Suppressive effects of novel derivatives prepared from Aconitum alkaloids on tumor growth

Abstract

Little information has so far been reported regarding the antiproliferative properties of Aconitum alkaloids against human tumor cells despite of their intense toxicities. In the present study, the antitumor properties and radiation sensitizing effects were investigated by various types of novel derivatives prepared from Aconitum alkaloids. The antitumor properties were investigated against human tumor cell lines, A172, A549, HeLa and Raji, respectively, by a cell growth, a clonogenic assay, cell cycle distribution, cell cycle related molecules and gammaH2AX expression. The novel compounds derived from C(20)-diterupenoid alkaloids showed a significantly suppressive effect in all cell lines. In contrast, natural C(19)-norditerpenoid alkaloids and their derivatives showed either no effect or only a slight effect. One of the compounds also showed radiosensitizing properties on A549 cells. These effects are not related to either the cell cycle distribution, the enhancement of apoptosis or the gammaH2AX expression. Novel derivatives prepared from Aconitum alkaloids, not but natural alkaloids, clearly showed anti-proliferative activity in human tumor cell lines.

Structure-activity relationships between the Aconitum C20-diterpenoid alkaloid derivatives and the growth suppressive activities of Non-Hodgkin’s lymphoma Raji cells and human hematopoietic stem/progenitor cells

“…1 a Core structures of natural C 19 -norditerpenoid and C 20 -diterpenod alkaloids. b The structure of C 20 -diterpenoid alkaloid and novel derivatives Isolation, purification and derivation were conducted according to previous studies [9,10]. The compounds were dissolved in DMSO (Wako, Osaka, Japan) at 1 mg/ml or 10 mg/ml.…”

“…However, the precise pharmacological properties of other minor alkaloids such as Aconitum C 20 -diterpenoid alkaloids which have the least toxicity [7], have not so far been reported regarding the precise pharmacological properties. Recently, we showed that some novel Aconitum C 20 -diterpenoid alkaloid derivatives have powerful suppressive properties against glioblastoma A172 cells [9] and radio-sensitizing effects against the human solid tumor cell line, A549 cells [10]. These effects showed a strong SAR related to their derivative sites although those suppressive activities depended on the derivative patterns and the cell types [9,10].…”

Novel Acridine-Based <i>N</i>-Acyl-homoserine Lactone Analogs Induce Endoreduplication in the Human Oral Squamous Carcinoma Cell Line SAS

“…18) In brief, treated SAS cells were harvested and lysed on ice for 30 min in 50 mM N-2-hydroxyethyl piperazine-N′-2-ethanesulfonic acid (Hepes)-HCl (pH 7.4), 100 mM NaCl, 1% Triton X-100, and 1 mM phenylmethylsulfonyl fluoride (PMSF) (Wako), then sonicated twice for 30 s at 4°C. After a 20-min centrifugation (12,000 rpm at 4°C), the supernatant was removed and the protein concentration was determined using the Bio-Rad protein assay kit (Bio-Rad Lab, Hercules, CA, U.S.A.) and a SmartSpecTM Plus spectrophotometer (Bio-Rad).…”

Caspase-independent apoptosis induction of quorum-sensing autoinducer analogs against chronic myeloid leukemia K562

“…SDS-PAGE and Western blotting was performed as described in a previous report [12]. Briefly, each cell was treated with each compound in the medium and incubated for 24 h. Harvested cells were lysed with 50 mM HepesHCl (pH 7.4), 100 mM NaCl, 1% Triton X-100, and 1 mM PMSF (Wako) on ice for 30 min and sonicated twice for 30 s at ice-cold temperature.…”