Synergistic Growth Inhibitory Effects of Eryngium kotschyi Extracts with Conventional Cytotoxic Agents: Cisplatin and Doxorubicin against Human Endometrium Cancer Cells.

BACKGROUND: Endometrial cancer is one of the most common types of cancer. For this reason, various studies have been carried out on its treatment and the effects of natural products on this disease. OBJECTIVES: This study aimed to examine the growth inhibitory effects of Eryngium kotschyi Boiss. ethyl acetate [EKE] and butanol [EKB] obtained from the main methanol [EKM] extract from the aerial parts on human endometrium carcinoma [RL95-2] cells and their synergistic effect with cisplatin or doxorubicin. METHODS: RL95-2 cells were treated with E. kotschyi extracts either alone or in combination with cisplatin or doxorubicin. The effects on cell growth were determined using the MTT assay and real-time cell analysis xCELLigence. RESULTS: The extracts demonstrated growth inhibitory activity, with a certain degree of selectivity against the RL95-2 cell line. Synergistic effects of EKE/cisplatin or doxorubicin at different concentration levels were demonstrated in RL95-2 cells. In some instances, the EKE/doxorubicin combinations resulted in antagonistic effects. The reduction level of cell viability was different and specific to each combination for the RL95-2 cell line. CONCLUSION: The growth inhibitory activity of cisplatin or doxorubicin, as a single agent, may be modified by combinations of the extracts and be synergistically enhanced in some cases. A significant synergistic effect of EKE on the RL95-2 cell line with cisplatin and doxorubicin was observed. This cytotoxic effect can be investigated in terms of molecular mechanisms. This study is the first of its kind in the literature. The mechanisms involved in this interaction between chemotherapeutic drugs and plant extracts remain unclear and should be further evaluated.

Cytotoxic evaluation and LC-MS/MS analysis of aerial parts of Eryngium kotschyi Boiss. grown in Turkey

Abstract Increasing biological activity and phytochemical investigations on Eryngium species showed its potential as pharmaceutical approach. Eryngium kotschyi Boiss. is one of the species of Eryngium genus and is endemic to Turkey. It is known that this plant is traditionally used in the South-western part of Turkey for the treatment of various diseases. This study focuses on cytotoxic activities of methanol extract and ethyl acetate, n-butanol and water sub-extracts from E. kotschyi in A549, COLO 205 and MDA-MB-231 cell lines by Sulforhodamin B assay and qualitative and quantitative determination of phytochemical constituents in active extract by LC-MS/MS. From the result of the study, it was seen that E. kotschyi ethyl acetate (EKE) sub-extract showed the strongest cytotoxic effect with the low IC50 values (50.00; 31.96 and 22.26 µg/mL in A549; COLO 205 and MDA-MB-231 cells at 48 h, respectively). Preliminary examination of the mass spectrums revealed the presence of 15 phytochemical compounds in active sub-extract and 7 of them was quantified. According to quantitative analyses the main compounds of EKE sub-extract were rosmarinic acid (485.603 µg/mgextract), chlorogenic acid (62.355 µg/mgextract) and caffeic acid (59.266 µg/mgextract). Moreover, this preliminary study on inhibitory activity of EKE sub-extract suggests further toxicologic investigations and detailed investigation on cytotoxic effect of various combinations of determined compounds

Triterpene saponins from Eryngium kotschyi.

Four new oleanane-type saponins 3-O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucuronopyranosyl-22-O-ß,ß-dimethylacryloylA1-barrigenol (1), 3-O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucuronopyranosyl-22-O-angeloylA1-barrigenol (2), 3-O-ß-D-glucopyranosyl-(1 → 2)-[ß-D-glucopyranosyl-(1 → 6)]-ß-D-glucopyranosyl-21,22,28-O-triacetyl-(3ß,21ß,22α)-olean-12-en-16-one (3), and 3-O-ß-D-glucopyranosyl-(1 → 2)-glucopyranosyl-22-O-ß-D-glucopyranosylsteganogenin (4), along with the known 3-O-ß-D-galactopyranosyl-(1 → 2)-[α-L-arabinopyranosyl-(1 → 3)]-ß-D-glucuronopyranosyl-22-O-angeloylA1-barrigenol and 3-O-α-L-rhamnopyranosyl-(1 → 4)-ß-D-glucuronopyranosyloleanolic acid, were isolated from a methanol extract of the roots of Eryngium kotschyi by multiple chromatographic steps. Saponins 3 and 4 are unusual by the original structure of their aglycon. Compound 3 possessed an oleanane-type skeleton with a 21,22,28-triacetylation and a ketone function at the C-16 position. For compound 4, the 17,22-seco-oleanolic acid skeleton is rarely found in natural saponins.