Dataset Information

ATP-binding cassette transporter controls leaf surface secretion of anticancer drug components in Catharanthus roseus.

ABSTRACT: The Madagascar periwinkle (Catharanthus roseus) is highly specialized for the biosynthesis of many different monoterpenoid indole alkaloids (MIAs), many of which have powerful biological activities. Such MIAs include the commercially important chemotherapy drugs vinblastine, vincristine, and other synthetic derivatives that are derived from the coupling of catharanthine and vindoline. However, previous studies have shown that biosynthesis of these MIAs involves extensive movement of metabolites between specialized internal leaf cells and the leaf epidermis that require the involvement of unknown secretory processes for mobilizing catharanthine to the leaf surface and vindoline to internal leaf cells. Spatial separation of vindoline and catharanthine provides a clear explanation for the low levels of dimers that accumulate in intact plants. The present work describes the molecular cloning and functional identification of a unique catharanthine transporter (CrTPT2) that is expressed predominantly in the epidermis of young leaves. CrTPT2 gene expression is activated by treatment with catharanthine, and its in planta silencing redistributes catharanthine to increase the levels of catharanthine-vindoline drug dimers in the leaves. Phylogenetic analysis shows that CrTPT2 is closely related to a key transporter involved in cuticle assembly in plants and that may be unique to MIA-producing plant species, where it mediates secretion of alkaloids to the plant surface.

SUBMITTER: Yu F

PROVIDER: S-EPMC3785729 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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ATP-binding cassette transporter controls leaf surface secretion of anticancer drug components in Catharanthus roseus.

Yu Fang F De Luca Vincenzo V

Proceedings of the National Academy of Sciences of the United States of America 20130909 39

The Madagascar periwinkle (Catharanthus roseus) is highly specialized for the biosynthesis of many different monoterpenoid indole alkaloids (MIAs), many of which have powerful biological activities. Such MIAs include the commercially important chemotherapy drugs vinblastine, vincristine, and other synthetic derivatives that are derived from the coupling of catharanthine and vindoline. However, previous studies have shown that biosynthesis of these MIAs involves extensive movement of metabolites ...[more]

PMID: 24019465

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Project description:Catharanthus roseus (C. roseus) and ursolic acid (UA) are ayurvedic medicines with multiple pharmacological activities including antidiabetic activity, but till date, no study is available on their combination. This study documented the antidiabetic efficacy of the combination of C. roseus and UA in rats. Rats were divided into six groups. All groups were given a single dose of Streptozotocin (STZ) at a dose of 50?mg/kg by intraperitoneal route for induction of diabetes, except the normal control group. Group 1 was treated as a normal control (NC) group and fed with saline water, Group 2 as a Diabetes Control group, Group 3 as a STZ+C. roseus ethanolic extract (CREE) group at 50?mg/kg p.o., Group 4 as a STZ+UA group orally at 50?mg/kg, Group 5 as a STZ+CREE (25?mg/kg p.o.)+UA (25?mg/kg p.o.) group, and Group 6 as a STZ+Glimepiride (0.1?mg/kg) group. Diabetes was confirmed after 72 hours by estimation of blood glucose level, and then treatment was given for the next 28 days. During the course of treatment, plasma insulin and blood glucose were measured regularly at the interval of 7 days. At the end of the protocol, blood was collected and animals were sacrificed. The glucose level, insulin level, liver glycogen storage level, and antioxidant enzymes (LPO, CAT, SOD, GPx, GST) were measured. The blood glucose level in Group 5 significantly (P < 0.001) reduced to 98.35 ± 2.45?mg/dl in comparison with that in Group 2 (321.75 ± 5.46?mg/dl). The level of plasma insulin in Group 5 increased (13.65 ± 0.10??U/ml) significantly (P < 0.01) as compared with that in Group 2 (05.93 ± 0.31??U/ml). In Group 5, the level of glycogen in liver was significantly (P < 0.01) increased as compared with that in Group 2 rats. The level of antioxidant enzymes in Group 5 restored toward normal values significantly (P < 0.01; P < 0.001) as compared with that in Group 2 animals. These findings suggest that low-dose combination of CREE and UA is effective in the treatment of diabetes.

Dataset Information

ATP-binding cassette transporter controls leaf surface secretion of anticancer drug components in Catharanthus roseus.

Publications

ATP-binding cassette transporter controls leaf surface secretion of anticancer drug components in Catharanthus roseus.

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