques. The structure and stereochemistry of 3 were confirmed by X-ray crystallography. Compounds 4 and 7 exhibited broad cytotoxicity against four kinds of human tumor cells (K562, HL-60, HCT, and MKN-28 cells) in the range of 2.23-15.35 and 0.30-8.61 microg/ml, respectively.

New 7,20:14,20-diepoxy ent-kauranoids from Isodon xerophilus.[Pubmed: 10843567]

Three new 7,20:14,20-diepoxy-ent-kaurane diterpenoids, xerophilusins A-C (1-3), together with a known one, macrocalin B (4), were isolated from the leaves of Isodon xerophilus. Their structures were elucidated on the basis of their spectral properties and X-ray crystallographic analysis. Compounds 1, 2, and 4 showed significant cytotoxic activity against K562, HL-60, and MKN-28 cells.