Molecular mechanisms of Lycoris aurea agglutinin‐induced apoptosis and G2/M cell cycle arrest in human lung adenocarcinoma A549 cells, both in vitro and in vivo

Zeitschrift Für Naturforschung C

et al. 2015

Lectins, a group of highly diverse proteins of non-immune origin and are ubiquitously distributed in plants, animals and fungi, have multiple significant biological functions, such as anti-fungal, anti-viral and, most notably, anti-tumor activities. A lectin was purified from the rhizomes of Aspidistra elatior Blume, named A. elatior lectin (AEL). In vitro experiments showed that the minimum inhibitory concentrations of AEL against the vesicular stomatitis virus, Coxsackie virus B4, and respiratory syncytial virus were all the same at about 4 μg/mL. However, AEL was ineffective against the Sindbis virus and reovirus-1. AEL also showed significant in vitro antiproliferative activity towards Bre-04, Lu-04, HepG2, and Pro-01 tumor cell lines by increasing the proportion of their sub-G1 phase. However, AEL failed to restrict the proliferation of the HeLa cell line. Western blotting indicated that AEL induced the upregulation of cell cycle-related proteins p53 and p21. The molecular basis and species-specific effectiveness of the anti-proliferative and anti-viral potential of AEL are discussed.

Section: In Vitro Anti-proliferative Potential Of Ael On Human Tumor supporting

confidence: 93%

“…FACScan flow cytometry was performed as previously described [21]. The percentages of cells at different cell cycle phases, or those that were undergoing apoptosis, were evaluated using Calibur FACScan flow cytometry (Becton Dickinson, Franklin Lakes, NJ, USA).…”

Section: Cell Cycle Measurementmentioning

confidence: 99%

Antiviral and antitumor activities of the lectin extracted from Aspidistra elatior

Zhang

Zeitschrift Für Naturforschung C

et al. 2015

“…The degrees of antiproliferation against human carcinoma cell lines resulting from treatments were evaluated by the MTT assay, and the growth inhibitory rate was expressed as the percentage of the total cells compared with the negative control after 72 hours treatment. Studies showed that a number of Amaryllidaceae alkaloids and their derivatives exhibited remarkable antiproliferative activities89104145. Our results in Table 2 also displays that hippeastrine, [2] benzopyrano [3,4] indole skeleton based lycorenine-type alkaloids, exhibited distinct dose-dependent antiproliferative activities against HT-29 and Hep G2 cells with the IC 50 values at 3.98 ± 0.29 μg/mL and 11.85 ± 0.20 μg/mL, as compared to that of camptothecin at 1.47 ± 0.07 μg/mL and 3.17 ± 0.56 μg/mL, 5-FU at 2.92 ± 0.48 μg/mL, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…Owing to the diverse pharmacological activities, such as anticancer, antimalaria, antifungal, neuroprotective effects, acetylcholinesterase and butyrylcholinesterase-inhibitory activity4567, these alkaloids have attracted a great deal of attentions in modern medical societies. Furthermore, some AAs exhibited significant anticancer effects and were very promising in the treatment of various cancers8910.…”

mentioning

confidence: 99%

Antiproliferative activities of Amaryllidaceae alkaloids from Lycoris radiata targeting DNA topoisomerase I

Tian

et al. 2016

Sci Rep

Crude Amaryllidaceae alkaloids (AAs) extracted from Lycoris radiata are reported to exhibit significant anti-cancer activity. However, the specific alkaloids responsible for the pharmacodynamic activity and their targets still remain elusive. In this context, we strived to combine affinity ultrafiltration with topoisomerase I (Top I) as a target enzyme aiming to fish out specific bioactive AAs from Lycoris radiata. 11 AAs from Lycoris radiata were thus screened out, among which hippeastrine (peak 5) with the highest Enrichment factor (EF) against Top I exhibited good dose-dependent inhibition with IC50 at 7.25 ± 0.20 μg/mL comparable to camptothecin (positive control) at 6.72 ± 0.23 μg/mL. The molecular docking simulation further indicated the inhibitory mechanism between Top I and hippeastrine. The in vitro antiproliferation assays finally revealed that hippeastrine strongly inhibited the proliferation of HT-29 and Hep G2 cells in an intuitive dose-dependent manner with the IC50 values at 3.98 ± 0.29 μg/mL and 11.85 ± 0.20 μg/mL, respectively, and also induced significant cellular morphological changes, which further validated our screening method and the potent antineoplastic effects. Collectively, these results suggested that hippeastrine could be a very promising anticancer candidate for the therapy of cancer in the near future.

“…FACScan flow cytometry assays were performed as previously described [12] . The percentages of the cells at different cell cycle phases or those that were undergoing apoptosis were evaluated by Calibur FACScan flow cytometry (Becton Dickinson, Franklin Lakes, NJ, USA).…”

Section: Cell Culturementioning

confidence: 99%

Antitumor effects of concanavalin A and Sophora flavescens lectin in vitro and in vivo

Shi

et al. 2013

Acta Pharmacol Sin

Aim: Proteins with legume lectin domains are known to possess a wide range of biological functions. Here, the antitumor effects of two representative legume lectins, concanavalin A (ConA) and Sophora flavescens lectin (SFL), on human breast carcinoma cells were investigated in vitro and in vivo. Methods: Human breast carcinoma MCF-7 cells and human normal mammary epithelial MCF-10A cells were examined. Cell viability was detected using WST-1 and CCK-8 assays. Cell apoptosis was analyzed with Hoechst 33258 staining. Cell cycle was investigated using flow cytometry. The expression of relevant proteins was measured using Western blotting. Breast carcinoma MCF-7 bearing nude mice were used to study the antitumor effects in vivo. The mice were injected with ConA (40 mg/kg, ip) and SFL (55 mg/kg, ip) daily for 14 d. Results: ConA and SFL inhibited the growth of MCF-7 cells in dose-and time-dependent manners (IC 50 values were 15 and 20 μg/mL, respectively). Both ConA and SFL induced apoptotic morphology in MCF-7 cells without affecting MCF-10A cells. ConA and SFL dosedependently increased the sub-G 1 proportion in MCF-7 cells, while SFL also triggered the G 2 /M phase cell cycle arrest. Both ConA and SFL dose-dependently increased the activities of caspase-3 and caspase-9 and release of cytochrome c from mitochondria into cytoplasm, up-regulated Bax and Bid, and down-regulated Bcl-2 and Bcl-X L in MCF-7 cells. ConA reduced NF-κB, ERK, and JNK levels, and increased p53 and p21 levels, while SFL caused similar changes in NF-κB, ERK, p53, and p21 levels, but did not affect JNK expression. Administration of ConA and SFL significantly decreased the subcutaneous tumor mass volume and weight in MCF-7 bearing nude mice. Conclusion: ConA and SFL exert anti-tumor actions against human breast carcinoma MCF-7 cells both in vitro and in vivo.