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Gardening Help Search. Winter hardy to USDA Zones where it will thrive in average, moist but well-drained soils in full sun. Established plants tolerate drought. Birds and small mammals love the fruit and are primary agents of seed disbursal. Seed will also travel to new locations in moving water.
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Oncotarget a primarily oncology-focused, peer-reviewed, open access, biweekly journal aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science. Its scope is unique.
The term "oncotarget" encompasses all molecules, pathways, cellular functions, cell types, and even tissues that can be viewed as targets relevant to cancer as well as other diseases. The term was introduced in the inaugural Editorial , Introducing OncoTarget. Sponsored Conferences. Impact Journals is a member of the Society for Scholarly Publishing. Keywords: autophagy, autophagic cell death, vacuolization, colon cancer, zanthoxylum fruit. Zanthoxylum fruit, obtained from the Japanese pepper plant Zanthoxylum piperitum De Candolle , and its extract Zanthoxylum fruit extract, ZFE have multiple physiological activities e.
However, the potential anticancer activity of ZFE has not been fully examined. Based on morphology and expression of marker proteins, ZFE-induced cell death was neither apoptosis nor necrosis. Normal intestinal cells were not affected by ZFE. Taken together, our findings show that ZFE induces JNK-dependent ACD, which appears to be the main mechanism underlying its anticancer activity, suggesting a promising starting point for anticancer drug development.
Cancer is one of the leading causes of death worldwide, and global cancer rates are predicted to increase over the coming years. Chemotherapy is one of the major treatment methods for cancer. Natural products constitute a promising resource for drug development and have always played a key role in pharmaceutical research [ 1 ].
Moreover, many single compounds derived from herbs, as well as herbal extracts, have been used clinically to treat various diseases including cancer [ 2 ]. Zanthoxylum piperitum De Candolle ZPDC , a deciduous aromatic spiny shrub or small tree native to Japan, is of considerable commercial importance.
Zanthoxylum fruit obtained from ZPDC is also an important component of kampo, a form of Japanese traditional medicine [ 3 , 4 ]. Previous studies on ZPDC constituents have revealed they can prevent propagation of influenza virus [ 5 ], inhibit adipogenesis in an obese mouse model [ 6 ], induce vascular relaxation via endothelium-dependent NO-cGMP signaling [ 7 ], inhibit cholesterol acyltransferase activity [ 8 ], and act as potent tyrosinase inhibitors [ 9 ].
In contrast to its effects on other diseases, the anticancer activity of ZPDC has not been widely investigated. The anticancer effects of two different forms of Zanthoxylum have been cited in the literature. In addition, a phytoglycoprotein from Korean ZPDC was reported to inhibit hepatocarcinogenesis [ 11 ]. In this study, we tested the anticancer effect of Zanthoxylum fruit extract ZFE on four different types of human cancer cell lines colon, liver, lung, and breast and then investigated its molecular mechanism of action in the colorectal cancer cell line DLD We found that ZFE causes remarkable cytoplasmic vacuolization in certain types of human cancer cells, leading to the inhibition of cell proliferation and ultimately inducing autophagic cell death ACD.
First, we investigated the effect of ZFE on the morphology of cancer cells using phase-contrast microscopy. To determine the effect of ZFE on the proliferation of cancer cells, we performed cell proliferation assays. Therefore, we investigated the mechanism of the anticancer effect of ZFE in more detail in the human colorectal cancer cell line DLD Figure 1: ZFE induces vacuolization and inhibits proliferation in some cancer cells.
Effect of ZFE on the morphology of the indicated cells. Error bars represent S. Cell viability was calculated as the percentage of cells excluding Trypan blue. DOX treatment for 24 h was used as a positive control for caspase activation.
The occurrence of vacuoles induced by treatment with ZFE was confirmed by electron microscopy Figure 2a. Electron-microscopic examination of DLD-1 cells after 24 h treatment with ZFE revealed abundant vacuoles and double-membrane structures sequestering cellular organelles, i. Arrows indicate autophagosomes center. Arrowheads indicate autolysosomes right. Cell lysates were prepared and subjected to Western blotting with the indicated antibodies.
Similar results were obtained in three independent experiments. Ctrl; control. Autophagy can be inhibited by knocking down the expression of essential autophagy-related genes ATG. Non-transfected DLD-1 cells were used as control. Non-transfected DLD-1 cells were used as controls. Twenty-four hours after transfection, cell lysates were subjected to Western blotting with the indicated antibodies. Cell viability was measured using a cell proliferation assay kit. Furthermore, the reduction in proliferation following treatment with ZFE was significantly attenuated by JNK inhibitor treatment Figure 4d.
Cells were treated with 0. DLD-1 cells were treated with the indicated reagents for 6 h. ZFE had no effect on any of these features. Figure 5a and 5b and Supplementary Figure S3b. In this study, we found that ZFE induces numerous autophagy-like cytoplasmic vacuoles, inhibits cell proliferation, and induces cell death in certain human cancer cell lines. Autophagy is an intracellular degradation system that delivers cytoplasmic constituents to the lysosome [ 12 , 13 ].
As such, autophagy plays an important role in the clearance of long-lived proteins and damaged organelles, such as mitochondria, as well as the removal of intracellular pathogens [ 14 ]. Cancer cells are likely to be more dependent on autophagy than normal cells [ 15 ].
Indeed, basal autophagy activity is elevated in the hypoxic regions of tumors [ 16 ]. Cancer cells subjected to stress e. In some circumstances, excessive activation of autophagy can lead to cell death. ACD, which refers to cell death caused by supraphysiological levels of autophagy, is accompanied by extensive autophagic vacuolization of the cytoplasm and a characteristic vacuolated appearance [ 18 ].
It has been proposed that ACD should be regarded as a modality of non-apoptotic and non-necrotic programmed cell death, in which autophagy serves as the mechanism of cell death.
ACD is morphologically defined especially by transmission electron microscopy as cell death that occurs in the absence of apoptosis i. With this morphological definition in mind, we observed that cancer cells treated with ZFE exhibited an increase in autophagic flux. This observation was confirmed by increased expression of autophagic markers i.
Moreover, the level of LC3-II relative to actin is correlated with the number of autophagosomes per cell [ 21 ]. Therefore, ZFE-induced cell death resembled ACD, as determined by morphology and the level of a key autophagic marker. The autophagy-related gene 5 ATG5 -ATG12 complex, a key regulator of the early autophagic pathway, is required for the formation of autophagosomes. We demonstrated that ZFE-induced cancer cell death and autophagic vacuolization were clearly suppressed by ATG5 knockdown.
However, the precise mechanism underlying ACD is still unclear, and the link between autophagy and cell death remains to be elucidated. Induction of high levels of autophagy may provide a valuable therapeutic strategy for treating cancer. The prospect of establishing novel cancer treatments by modulating autophagy has improved in recent years. Natural compounds such as resveratrol and curcumin have been implicated in the induction of ACD in various cancer cell lines in vitro [ 24 — 26 ]. The findings in these reports are compatible with the observations reported in this study.
The JNK pathway is involved in regulating autophagy of cancer cells in response to various stressors i.
By contrast, ZFE did not exert these effects in normal intestinal cells or other types of cancer cells i. The JNK pathway is also involved in the induction of apoptosis [ 35 ]. However, our results did not support the involvement of apoptosis in ZFE-induced cell death. This observation agreed closely with previous results reported by Shimizu et al. Further studies are needed to explore the molecular details of this process.
We also attempted to identify the active component s of ZFE. However, no such anticancer activity could be detected for either compound, in contrast to the results obtained using ZFE Supplementary Figure S4.
Further studies are needed to identify the active anticancer component s of ZFE. In summary, we showed that ZFE induces vacuolization and inhibits proliferation of human colorectal and liver cancer cells. Taken together, our findings provide novel evidence suggesting that ZFE is a useful tool for analyzing ACD in cancer cells.
Moreover, ZFE represents be a promising resource for anticancer drug development. Osaka, Japan. Preparation of Zanthoxylum fruit extract powder, provided by Tsumura Tokyo, Japan , is described briefly according to Tsumura. The soluble extract was then separated from the insoluble waste and concentrated by removal of water under reduced pressure. Spray drying was used to generate a dried extract powder.
The cells were gently scraped from the dishes and pelleted in a microcentrifuge. Pelleted cells were then dehydrated with a graded series of ethanol and finally embedded in EponThe ultra-thin sections were cut with an ultramicrotome, contrasted with saturated aqueous solutions of uranyl acetate and lead citrate, and examined using a transmission electron microscope H; Hitachi High Technologies, Tokyo, Japan.
Subsequently, the cells were treated with 0. Cells were then harvested, and Trypan blue was added to the cell suspension to a final concentration of 0. Cell viability was defined as the percentage of live cells i. Luminescence from blank wells medium without cells was subtracted.
Data were normalized against the luminescence of control cells. Ten microliters of each sample was loaded onto aTwenty-four hours after transfection, protein and total RNA was extracted. All data represent results from at least three independent experiments. The authors wish to acknowledge A Sugitani, Center for Clinical and Biomedical Research, Sapporo Higashi-Tokushukai Hospital, for his help in interpreting the statistical analysis of this study.
The re-emergence of natural products for drug discovery in the genomics era.
Normal black peppercorns need more heat than you'll get in Britain — but there are extraordinary alternatives which will spice up your cooking and even save you a fortune, as Mark Diacono explains. There are a few things that will indicate when I succumb too fully to middle age: not kicking a windfall apple that happens to have fallen in my path, not having to have chocolate and ice cream when I go to the cinema — and not bending down, as I walk past the pepper plants that grow in my garden, to rub their leaves. For eight months of the year, their spice scent perfumes my fingertips — and long may it continue. The black pepper that sits on most kitchen tables comes from a plant that is native to southern India and requires heat beyond the capability of these islands, but we can grow other kinds of pepper.
Fruits: Bright red, slightly fleshy, one-seeded, globose drupes" (Henderson, ). Habitat/ecology: "Brazilian pepper tree is an aggressive pioneer species.
Guns n Roses is one of the most popular rock music bands in America. Hundreds of famous lyricists have used the names of various popular plants and flowers in their famous poems and plays. Shakespeare has also used fragrant rich flowers name in his famous plays such as Hamlet and Romeo and Juliet. There are lots of video games related to plants and trees which are captivating the hearts of players.
It has a slight lemony flavour but often you may not be able to tell, you are more likely to recognize it as a herb.
For the latest on RHS Shows in , read more. Make a donation. This plant will provide nectar and pollen for bees and the many other types of pollinating insects. It is included in an evolving list of plants carefully researched and chosen by RHS experts. Divided into 3 groups these lists, linked below, are maintained by a team of RHS staff and are reviewed annually.
Zanthoxylum piperitum L. If you have any useful information about this plant, please leave a comment. Comments have to be approved before they are shown here. If you would like to support this site, please consider Donating. Home Search Contact. Vol 1 - 4 and Supplement. Publication Author Bean. English translation Publication Author Ohwi.
The bark and fruit are also aromatic. Sprays of small, yellow-green flowers are produced in early summer, followed by tiny, red fruit that split open to.
Shapes Green when young turning to bright red as they matures Taste Slightly bitter Health benefits Beneficial for colds, hypertension, depression, irregular heartbeat, menstrual disorders, urinary tract infections Brazilian Pepper tree Schinus terebinthifolia , also known as aroeira, rose pepper, broadleaved pepper tree, wilelaiki, Christmasberry, and Florida Holly, Brazilian holly, Brazilian pepper, Brazilian pepper tree, broad leaf pepper tree, broad-leaved pepper tree, Christmas berry, Christmas berry tree, Japanese pepper, pepperina, schinus and South American pepper , is a sprawling shrub or small tree in the sumac family, Anacardiaceae, which also includes poison ivy, poison oak, poison sumac and poisonwood. The plant is native to subtropical and tropical South America southeastern Brazil, northern Argentina, and Paraguay. Even so, Schinus molle or the Peruvian Pepper, a close relative of the Brazilian Pepper, is the source of the pink peppercorns that you sometimes see in gourmet pepper mills.
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This is an evergreen tree to 6 metres tall and is common in older suburbs where it was sometimes used as a street tree.
It focuses on the attributes of plants suitable for food forests, what each can contribute to a food forest ecosystem, including carbon sequestration, and the kinds of foods they yield. The book suggests that community and small-scale food forests can provide a real alternative to intensive industrialised agriculture, and help to combat the many inter-related environmental crises that threaten the very future of life on Earth. A deciduous shrub growing to about 15 feet, preferring a loamy soil but not really fussy as to soil or location. The ground-up seeds are used as a pepper substitute whilst the bark and leaves are used as a spice. The pulverized berries are the standard spice for sprinkling on broiled eel kabayaki-unagi and is one of the main ingredients of the blended spice called shichimi. A good forest garden plant.
In Florida it grows on range of moist to mesic sites, in pinelands, saw-grass marshes, hammocks and mangrove forest and in disturbed sites, roadsides, agricultural and drainage areas FerriterMost invasive in moist conditions but also tolerates dry conditions BrooksIn the non-coloured areas the plant is unlikely to establish as the climate, soil or landuse is not presently suitable.