nsc-106399 and Carcinoma--Ehrlich-Tumor

Chromatographic investigation of fruits obtained from Citrullus colocynthis, growing in Saudi Arabia, led to isolation of two compounds; Cucurbitacin E glucoside (Cu E, 1), and Cucurbitacin I glucoside (Cu I, 2). The chemical structures of 1 and 2, were elucidated by spectroscopic analyses include; 1D ((1)H and (13)C) and 2D (COSY, HMQC and HMBC) NMR and ESI-MS spectroscopy. The in vitro cytotoxic activity against hepatoma cell line (HepG2) and mice-bearing tumor of Ehrlich's ascites carcinoma (EAC) of the compounds were estimated. Both compounds had potent inhibitory activity on HepG2 with IC(50) 3.5 and 2.8 nmol/mL, respectively. In addition to these activities, the in vivo study employing EAC, showed the capability of both compounds to prolong the survival time, life span and normalize the biochemical parameters of the infected mice with EAC.

Topics: Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Carcinoma, Hepatocellular; Cell Proliferation; Chromatography, Thin Layer; Citrullus; Cucurbitacins; Dose-Response Relationship, Drug; Fruit; Hep G2 Cells; Humans; Inhibitory Concentration 50; Liver Neoplasms; Magnetic Resonance Spectroscopy; Male; Mice; Molecular Structure; Plants, Medicinal; Saudi Arabia; Spectrometry, Mass, Electrospray Ionization; Time Factors; Triterpenes

We screened various food components for their ability to inhibit doxorubicin (DOX) permeability in tumor cells in vitro with the aim of finding novel modulators. Capsaicin did not change DOX permeability in the tumor cells, although the capsaicin derivatives gingerol and ferulic acid tended to promote DOX efflux. Combinations of these components with DOX were also not effective. In contrast, cucurbitacin E significantly promoted DOX influx into tumor cells and increased DOX concentration in tumor cells. Furthermore, combined cucurbitacin E significantly suppressed DOX efflux from tumor cells and was shown to maintain the DOX level in tumor cells. It was also confirmed that the combination of cucurbitacin E with DOX resulted in effective cytotoxicity for tumor cells in culture. Additionally, the combination of cucurbitacin E and DOX showed increased cytotoxicity when compared to each treatment alone. In vivo, DOX alone treatment did not change the time course of tumor size or tumor weight of M5076 ovarian sarcoma, compared to control levels. In contrast, the combination of cucurbitacin E with DOX resulted in decreased tumor size and tumor weight, compared to that in DOX alone group, indicating effective antitumor activity. In conclusion, the combination of cucurbitacin E with DOX may be an effective tool with treated application in the cancer chemotherapy.

Topics: Animals; Antibiotics, Antineoplastic; Biological Transport; Capsaicin; Carcinoma, Ehrlich Tumor; Catechols; Cell Line, Tumor; Coumaric Acids; Doxorubicin; Drug Screening Assays, Antitumor; Drug Synergism; Fatty Alcohols; Female; Male; Mice; Neoplasm Transplantation; Ovarian Neoplasms; Permeability; Sarcoma; Triterpenes