Activity of novel plant extracts against medullary thyroid carcinoma cells. Anticancer Res

Department of Pathophysiology, Medical University of Graz, Heinrichstrasse 31, A-8010 Graz, Austria.
Anticancer research (Impact Factor: 1.83). 01/2004; 24(2A):495-500.
Source: PubMed

ABSTRACT Medullary thyroid carcinoma (MTC) is a rare calcitonin-producing tumor, derived from the parafollicular C-cells of the thyroid. MTC is known to be relatively insensitive to conventional chemotherapy.
Eight cell lines were established from MTCs; each showed an up-regulation of Bcl-2. We investigated ten agents from plants of the genera Stemona (Stemonaceae), Aglaia (Meliaceae) and Artemisia (Asteraceae) for their effects on proliferation and apoptotic rates. Extracts have been used in traditional Chinese medicine; however, no experience on their effects on medullary thyroid carcinomas has been reported so far. Growth kinetics and viability were examined using the Casy-1-Cell Counter & Analyzer and the WST-1-based cytotoxicity assay. Apoptosis was studied by DAPI staining, by measurement of caspase-3 activity and Bcl-2 expression.
A strong antiproliferative effect was recognized in each Aglaia species and with Artesunate, whereas an enhancement of apoptosis was provoked particularly by Stemona tuberosa Lour.
The activity of the novel plant extracts possiby offers a new approach towards successful chemotherapy of the so far chemo-resistant medullary thyroid carcinoma.

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    • "This pathway plays a major role in drug-induced apoptosis (Schmitt et al 2000) whereas we found here that caspase 9 was not activated by ST-2. Together with our previous study (Rinner et al 2004) in which the expression of the antiapoptotic protein bcl-2 was not found to have changed by total ST-extracts, we assume Figure 5 ST-2 infl uenced the MTC-SK aggregation and morphology. (A) Cellular morphology. "
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    ABSTRACT: Medullary thyroid carcinoma (MTC), a neuroendocrine tumor arising from the thyroid gland, is known to be poorly responsive to conventional chemotherapy. The root of Stemona tuberosa Lour, also called Bai Bu, is a commonly used traditional Chinese anti-tussive medicine. The present study investigated this medicinal herb for the first time with respect to its anticancer activity in human medullary thyroid carcinoma cells. Four extracts of Stemona tuberosa Lour, including the n-hexane fraction, (ST-1), dichloromethane (DCM) fraction, (ST-2), ethyl acetate (EtOAc) fraction, (ST-3), and methanol fraction, (ST-4) were examined for antiproliferative effects in two MTC cell lines. We observed that only the DCM fraction ST-2 inhibited cell growth and viability in a dose-dependent manner. Furthermore, we found that ST-2 also induced the apoptosis of MTC-SK cells. Caspase-3/7 was activated, while caspase-9 was not, implying that at least a caspase-dependent apoptotic pathway was involved in this process. In addition, the multicellular spheroids of MTC-SK were destroyed and the cell morphology was changed by ST-2. Our results show the strong apoptotic effects of the DCM fraction of Stemona tuberosa Lour on human medullary thyroid carcinomas, so suggesting a new candidate for chemotherapy of the so far chemo-resistant medullary thyroid carcinoma.
    Targets & therapy 01/2008; 1(4):455-63.
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    • "Intermediate IC 50 values were obtained for melanomas, breast, ovarian, prostate, CNS, and renal cancer cell lines (Efferth et al., 2001). Artesunate also inhibited the growth of medullary thyroid carcinoma cells (Rinner et al., 2004). The IC 50 values for artesunate correlated significantly with the cell doubling times and the portion of cells in the G0/G1 or S cell cycle phases of the NCI cell lines (Efferth et al., 2003a). "
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    ABSTRACT: In addition to their well-known anti-malarial activity, artemisinin and its derivatives (1,2,4-trioxanes) possess potent activity against tumor cells in the nano- to micromolar range. Candidate genes that may contribute to the sensitivity and resistance of tumor cells to artemisinins were identified by pharmacogenomic and molecular pharmacological approaches. Target validation was performed using cell lines transfected with candidate genes or corresponding knockout cells. These genes are from classes with different biological function; for example, regulation of proliferation (BUB3, cyclins, CDC25A), angiogenesis (vascular endothelial growth factor and its receptor, matrix metalloproteinase-9, angiostatin, thrombospondin-1) or apoptosis (BCL-2, BAX). Artesunate triggers apoptosis both by p53-dependent and -independent pathways. Anti-oxidant stress genes (thioredoxin, catalase, gamma-glutamyl-cysteine synthetase, glutathione S-transferases) as well as the epidermal growth factor receptor confer resistance to artesunate. Cell lines over-expressing genes that confer resistance to established anti-tumor drugs (MDR1, MRP1, BCRP, dihydrofolate reductase, ribonucleotide reductase) were not cross-resistant to artesunate, indicating that this drug has a different target and is not subject to multidrug resistance. The Plasmodium translationally controlled tumor protein (TCTP) represents a known target protein of artemisinin and its derivatives in the malaria parasite. The microarray-based mRNA expression of human TCTP correlated with sensitivity to artesunate in tumor cells, suggesting that human TCTP contributes to response of tumor cells to the drug. The multi-factorial nature of cellular response to artemisinin and its derivatives may be beneficial to treat otherwise drug-resistant tumors and may explain why resistance development has not been observed in either cancer or malaria.
    Drug Resistance Updates 02/2005; 8(1-2):85-97. DOI:10.1016/j.drup.2005.04.003 · 9.12 Impact Factor
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    ABSTRACT: In the present review, we give a short introduction into the history, philosophy and traditional diagnosis and therapy of Kampo, which has its origins in traditional Chinese medicine. The main focus is on pharmacogenomics of natural products derived from Kampo medicinal plants, with special emphasis on cancer treatment. One of these natural products with profound cytotoxicity against tumor cell lines is shikonin from the medicinal plant Lithospermum erythrorhizon. This compound has been selected to demonstrate how molecular determinants of response of tumor cells to Kampo-derived natural products can be investigated by microarray-based approaches. Synthetic or semi-synthetic derivatives of natural products from Kampo medicine may lead to novel drugs with improved features for cancer treatment. Kampo-derived natural products represent a valuable reservoir for individual tumour treatment strategies in the future.
    Cancer genomics & proteomics 03/2007; 4(2):81-91. · 2.70 Impact Factor
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