The in Vitro and in Vivo Antitumor Activities of Tetracyclic Triterpenoids Compounds Actein and 26-Deoxyactein Isolated from Rhizome of Cimicifuga foetida L
| Autor: | Chen Qing, Xiaodong Hu, Ming-Hua Qiu, Desong Wu, Yajuan Chen, Qi Yao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Cimicifuga Cell cycle checkpoint Lung Neoplasms actein Pharmaceutical Science IC50 Pharmacology Plant Roots Analytical Chemistry Mice 0302 clinical medicine Drug Discovery Sarcoma 180 Mice Inbred ICR medicine.diagnostic_test Cell cycle Chemistry (miscellaneous) 030220 oncology & carcinogenesis Molecular Medicine cell cycle Cell Survival 26-deoxyactein antitumor activity Mice Nude HL-60 Cells Biology Article Flow cytometry 03 medical and health sciences In vivo medicine Animals Humans Physical and Theoretical Chemistry Cell Proliferation A549 cell Dose-Response Relationship Drug Organic Chemistry Saponins Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays In vitro Triterpenes 030104 developmental biology Cell culture A549 Cells Rhizome |
| Zdroj: | Molecules; Volume 21; Issue 8; Pages: 1001 Molecules |
| ISSN: | 1420-3049 |
| DOI: | 10.3390/molecules21081001 |
| Popis: | Aims: This work aims to study the in vitro and in vivo antitumor activities of tetracyclic triterpenoids compounds actein and 26-deoxyactein. Further, the mechanism is investigated. Methods: In vitro, a modified MTT method was used to assay the cytotoxicities of actein and 26-deoxyactein in 12 human tumor cell lines. In vivo, mouse sarcoma S180 and human lung cancer A549 cells were respectively implanted subcutaneously in ICR mice and nude mice to establish implanted tumor models. Flow cytometry (FCM) was used to assay the cycle distribution of the tumor cells. Immunohistochemistry was used to measure CD31-positive expression in the xenogrft tumor by analyzing microvessel density (MVD). In addition, acute toxicities of actein and 26-deoxyactein were also evaluated. Results: Actein and 26-deoxyactein inhibited the proliferation of the 12 human cancer cell lines tested with the values of 50% inhibitory concentrations (IC50) between 12.29 and 88.39 μg/mL. In vivo, both actein (3–27 mg/kg) and 26-deoxyactein (3–27 mg/kg) significantly inhibited the growth of the implanted sarcoma S180 in a dose-dependent manner. Actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) markedly inhibited the xenograft growth with T/C (%) values of 38%, 55% for actein, and 35%, 49% for 26-deoxyactein. Compared with the vehicle control, actein (10, 30 mg/kg) and 26-deoxyactein (10, 30 mg/kg) significantly reduced the MVD in the xenograft tumor. The FCM result showed that human leukemia HL-60 cells were arrested at G1 phase after treated with either actein (6.25–25 μg/mL) or 26-deoxyactein (6.25–25 μg/mL) for 48 h. A limited trial in mice showed that both of the minimal lethal doses (MLDs) of actein and 26-deoxyactein were over 5 g/kg. Conclusions: Both actein and 26-deoxyactein have low toxicities. Importantly, both these two tetracyclic triterpenoids compounds isolated from rhizome of Cimicifuga foetida L. have significant antitumor activities in vitro and in vivo, which is associated with cell cycle arrest and angiogenesis inhibition. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|