Selective killing of choriocarcinoma cells in vitro by trichosanthin, a plant protein purified from root tubers of the Chinese medicinal herb Trichosanthes kirilowii

Tsao, Sai‐Wah; Yan, Keding; Yeung, H.W.

doi:10.1016/0041-0101(86)90108-x

Cited by 62 publications

(22 citation statements)

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“…(Cucurbitaceae) are the source of the bioactive protein TCN, a single-chain RIP (Wang et al, 1986;Maraganore et al, 1987). TCN is used to induce mid-term abortions and for treating ectopic pregnancies and trophoblastic tumors (Tsao et al, 1986;Yeung et al, 1988). TCN was shown by McGrath et al (1989) to inhibit human immunodeficiency virus 1 replication in human lymphocyte Plant Physiol.…”

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confidence: 99%

Biosynthesis of Defense-Related Proteins in Transformed Root Cultures of Trichosanthes kirilowii Maxim. var japonicum (Kitam.)

Savary

Flores

1994

Plant Physiol.

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We have established transformed ("hairy") root cultures from Trichosanthes kirilowii Maxim. var japonicum Kitam. (Cucurbitaceae) and four related species to study the biosynthesis of the ribosome-inactivating protein trichosanthin (TCN) and other rootspecific defense-related plant proteins. Stable, fast-growing root clones were obtained for each species by infecting in vitro grown plantlets with Agrobacferium rhizogenes American Type Culture Collection strain 15834. Each species accumulated reproducibly a discrete protein pattern in the culture medium. Analysis of the extracellular proteins from T. kirilowii var japonicum root cultures showed differential protein accumulation in the medium during the time course of growth in batch cultures. Maximum protein accumulation, approaching 20 pg/mL, was observed at mid-exponential phase, followed by a degradation of a specific protein subset that coincided with the onset of stationary phase. Two major extracellular proteins and one intracellular protein, purified by ion-exchange and reverse-phase high-performance liquid chromatography, were identified as class 111 chitinases (EC 3.2.1.14) based on N-terminal amino acid sequence and amino acid composition homologies with other class 111 chitinases. The Trichosanthes chitinases also showed reactivity with a cucumber class 111 chitinase antiserum and chitinolytic activity in a glycol chitin gel assay. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis of intracellular proteins showed that normal and transformed 7. kirilowii var japonicum roots accumulated only low levels of TCN (approximately 0.5% total soluble protein). Storage roots from the plant displayed protein and antigen patterns different from root cultures and produced TCN as the dominant protein. Roots undergoing secondary growth and differentiation exhibited patterns similar to those of storage roots, including increased TCN levels, indicating that high production of TCN is associated with induction of secondary growth in roots.Transformed ("hairy") root 'cultures have facilitated elucidation of root-specific metabolism in plants (Flores and Filner, 1985; Flores, 1987;Rhodes et al., 1990). Transformed root cultures stably express root-specific biosynthetic pathways and have been used to study extensively the biosynthesis of a wide range of low mol wt metabolites such as alkaloids, flavonoids, and polyacetylene and sesquiterpene phytoalexins (Rhodes et al., 1990;Flores and Curtis, 1992;Saito et al.,

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confidence: 99%

Biosynthesis of Defense-Related Proteins in Transformed Root Cultures of Trichosanthes kirilowii Maxim. var japonicum (Kitam.)

Savary

Flores

1994

Plant Physiol.

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“…TCS can inactivate the ribosome by removing adenine-4324 in 28 S rRNA, by N-glycosidase activity [30]. The increasing evidence to suggest that TCS has a broad spectrum of biological and pharmacological activities, including abortifacient, anti-tumour and anti-HIV activities [10][11][12][13][14][15][16][17][18], the proposed mechanisms of which include anti-tumour activity of the N-terminal sequences of TCS and anti-HIV action by the inhibition of HIV-1 integrase [13,14]. In this study we found for the first time that TCS-induced ROS are involved in the apoptosis of JAR cells.…”

Section: Discussionmentioning

confidence: 99%

“…Trichosanthin (TCS), a 27 kDa ribosome-inactivating protein (' RIP ') extracted from the root tuber of a traditional Chinese medicinal herb Trichosanthes kirilowiii, has been used for more than 1000 years in China to induce abortion owing to its high toxicity to trophoblasts. There is increasing evidence to suggest that TCS has a broad spectrum of biological and pharmacological activities, including abortifacient and anti-tumour activities [10][11][12][13]. Recent studies have shown that TCS possesses strong anti-HIV activity ; TCS inhibits the replication of HIV-1 in itro and decreases HIV markers in i o [14][15][16][17][18].…”

Section: Introductionmentioning

confidence: 99%

“…So far, good progress has been made with the elucidation of the anti-tumour and anti-HIV mechanism of TCS, including the observation that Nterminal sequences of TCS have anti-tumour activity and that the anti-HIV property of TCS is due to inhibition of HIV-1 integrase [13,14]. JAR cells (a human choriocarcinoma line) are sensitive to TCS and are a useful model for cell biological study [12]. Studying the effect of TCS on JAR cells will help us to understand better the anti-tumour and anti-HIV mechanism of TCS.…”

Section: Introductionmentioning

confidence: 99%

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Reactive oxygen species involved in trichosanthin-induced apoptosis of human choriocarcinoma cells

ZHANG¹,

GONG²,

MA³

et al. 2001

Biochemical Journal

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“…TCS has multiple pharmacological properties including anti-tumor, immunomodulatory and antiviral activity [12][13][14][15]. It is traditionally used to induce mid-term abortion in china.…”

Section: Introductionmentioning

confidence: 99%

Mapping the antigenic determinants and reducing the immunogenicity of trichosanthin by site-directed mutagenesis

Wei

et al. 2006

J Biomed Sci

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SummaryTrichosanthin (TCS) is a type I ribosome-inactivating protein (RIP) possessing multiple pharmacological properties. One of its interesting properties is to inhibit human immunodeficiency virus (HIV) replication but its strong immunogenicity has limited the repeated clinical administration. To map the antigenic determinants and reduce the immunogenicity of TCS, two potential antigenic sites (YFF81-83 and KR173-174) were identified by computer modeling, and then three TCS mutants namely TCS YFF81-83ACS , TCS KR173-174CG , and TCS YFF-KR were constructed by site-directed mutagenesis. The RI activity and DNase-like activity of the three constructed TCS mutants were similar to natural TCS but with much lower immunogenicity. Results suggested that the two selected sites are all located at or near the antigenic determinants of TCS. In toxicity studies, the LD 50 of the three TCS mutants was not different from natural TCS. These findings would be useful in designing a better therapeutic agent for AIDS.

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Selective killing of choriocarcinoma cells in vitro by trichosanthin, a plant protein purified from root tubers of the Chinese medicinal herb Trichosanthes kirilowii

Cited by 62 publications

References 9 publications

Biosynthesis of Defense-Related Proteins in Transformed Root Cultures of Trichosanthes kirilowii Maxim. var japonicum (Kitam.)

Biosynthesis of Defense-Related Proteins in Transformed Root Cultures of Trichosanthes kirilowii Maxim. var japonicum (Kitam.)

Reactive oxygen species involved in trichosanthin-induced apoptosis of human choriocarcinoma cells

Mapping the antigenic determinants and reducing the immunogenicity of trichosanthin by site-directed mutagenesis

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