Evaluation of antitumor property of extracts and steroidal alkaloids from the cultivated Bulbus Fritillariae ussuriensis and preliminary investigation of its mechanism of action

Abstract

BackgroundCancer is well known as a leading cause of death in the world. At present, it is the very active area to search for anticancer drugs from natural products. In this study, we evaluated the antitumor property of chloroform extract (CE), n-hexane extract (HE), water extract (WE) and steroidal alkaloids from the cultivated Bulbus Fritillariae ussuriensis (BFU) and its preliminary mechanism for its action was investigated.MethodsFirstly, cytotoxicity of the different extracts from BFU against Lewis lung carcinoma cell line (LLC), Human ovarian cancer cell line (A2780), human hepatocellular carcinoma cell line (HepG2), human lung carcinoma cell line (A549) was measured by MTT assay. Then, we identified the compounds from the active extract of BFU by bioassay guided isolation, determined their antitumor activity in vitro, and detected cell cycle distribution using flow cytometry. Moreover, the extract of BFU which showed remarked anti-proliferative activity in vitro was further evaluated using S180 and LLC tumor models. Additionally, a preliminary investigation of the mechanism of the action was carried out by using histological and immunohistochemical staining technique.ResultsThe results showed that CE and the purified total alkaloids of BFU (TAFU) exhibited stronger cytotoxic activity than the others (WE and HE). We further isolated the four main steroidal alkaloids from TAFU, and found all alkaloids showed significant cytotoxicity, and peimisine induced G0/G1 phase arrest and increased apoptosis. The results showed that TAFU had significant antitumor activity and low toxicity in vivo. Additionally, the immunohistochemical examinations signified that TAFU remarkably increased caspase-3 expression and reduced microvessel density (MVD) in tumor tissues of transplantable S180 and LLC tumor models.ConclusionsThese results achieved suggested that the steroidal alkaloids could hold a good potential for use as an antitumor drug. Notably, our finding is the first report on the antitumor activity of extracts and steroidal alkaloids from the cultivated BFU in vitro and in vivo and its mechanisms.

A Systematic Review on Traditional Uses, Sources, Phytochemistry, Pharmacology, Pharmacokinetics, and Toxicity of Fritillariae Cirrhosae Bulbus

“…Of course, some monomer chemical compositions have also been reported to exhibit advantageous effects on the treatment of endometrial cancer or ovarian cancer. A recent research suggested that peimisine (15 μ g/mL for 0–72 h) notably blocked the proliferation of human ovarian cancer cell through inducing apoptosis via increasing G0/G1 phase cell arrest [ 56 ].…”

Pharmacological Effects of Verticine: Current Status

“…This finding was consistent with that of Qi et al (2017) who proved the effect of verticine on cell viability, proliferation, and apoptosis of human leukemia and the function of reactive oxygen species and redox imbalance in this progress [ 10 , 11 ]. Some alkaloids could activate caspase-3 and caspase-dependent cell apoptosis [ 43 – 45 ], and stimulating the ROS production of K562 cell could promote caspase-3 expression and induce apoptosis [ 46 , 47 ]. Therefore, verticine might also activate caspase-3-related pathway in the process of stimulating ROS-induced apoptosis in K562/A02 cells.…”

Plant Resource Availability of Medicinal Fritillaria Species in Traditional Producing Regions in Qinghai-Tibet Plateau

“…It is believed that alkaloids are the major biological active constituents (Li et al, 2013 ; Wang et al, 2014a ). Recent pharmacological studies found that alkaloids from BFC exhibit remarkable antitussive, expectorant, anti-inflammatory effects (Wang et al, 2011 , 2012 ), antiasthmatic effect (Yan, 2005 ), hypotensive property (Kang et al, 2004 ), anti-bacterial activity (Li et al, 2005 ), and antitumor effect (Wang D. D. et al, 2014 ; Wang et al, 2014b , 2015 ).…”