Isolation of anticancer constituents from Cucumis prophetarum var. prophetarum through bioassay-guided fractionation.

BACKGROUND: Cucumis prophetarum var. prophetarum is used in Saudi folk medicine for treating liver disorders and grows widely between Abha and Khamis Mushait City, Saudi Arabia. METHODS: Bioassay-guided fractionation and purification were used to isolate the main active constituents of Cucumis prophetarum var. prophetarum fruits. These compounds were structurally elucidated using NMR spectroscopy, mass spectral analyses and x-ray crystallography. All fractions, sub-fractions and pure compounds were screened for their anticancer activity against six cancer cell lines. RESULTS: The greatest cytotoxic activity was found to be in the ethyl acetate fraction, resulting in the isolation of five cucurbitacin compounds [E, B, D, F-25 acetate and Hexanorcucurbitacin D]. Among the cucurbitacins that were isolated and tested cucurbitacin B and E showed potent cytotoxicity activities against all six human cancer cell lines. CONCLUSION: Human breast cancer cell lines were found to be the most sensitive to cucurbitacins. Preliminary structure activity relationship (SAR) for cytotoxic activity of Cucurbitacins against human breast cancer cell line MDA-MB-231 has been reported.

Biocatalysis of the anticancer sipholane triterpenoids.

The Red Sea sponge Callyspongia (= Siphonochalina) siphonella is a rich source of sipholane triterpenoids. Biocatalysis of the major sipholanes, sipholenol A (1) and sipholenone A (2), respectively, by Mucor ramannianus ATCC 9628 and Cunninghamella elegans ATCC 7929 afforded four new metabolites 3 - 6 along with sipholenol G and 28-hydroxysipholenol A. Major sipholanes along with their biocatalytic products were investigated for their antiproliferative activity against the highly malignant +SA mouse mammary epithelial cell line. Sipholenone A (2) was the most active sipholane inhibiting +SA cell proliferation with an IC(50) value of 20 - 30 microM. Sipholenone A, also, showed cytotoxicity against MCF-7 at a dose of 0.9 microM and antiangiogenic activity in the CAM (chorio-allantoic membrane) assay. This is the first report on anticancer activity of these triterpenoids.

Isolation and characterization of ribosome-inactivating proteins from Cucurbitaceae.

Due to their RNA-N-glycosidase activity, ribosome-inactivating proteins (RIPs) are attractive candidates as antitumor and antiviral agents in biomedical and agricultural research. We have isolated and characterized two such proteins, foetidissimin II and texanin, from two Cucurbitaceae species. Foetidissimin II, obtained from the roots of Cucurbita foetidissima, was identified as a type-2 RIP, with a molecular weight of 61 kDa, as estimated by gel electrophoresis. It is composed of two chains, a 29-kDa chain A, and a 32-kDa chain B. Texanin, isolated from the fruits of Cucurbita texana, is a type-I RIP, with a single chain of molecular weight 29.7 kDa, as estimated by MALDI-TOF-MS. Both proteins exhibit RNA-N-glycosidase activity, with aniline playing a critical role in rRNA cleavage. The IC50 value of foetidissimin II, determined by cell-free protein-synthesis inhibition, was 0.251 muM. In an in vitro cytotoxicity assay, foetidissimin II exhibited IC50 values of ca. 70 nM to both adenocarcinoma and erythroleukemia cells. Texanin exhibited a weaker anticancer activity against erythroleukemia cells, with an IC50 value of 95 microM, but no activity against adenocarcinoma cells. The N-terminal sequences of both proteins were compared with those of reported RIPs.

Proliferative activity of Echinacea angustifolia root extracts on cancer cells: Interference with doxorubicin cytotoxicity.

Doxorubicin is an anticancer drug that causes apoptosis in cells, but cardiotoxicity limits the cumulative dose that can remain in the blood. Echinacea extracts have been prescribed to supplement cancer chemotherapy. In a recent study, it was reported that Echinacea purpurea extracts protected noncancerous cells from apoptosis. Our study aimed to determine interference with doxorubicin chemotherapy, and if fractions and compounds from Echinacea angustifolia roots protected the cells. Cervical and breast cancer cells were treated with the Echinacea samples and doxorubicin. At 0.05 and 0.5 microM doxorubicin concentration, cynarine increased HeLa cell growth by 48-125% and 29-101%, respectively (p<0.01). At 0.05 microM doxorubicin concentration, chicoric acid increased cell growth by 23-100% (p<0.01). When MCF-7 cells were treated with Echinacea and doxorubicin, the ethyl acetate fraction increased cell growth by 20-25%, and chicoric acid increased cell growth by 10-15%. Cynarine showed proliferative activity on HeLa cells, but showed antiproliferative activity on MCF-7 cells. Results indicate that phenolic compounds are responsible for proliferative activity. Studies with individual compounds show that chicoric acid and cynarine interfered with cells treated with 0.5 microM doxorubicin. The results of this study show that Echinacea herbal medicines affect cell proliferation despite cancer treatment, and that herbal medicines require further study with respect to anticancer drugs.

Lignans from Schisandra hernyi with DNA cleaving activity and cytotoxic effect on leukemia and Hela cells in vitro.

The lignans, gomisin G (1), schisantherin A (2), benzoylgomisin Q (3) and isoanwulignan (4) were isolated from the stems of Schisandra henryi. Compound 1 showed moderate DNA strand scission activity and significant cytotoxic effect on leukemia and Hela cells in vitro. Compound 1 represents a new type of DNA strand scission agent.

Ananosic acids B and C, two new 18(13-->12)-abeo-lanostane triterpenoids from Kadsura ananosma.

Two new 18(13-->12)-abeo-lanostane triterpenoid acids, ananosic acids B (1) and C (2), were isolated from the stems of Kadsura anaosma. Their structures were elucidated by spectral studies and chemical transformation. Compounds 1 and 2 were evaluated for cytotoxicity using CCRF-CEM leukemia cells and HeLa cells.

Triterpenoids from Schisandra henryi with cytotoxic effect on leukemia and Hela cells in vitro.

Four known lanostane triterpenoids, schiprolactone A (1), schisanlactone B (2), nigranoic acid (3) and schisandronic acid (4) were isolated from the stems of Schisandra henryi for the first time. Their structures were characterized by IR, MS and NMR techniques. Compounds 1, 2 and 4 showed moderate cytotoxic activity against Leukemia cells in vitro. Cytotoxic activity of compounds 1-4 showed IC50 of 0.0097, 0.01, 0.097 and 0.0099 micromol/mL respectively toward Leukemia cells and IC50 of 0.097, 0.1, 0.097 and 0.099 micromol/mL toward Hela cells respectively. It is the first report that these compounds possess cytotoxic activity on Leukemia and Hela cells.

Copacamphane, picrotoxane, and alloaromadendrane sesquiterpene glycosides and phenolic glycosides from Dendrobium moniliforme.

Seven sesquiterpene glycosides with copacamphane, picrotoxane, and alloaromadendrane sesquiterpene aglyons along with three phenolic glycosides have been isolated from the stems of Dendrobium moniliforme. Among them, dendromonilisides A-D (1-4) were characterized as new compounds, and their structures were determined on the basis of spectral and chemical methods and by X-ray diffraction analysis. The six known compounds were identified as dendrosides A, C, and F, dendromoniliside E, vanilloloside, and acanthoside B. In a preliminary biological test procedure, compounds 1, 3, and vanilloloside were found to stimulate the proliferation of B cells and inhibit the proliferation of T cells in vitro.