Rabe, Shahrzad Taghizadeh
(Immunology Research Center, Bu-Ali Research Institute, School of Medicine, Mashhad University of Medical Science)
,
Emami, Seyed Ahmad
(Department of Pharmacognosy, Mashhad University of Medical Science)
,
Iranshahi, Mehrdad
(Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Science)
,
Rastin, Maryam
(Immunology Research Center, Bu-Ali Research Institute, School of Medicine, Mashhad University of Medical Science)
,
Tabasi, Nafise
(Immunology Research Center, Bu-Ali Research Institute, School of Medicine, Mashhad University of Medical Science)
,
Mahmoudi, Mahmoud
(Immunology Research Center, Bu-Ali Research Institute, School of Medicine, Mashhad University of Medical Science)
Background: Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate anti-cancer properties of this plant and elucidate potential underlying mec...
Background: Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate anti-cancer properties of this plant and elucidate potential underlying mechanisms for the effects. Materials and Methods: Anti-cancer potential was evaluated by toxicity against human melanoma and fibroblast cell lines. To explore the involved pathways, pattern of any cell death was determined using annexin-V/PI staining and also the expression of Bax and cytochrome c was investigated by Western blotting. Results: The results showed that SLAK selectively caused a concentration-related inhibition of proliferation of melanoma cells that was associated with remarkable increase in early events and over-expression of both Bax and cytochrome c. Conclusions: The current experiment indicates that Artemisia may have anti-cancer activity. We anticipate that the ingredients may be employed as therapeutic candidates for melanoma.
Background: Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate anti-cancer properties of this plant and elucidate potential underlying mechanisms for the effects. Materials and Methods: Anti-cancer potential was evaluated by toxicity against human melanoma and fibroblast cell lines. To explore the involved pathways, pattern of any cell death was determined using annexin-V/PI staining and also the expression of Bax and cytochrome c was investigated by Western blotting. Results: The results showed that SLAK selectively caused a concentration-related inhibition of proliferation of melanoma cells that was associated with remarkable increase in early events and over-expression of both Bax and cytochrome c. Conclusions: The current experiment indicates that Artemisia may have anti-cancer activity. We anticipate that the ingredients may be employed as therapeutic candidates for melanoma.
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제안 방법
The Herz-Högenauer technique was used to remove chlorophyll and phenolics (by lead (Π) acetate precipitation) and to prepare a crude sesquiterpene sample for further chromatographic/spectral investigation.
To better understand molecular events involved in any SLAK effect on apoptosis, effects of SLAK on Bax and cytochrome c expression-proteins pivotal for apoptosis - were analyzed. Figure 4 presents a representative Western blot from SLAK-treated (25-100µg/ml) and untreated cells.
To evaluate the anti-cancer potential of SLAK, proliferative responses of melanoma cell lines were assessed. SLAK dramatically inhibited the proliferation of four human melanoma cell lines (MM200, Mel-RM, Me4405 and A375), with Me4405 cells the most affected.
대상 데이터
Mousavi (Department of Pharmacology, Mashhad University of Medical Sciences, Mashhad, Iran). A375 cells (NCBI# C136) and human skin fibroblast-like HFFF2 cells (NCBI# C163) were purchased from the National Cell Bank of Iran (NCBI, Tehran). Origin and characteristics of these lines have been reported previously (Zhang et al.
데이터처리
The significance of differences was evaluated by one-way analysis of variance (ANOVA) and a Bonferroni’s post-hoc test using SPSS 11.0 software (Chicago, IL).
이론/모형
1% Nonidet (N) P-40, 10% glycerol, 1mM sodium vanadate, 1mM sodium fluoride, 1mM dithiothreitol (DTT), 1mM phenylmethylsulphonyl fluoride (PMSF) along with protease inhibitor cocktail (BioVision Inc, CA) for 45min on ice. The protein concentrations of cytosolic extracts were determined using Bradford assay. Equal amounts of protein (30-50μg/ml) of each cell lysate was dissolved in Laemmli’s sample buffer and subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE).
성능/효과
In conclusion, a sesquiterpene lactone fraction derived from the aerial portions of Artemisia khorassanica (SLAK) imparted considerable anti-cancer potential against human melanoma cell lines. For now, as these studies were all in vitro, it remains to be seen if the fraction might also impart anti-tumor activity in situ.
In each case, a minimum of 10,000 events was captured. Results were reported as percentages of Annexin V+ (early apoptosis), PI+ (necrosis), Annexin V+PI+ (double positive; late apoptosis), or Annexin V-PI-(double negative; non-staining) cells in each population analyzed.
To ascertain whether the SLAK-induced inhibition of melanoma cell survival was associated with induction of apoptosis, cell death patterns were evaluated. The results indicated the percentage of Annexin V+ cells (specifically, among Me4405 cells) was significantly increased by SLAK, indicating an increase in the incidence of apoptosis. Other studies have reported the cytotoxic effect of other sesquiterpene lactones in several cell lines occurred via apoptosis induction (Zhaia et al.
후속연구
This study also provides a basis for the potential use of SLAK as a component in any overall anti-cancer therapy. However, further investigations are required to elucidate the precise component responsible for the observed biological activities and effects in vivo need to also be evaluated so that the potential broader utility of the SLAK can be more precisely determined.
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