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.
Highlights
Cancer is well known as a leading cause of death in the world
We identified the compounds from the active extract of Bulbus Fritillariae ussuriensis (BFU) by bioassay guided isolation, and determined their antitumor property in vitro
Four steroidal alkaloids were obtained from total alkaloids of BFU (TAFU) and identified as imperialine (I), peimisine (II), verticinone (III), and verticine (IV) (Figure 1) based on their physical and spectral data which showed good agreement with published references [9,11,12]
Summary
Cancer 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. Bulbus Fritillariae ussuriensis (BFU) is the well-known food and folk medicine distributed in the Northeast Provinces of China, such as Liaoning, Heilongjiang and Jiling provinces, because it has remarkable antitussive, expectorant and antiasthmatic activities [1]. The previous studies have exhibited that the crude alkaloid extracts of BFU possess remarkable antitussive, expectorant and antiasthmatic activities [2,3]. In vitro previous studies suggested that verticinone, imperialine and peimisine from BFU inhibited angiotensin I converting enzyme activity in a dose-dependent manner [4], and in vivo ethylacetate and butanol extracts from BFU significantly lowered the mean arterial pressure, decreased angiotensin converting enzyme and angiotensin I-induced vasoconstriction, and they increased nitric oxide (NO) and cGMP productions in intact vascular tissue [5]. Imperialine, chuanbeinone, verticinone, verticine, imperialine-βN-oxide, isoverticine and isoverticine-β-N-oxide isolated from genus Fritillaria have significant anti-inflammatory effect in vivo [8,9]
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