| In vitro: |
| Planta Med. 2010 Jan;76(1):82-5. | | Antiproliferative and apoptotic activities of linear furocoumarins from Notopterygium incisum on cancer cell lines.[Pubmed: 19653148] | Bioassay-guided fractionation of the antiproliferative chloroform extract of the traditional Chinese medicine Qiang-Huo (Notopterygium incisum) led to the isolation of nine linear furocoumarins (1- 9).
METHODS AND RESULTS:
All the isolates were tested against two human cancer cell lines (HepG-2 and MCF-7) and a rat cancer cell line (C6) using the MTT assay method. Among them, notopol (1), notopterol (2), 5-[(2 E,5 Z)-7-hydroxy-3,7-dimethyl-2,5-octadienoxy]psoralene (3), and 5-[(2,5)-epoxy-3-hydroxy-3,7-dimethyl-6-octenoxy]psoralene (4) showed significant antiproliferative activity against the HepG-2 and C6 cancer cell lines, with IC(50) values of 7.7-24.8 microg/mL (5-FU: ca. 5 microg/mL). Compounds 1- 3 also showed moderate cytotoxicity against the MCF-7 cancer cell line, with IC(50) values of 39.4-61.3 microg/mL (5-FU: 17.3 microg/mL). The cell cycle-specific inhibition and apoptosis induced by compounds 1 and 2 were determined using flow cytometry.
CONCLUSIONS:
The structure-activity relationship (SAR) is briefly discussed herein. It was found that the presence of a free hydroxy at the lipophilic side chain linked to C-5 of the linear furocoumarins was essential for their in vitro antiproliferative activity. |
|
| In vivo: |
| Chem Pharm Bull (Tokyo). 1993 May;41(5):926-9. | | Analgesic component of Notopterygium incisum Ting.[Pubmed: 8339339] |
METHODS AND RESULTS:
Notopterol was identified as the analgesic component of Notopterygium incisum TING by using the acetic acid-induced writhing method. Notopterol also indicated an anti-inflammatory activity by its inhibitory effect in the vascular permeability test. The intensive prolongation of pentobarbital-induced hypnosis was possibly caused by its inhibitory effect on the drug metabolism in liver. Pharmacological differences between the analgesic components of N. incisum, Aralia cordata and Angelica pubescens were also discussed. | | Drug Des Devel Ther . 2019 Jun 6;13:1927-1940. | | Notopterol-induced apoptosis and differentiation in human acute myeloid leukemia HL-60 cells[Pubmed: 31239643] | | Abstract
Purpose: This study aims to observe the effects of notopterol on the apoptosis and differentiation of HL-60 cells and to explore the underlying molecular mechanisms. Methods: Cell viability was assessed using sulforhodamine B assay. Cell proliferation was determined by the trypan blue dye exclusion test. Colony-forming units were assayed in methylcellulose. Apoptosis assays were carried out by annexin V-fluorescein isothiocyanate(FITC)/propidium iodide (PI) double staining, Hoechst 33342 staining, mitochondrial membrane potential, and Western blot. Wright-Giemsa staining, nitroblue tetrazolium (NBT) reduction assay, CD11b and CD14 and Western blot were detected for induction of differentiation. In addition, cell-cycle phase distribution was analyzed by flow cytometry and Western blot. The combination therapy of notopterol and all-trans retinoic acid (ATRA) on HL-60 cells was examined. Results: Notopterol obviously inhibited the growth of HL-60 cells with an IC50 value of 40.32 μM and remarkably reduced the number of colonies by 10, 20, and 40 μM. In addtion, notopterol induced the percentage of apoptotic HL-60 cells, reduced the mitochondrial membrane potential, decreased the protein expresstion of Bcl-2 and Mcl-1, and increased the expression of Bax, cleavage of caspase 9, caspase 3, and PARP. As for cell differentiation, notopterol clearly induced chromatin condensation; increased the nucleocytoplasmic ratio, nitroblue tetrazolium-positive cells, expression of CD14 and CD11b, and protein expression of c-Jun and Jun B, and decreased c-myc. Furthermore, notopterol induced the G0/G1 cell-cycle arrest as determined using flow cytometry, which may be related to the regulation of cell-cycle-related proteins p53, CDK2, CDK4, Cyclin D1, Cyclin E, and survivin. The combined use of notopterol and ATRA did not enhance the apoptotic effect as evidenced by cell viability test and Hoechst 33342. However, the combination of notopterol and ATRA enhanced the effect of inducing differentiation when compared with using either notopterol or ATRA alone, which can be evidenced by the increased nucleocytoplasmic ratio, NBT positive cells, and expression of CD14. Conclusion: This is the first time it has been demonstrated that notopterol could induce apoptosis, differentiation, and G0/G1 arrest in human AML HL-60 cells, suggesting that notopterol has potential therapeutic effects on AML. The combination application of notopterol (20 and 40 μM) and ATRA (2 μM) could augment differentiation of HL-60 cells.
Keywords: AML; apoptosis; cell growth; cycle arrest; differetiation; notopterol. |
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