DNA intercalation, topoisomerase II inhibition and cytotoxic activity of the plant alkaloid cryptolepine

in Anti-Cancer Drug Design (2000), 15(3), 191-201

Cryptolepine and neocryptolepine are two indoloquinoline alkaloids isolated from the roots of the African plant Cryptolepis sanguinolenta. Both drugs have revealed antibacterial and antiparasitic ... [more ▼]

Cryptolepine and neocryptolepine are two indoloquinoline alkaloids isolated from the roots of the African plant Cryptolepis sanguinolenta. Both drugs have revealed antibacterial and antiparasitic activities and are strongly cytotoxic to tumour cells. We have recently shown that cryptolepine can intercalate into DNA and stimulates DNA cleavage by human topoisomerase II. In this study, we have investigated the mechanism of action and cytotoxicity of neocryptolepine, which differs from the parent isomer only by the orientation of the indole unit with respect to the quinoline moiety. The biochemical and physicochemical results presented here indicate that neocryptolepine also intercalates into DNA, preferentially at GC-rich sequences, but exhibits a reduced affinity for DNA compared with cryptolepine. The two alkaloids interfere with the catalytic activity of human topoisomerase II but the poisoning activity is slightly more pronounced with cryptolepine than with its isomer. The data provide a molecular basis to account for the reduced cytotoxicity of neocryptolepine compared with the parent drug. [less ▲]

Effect of nicotine on rat gingival fibroblasts in vitro

in Connective Tissue Research (2000), 41(1), 69-80

Nicotine from 3 to 5 mM affects growth and survival rate of rat gingival fibroblasts in vitro. Ultrastructural analysis revealed dilated mitochondria and vacuolization in treated cells, suggestive of ... [more ▼]

Nicotine from 3 to 5 mM affects growth and survival rate of rat gingival fibroblasts in vitro. Ultrastructural analysis revealed dilated mitochondria and vacuolization in treated cells, suggestive of necrosis, but increased apoptosis was also revealed by cytometry. On the basis of this in vitro study, it appear that tobacco, through its component nicotine, may directly affect various functions of rat gingival fibroblasts [less ▲]

In vitro activity of african Strychnos alkaloids against chloroquine resistant plasmodium falciparum

Poster (1999)

Cryptolepine is a potent DNA intercalating agent which inhibits selectively DNA synthesis in B16 melanoma cells cultured in vitro

Poster (1998, January)

In Vitro Cytotoxic Activity of Two Potential Anticancer Drugs Isolated from Strychnos: Strychnopentamine and Usambarensine

in Anticancer Research (1996), 16(3A, May-Jun), 1129-37

The cytotoxicity and the selective antiprotozoal activity of some Strychnos alkaloids, namely strychnopentamine (SP) and usambarensine (US) (7) led us to analyze and compare their effects with emetine (EM ... [more ▼]

The cytotoxicity and the selective antiprotozoal activity of some Strychnos alkaloids, namely strychnopentamine (SP) and usambarensine (US) (7) led us to analyze and compare their effects with emetine (EM) by using mouse B16 melanoma cells cultivated in vitro. We observed by cytological analysis and proliferation rate studies that these substances induce analogous cytotoxic effects in B16 cells, but at different concentrations i.e. formation of lamellar bodies in the cytoplasm, the which contain pre-melanosomes in the case of SP and US, vacuoles and blebs. At concentrations near their respective IC50, SP and US, but not EM, decreased colony formation. We showed by incorporation of labelled precursors that SP and US first inhibit RNA synthesis while EM initially acts on protein synthesis. These alkaloids increased melanin synthesis. Furthermore, only EM and SP caused hemolysis of sheep red blood corpuscles. This could explain why the rate of antiplasmodial activity is higher for SP and EM. [less ▲]

Purification and analysis by mass spectometry of low M.W. soluble factors released into conditioned culture media by B16 melanoma cells

Poster (1995, July)

Effects of Alpha-Hederin, a Saponin Extracted from Hedera Helix, on Cells Cultured in Vitro

in Planta Medica (1994), 60(1), 45-9

In this work, we have analysed the effects of alpha-hederin, a monodesmosidic triterpenoid saponin isolated from Hedera helix, on mouse B16 melanoma cells and non-cancer mouse 3T3 fibroblasts cultured in ... [more ▼]

In this work, we have analysed the effects of alpha-hederin, a monodesmosidic triterpenoid saponin isolated from Hedera helix, on mouse B16 melanoma cells and non-cancer mouse 3T3 fibroblasts cultured in vitro. Our results indicate that, in a serum-free medium, alpha-hederin is cytotoxic and inhibits proliferation in both cell lines at rather low concentrations (< 5 micrograms/ml) after only 8 hours of treatment. Its cytotoxicity decreases in the presence of serum in which BSA seems to be able to bind the saponin. alpha-Hederin also induces vacuolization of the cytoplasm and membrane alterations leading to cell death. [less ▲]

Effect of selenium compounds on murine B16 melanoma cells and pigmented cloned pB16 cells

in Archives of Toxicology (1994), 68(4), 246-254

Seleno-DL-cysteine and sodium selenate are toxic in B16 cells and this toxicity seems to involve glutathione metabolites.

Characterization and Tumorigenicity of Spheroids Composed of Pigmented or Non Pigmented B16 Melanoma Cells

in In Vivo (Athens, Greece) (1994), 8(3, May-Jun), 333-8

A parental line of mouse B16 melanoma cells (B16) and two derived cloned lines, either pigmented (B16P) or non pigmented (B16NP), were cultured in vitro as spheroids. After 48 hrs, the pigmented cells ... [more ▼]

A parental line of mouse B16 melanoma cells (B16) and two derived cloned lines, either pigmented (B16P) or non pigmented (B16NP), were cultured in vitro as spheroids. After 48 hrs, the pigmented cells (B16, B16P) formed smaller and looser aggregates, with higher rates of cell proliferation and lower amounts of extracellular matrix as compared to B16NP spheroids. The three lines were more tumorigenic when inoculated subcutaneously as spheroids than as isolated cells. Furthermore, B16P or B16 spheroids developed richly vascularized subcutaneous tumors and metastases more rapidly than B16NP aggregates. After intravenous injection of spheroids, the measurement with an image analyzer of the area of sections in lung colonies indicated that B16P colonies were larger and more numerous than those induced by B16NP cells. [less ▲]

Effects of α-Hederin on cells cultured in vitro

Poster (1993, June)