Abrin and Ricin: New Anti-tumour Substances

Lin, Jung‐Yaw; Tserng, Kou‐Yi; Chen, Chi-Ching; Lin, Lee-Tzu; Tung, Ta‐Cheng

doi:10.1038/227292a0

Cited by 175 publications

(75 citation statements)

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“…THE TOXIC plant proteins, abrin and ricin, have been shown to inhibit the growth of Ehrlich ascites tumour cells in mice, and of cervical carcinoma in humans (Lin et al, 1970b;Tung, Hsu and Lin, 1971). The biochemical mechanism of action of these toxins has recently been elucidated.…”

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confidence: 99%

Toxicity, distribution and elimination of the cancerostatic lectins abrin and ricin after parenteral injection into mice

Fodstad¹,

Olsnes²,

Pihl³

1976

Br J Cancer

116

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Summary.-The survival time of mice after i.v. injection of the cancerostatic lectins, abrin and ricin, was recorded. The LD50 dose was found to be 10-13 ng and 55-65 ng per mouse for abrin and ricin, respectively. Increasing amounts of toxin reduced the survival time, reaching a minimum of about 10 h. Lactose injected with ricin, provided partial protection against ricin, as measured by the survival time.Abrin and ricin labelled with 1251, and shown to retain their full toxic activity, were injected into mice. Most of the radioactivity found in the organs was present in the form of intact toxins, at least up to 5 h after injection. After i.v. injection the highest concentration/g tissue was found in spleen, followed by kidneys, heart, liver and thymus. The relative concentration in liver was considerably higher for ricin than for abrin. Similar results were found after i.p. injection. When lactose was administered together with ricin, almost 80% of the ricin injected was found in the liver after 30 min, compared to 48% without lactose, and the amount in other organs was concurrently reduced.The elimination of total radioactivity was much faster for ricin than abrin. The radioactivity found in the urine was largely present in non-trichloroacetic acid precipitable form, indicating that the toxins were extensively degraded before excretion.

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confidence: 99%

Toxicity, distribution and elimination of the cancerostatic lectins abrin and ricin after parenteral injection into mice

Fodstad¹,

Olsnes²,

Pihl³

1976

Br J Cancer

116

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“…The first attempts to use ricin as a cancer therapeutic were based on its higher cytotoxicity in transformed cells (16), a mechanism that today would be called "targeted toward cancer-related glycostructures." Its development, however, failed due to unexpectedly high toxicity (17).…”

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Evaluation of Riproximin Binding Properties Reveals a Novel Mechanism for Cellular Targeting

Bayer

Essig

Stanzel

et al. 2012

Journal of Biological Chemistry

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Background: Riproximin is a cytotoxic lectin from Ximenia americana showing tumor selectivity. Results: Riproximin selectively binds to two types of glycoconjugates present on glycoproteins, cross-linking them by its two binding sites. Conclusion:The biologic activity of riproximin is determined by specific and dynamic interactions with multivalent, cancerrelated glycan targets. Significance: The selectivity of riproximin for cancer cells relies on its unique targeting mechanism.

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“…Studies have shown that some proteins, including Abrin (ABR), purified from A. precatorius, induce apoptosis in various types of cancer cells (Shih et al 2001;Narayanan et al 2004). Also Abrus lectins are considered as potential anticancer agents due to their apoptosis-inducing activity (Lin et al 1970). Abrins are more toxic to tumour cells than normal cells (Harborne et al 1999).…”

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confidence: 99%

Cytotoxic and pro-apoptotic effects of Abrus precatorius L. on human metastatic breast cancer cell line, MDA-MB-231

et al. 2012

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Abrus precatorius is highly regarded as a universal panacea in the herbal medicine with diverse pharmacological activity spectra. This experimental study on the mechanism of the anticancer activity of A. precatorius leaf extracts, may offer new evidence for A. precatorius in the treatment of breast cancer in clinical practice. Cell death was determined by using MTT assay. Further analyses were carried out by doing DNA laddering, PARP cleavage, FACS, semi-quantitative RT-PCR and detection of cellular reactive oxygen species (ROS) by DCFDA assay. A. precatorius showed very striking inhibition on MDA-MB-231 cells. MTT assay showed more than 75 % inhibition of the cells and treated cells indicated visible laddering pattern with thick compact band. PARP cleavage produced 89 kDa cleavage product which was associated with apoptosis. Flow cytometer exhibited a sub-G0/G1 peak as an indicative of apoptosis. mRNA expression level of apoptosis-related genes p21 and p53 was markedly increased in cells treated with the extract as compared to control. The up-regulation of p21 and p53 may be the molecular mechanisms by which A. precatorius extract which induces apoptosis. An increase in the concentration of A. precatorius extract does not generate ROS, instead it reduces ROS formation in MDA-MB-231 cells, as evident from the shift in fluorescence below untreated control. This is the first report showing that A. precatorius leaf extract exhibits a growth inhibitory effect by induction of apoptosis in MDA-MB-231 cells. Our results contribute towards validation of the A. precatorius extract as a potentially effective chemopreventive or therapeutic agent against breast cancer.

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Abrin and Ricin: New Anti-tumour Substances

Cited by 175 publications

References 1 publication

Toxicity, distribution and elimination of the cancerostatic lectins abrin and ricin after parenteral injection into mice

Toxicity, distribution and elimination of the cancerostatic lectins abrin and ricin after parenteral injection into mice

Evaluation of Riproximin Binding Properties Reveals a Novel Mechanism for Cellular Targeting

Cytotoxic and pro-apoptotic effects of Abrus precatorius L. on human metastatic breast cancer cell line, MDA-MB-231

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