Anticancer activity of novel plant extracts from Trailliaedoxa gracilis (W. W. Smith & Forrest) in human carcinoid KRJ-I Cells.
BACKGROUND
Small intestinal (SI) neuroendocrine tumors (NETs) are rare neoplasms derived from neuroendocrine cells presenting distinct clinical symptoms according to the ability to secrete neuroamines. Nevertheless, many are asymptomatic and misdiagnosed. As response rates to chemotherapy are low, surgery remains the only effective treatment. Because many tumors have metastasized at the time of diagnosis, curative surgery is rarely achieved. Consequently, a substantial need for new therapeutic options has emerged.


METHODS
The effects of novel plant extracts from Trailliaedoxa gracilis (W.W. Smith & Forrest) were investigated in the SI-NET cell line KRJ-I and in KRJ-I transplanted mice. Proliferation and viability were analyzed using cell counting and WST-1 cell proliferation assay. Apoptosis was determined by DAPI staining and electron microscopy, and quantified by luminescence assays for caspases 3/7, 6, 8, 9 and 2.


RESULTS
Extracts of Trailliaedoxa gracilis showed a dose-dependent reduction of proliferation and induction of apoptosis in the KRJ-I cells. Normal fibroblasts were not impaired. Tumor growth inhibition was also observed in heterotransplanted SCID (severe combined immunodeficiency) mice.


CONCLUSIONS
The in vitro and in vivo outcomes suggest a potential clinical effect of Trailliaedoxa gracilis in SI-NETs.
Department of Pathophysiology and Immunology, Medical University of Graz, Heinrichstrasse 31, A-8010 Graz, Austria.
Bernhard
B
Svejda
Victor
V
Aguiriano-Moser
Sonja
S
Sturm
Harald
H
Höger
Elisabeth
E
Ingolic
Veronika
V
Siegl
Hermann
H
Stuppner
Roswitha
R
Pfragner
D000818:Animals; D002276:Carcinoid Tumor / Q000188:drug therapy* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D007421:Intestine, Small / Q000473:pathology; D051379:Mice; D016513:Mice, SCID; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology; D019666:Rubiaceae / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
D010936:Plant Extracts; D053148:Caspase 3; D053179:Caspase 7