ABSTRACT
Nervosine VII is one of the known saturated pyrrolizidine alkaloids isolated from the plant of Liparis nervosa. This is first study to investigate the antitumor activity of nervosine VII in vitro, and the results indicated that nervosine VII induced autophagy and apoptosis in HCT116 human colorectal cancer cells. Mechanistic studies showed that nervosine VII-induced apoptosis was associated with the intrinsic pathway by the activation of caspase-9, -3 and -7. Autophagy induced by nervosine VII was characteristic with the regulation of autophagic markers including the increase of LC3-II and beclin 1 proteins, and the decrease of p62 protein. Nervosine VII simultaneously induced autophagy and apoptosis by activated MAPKs signaling pathway including JNK, ERK1/2 and p38, suppressing the p53 signaling pathway.
Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Autophagy/drug effects , Plant Extracts/pharmacology , Pyrrolizidine Alkaloids/pharmacology , HCT116 Cells , Humans , Orchidaceae/chemistryABSTRACT
We isolated two new lathyrane-type diterpenes L27 (1) and L28 (2) along with seven known compounds (3-9) from the seeds of Euphorbia lathyris. These compounds were identified by NMR, high-resolution electrospray ionisation (HR-ESI)-MS as well as IR spectroscopy. Compounds 1 and 2 were assigned NMR spectrums with 1H-NMR, 13C-NMR, distortionless enhancement by polarization (DEPT), correlation spectroscopy (COSY), heteronuclear multiple quantum coherence (HMQC), heteronuclear multiple bond connectivity (HMBC) and nuclear Overhauser effect spectroscopy (NOESY). Stereo configuration of 1 and 2 were confirmed by comprehensive interpretation of their nuclear Overhauser effect (NOE) relationship and showed they were first natural lathyrane-type diterpenes possessing α-configuration substitutes at C-3. Cytotoxicity assay of isolated compounds were evaluated against breast cancer cell lines MCF-7 or MDA-MB-231, 786-0 and liver cancer cell lines HepG2. As a result, Euphorbia factor L28 (2) showed strongly cytotoxicity to the 786-0 and HepG2 cell lines, with an IC50 value of 9.43 and 13.22 µM, respectively, which preliminarily suggested that the configuration of lathyrane-type diterpene at C-3 has a significant effect on its bioactivity.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Diterpenes/pharmacology , Euphorbia/chemistry , Plant Extracts/pharmacology , Seeds/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Line, Tumor , Cell Proliferation/drug effects , Diterpenes/chemistry , Diterpenes/isolation & purification , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Hep G2 Cells , Humans , MCF-7 Cells , Molecular Conformation , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Structure-Activity RelationshipABSTRACT
AIM: To observe the curative effect of Weiansan (WAS) on gastric precancerous lesions (GPL) and H pylori elimination. METHODS: Seventy-six patients with GPL were randomly divided into two groups: WAS group (n = 42) and Weifuchun (WFC) group (n = 34). The patients in the WAS group were administered 5 g WAS 3 times a day, and the patients in the WFC group took WFC (4 tablets) 3 times a day. To monitor inflammation of gastric mucosa, degree of glandular atrophy (GA), intestinal metaplasia (IM) and dysplasia, and H pylori infection, all patients underwent gastroscopy and biopsy with pathological examination before and after treatment. Fifty male Sprague-Dawley (SD) rats were used in animal experiments. Of these, 10 served as the control group (n = 10), 40 were given ranitidine combined with N-methyl-N(1)-nitro-N-nitrosoguanidine (MNNG) for 12 wk and divided into 4 groups randomly: model group (n = 10), high-dose WAS group (n = 10), low-dose WAS group (n = 10) and WFC group (n = 10). Twelve weeks later, all rats were killed and a 2 cm multiply 1 cm tissue was taken from the lesser curvature of the gastric antrum. H pylori infection was determined by the fast urease method. RESULTS: The curative effect in WAS groups was similar to that in WFC groups. There was no statistical difference in degree of GA, IM and dysplasia between WAS and WFC groups. The rate of H pylori infection in the model group (positive/negative: 9/1) was significantly higher than that in the control group (positive/negative: 1/9) (P < 0.01). H pylori elimination in the high-dose WAS group (positive/negative: 4/6) and low-dose WAS group (positive/negative: 6/4) was similar to that in the WFC group (positive/negative: 4/6) (P > 0.05). CONCLUSION: WAS improves clinical symptoms by suppressing GA, IM and dysplasia and eliminating H pylori.
