strychnine and Necrosis

Sungucine (SG) and isosungucine (ISG) are bisindole alkaloids characterized by a 5'-23 link between the two parts of the compounds, which are till now specific to Strychnos icaja. In this work, SG and ISG were submitted to the NCI's in vitro 60 human tumor cell line screen, where SG showed interesting selectivity (6X) against the tested leukemia cell lines. In HL60-treated cells, apoptosis was demonstrated by observation of apoptotic bodies formation, and phosphatidylserine exposition at cell surface. In HeLa-treated cells, the analysis of cellular cycle by flow cytometry showed G1 accumulation and a small sub-G1 peak that could be related to DNA fragmentation characteristic of apoptosis. The eventual role of p53 was analyzed using wild-type HCT-116 colon cancer cells. Nevertheless, p53 and Bax expression were not modified in SG-treated cells. The cleavage of PARP by caspase-3 protease proved that apoptosis was also induced in this line. These results demonstrate that SG induces apoptosis, but also necrosis, in human cancer cell lines.

Topics: Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Division; Humans; Indole Alkaloids; Necrosis; Plant Roots; Strychnine; Strychnos; Tumor Cells, Cultured

We have previously shown that strychnine mimics the cytoprotective properties of glycine in renal proximal tubule (RPT) suspensions exposed to antimycin A (AA). The aims of this study were to determine whether the cytoprotective properties of strychnine applied to various types of nephrotoxicants and to examine the temporal aspects of the cytoprotection of glycine and strychnine. Tubular release of LDH activity was used as a marker of cell death. Glycine (2 mM) or strychnine (1 mM) added 5 min prior to the toxicant decreased LDH release in rabbit RPT suspensions exposed to 25 microM tetrafluoroethyl-L-cysteine (TFEC), 10 microM HgCl2, 0.5 mM t-butyl hydroperoxide (TBHP), or 0.2 mM bromohydroquinone (BHQ) for 4 hr, or 2 mM sodium cyanide (NaCN) for 2 hr. The relative rank order of effectiveness of glycine and strychnine was NaCN = TFEC > BHQ > DCVC >> TBHP > HgCl2. The temporal aspects of strychnine and glycine protection were examined by exposing RPT to either AA or TFEC for 1 or 3 hr, respectively, and then adding either 1 mM glycine or 1 mM strychnine. Glycine and strychnine decreased LDH release in AA-treated RPT at 1.25 and 2 hr and TFEC-treated RPT at 4 hr. In addition, when RPT exposed to AA or TFEC and treated with strychnine or glycine were washed at either 1 or 4 hr, protection was eliminated at later time points. When glycine was added to RPT treated with either PCBC, TFEC, or DCVC 5 min prior to or 30, 60, 120, and 180 min following toxicant addition, LDH release was reduced at all time points. These results demonstrate that strychnine and glycine protect RPT from a variety of diverse nephrotoxicants, strychnine and glycine do not need to be present at the time of toxic insult, strychnine and glycine cytoprotection is reversible, and strychnine and glycine act in the late phase of necrotic cell injury.

Topics: Animals; Antimycin A; Cell Death; Cysteine; Glycine; Hydrocarbons, Fluorinated; Hydroquinones; In Vitro Techniques; Kidney Tubules, Proximal; L-Lactate Dehydrogenase; Necrosis; Peroxides; Rabbits; Sodium Cyanide; Strychnine; tert-Butylhydroperoxide