Phytochemical investigation and in vitro cytotoxic evaluation of alkaloids from Abuta rufescens.

A phytochemical investigation of Abuta rufescens was performed to authenticate plant material reported previously and to assess the cytotoxicity of the alkaloids obtained from the plant. Three alkaloids which have not previously been reported from this species, two phenolic (subsessiline, an oxoaporphine, and telitoxine, an azafluoranthene) and one non-phenolic (isoimerubrine, a tropoloisoquinoline), were isolated and identified. These alkaloids, along with others previously isolated from this and another Abuta species (grandirubrine, a tropoloisoquinoline), were evaluated for cytotoxic activity against several human cancer cell lines (HCT-116 colon adenocarcinoma, ACHN renal carcinoma, and A549 lung carcinoma).

A unique paclitaxel-mediated modulation of the catalytic activity of topoisomerase IIalpha.

Paclitaxel (Taxol) is known to act by polymerizing and stabilizing microtubules. In spite of a known target, the existence of additional targets is suggested by a poor understanding of the mechanism(s) underlying eventual cell death by paclitaxel and by the drug's high efficacy, as compared to other spindle poisons. Based on the enhanced sensitivity of a mutant DNA double-strand break repair-deficient Chinese hamster ovary cell line to paclitaxel as well as to various topoisomerase (Topo) II poisons, it was hypothesized that paclitaxel, in addition to having an effect on microtubules, may also alter the activity of Topo II.

Growth inhibitory effect of L-canavanine against MIA PaCa-2 pancreatic cancer cells is not due to conversion to its toxic metabolite canaline.

L-Canavanine (CAV) is an arginine (ARG) analog isolated from the jack bean, Canavalia ensiformis. CAV becomes incorporated into cellular proteins of MIA PaCa-2 human pancreatic cancer cells and the aberrant, canavanyl proteins are not preferentially degraded. Hydrolytic cleavage of CAV to canaline (CAN) and urea is mediated by arginase.

Combination therapy with 5-fluorouracil and L-canavanine: in vitro and in vivo studies.

L-Canavanine (CAV) is a potent L-arginine antagonist, produced by legumes such as the jack bean, Canavalia ensiformis. CAV is cytotoxic to MIA PaCa-2 human pancreatic cancer cells. We sought to determine whether CAV's efficacy as an anticancer agent might be increased in combination with 5-fluorouracil (5-FU), a pyrimidine antimetabolite with activity against solid tumors.

Inhibition of the growth of human pancreatic cancer cells by the arginine antimetabolite L-canavanine.

L-Canavanine (CAV), the L-2-amino-4-guanidinooxy structural analogue of L-arginine (ARG), is a potent ARG antagonist which occurs in the jack bean, Canavalia ensiformis. This ARG antimetabolite is active against L1210 murine leukemia and a solid colonic tumor in the rat. Our initial studies using a microtiter assay show that CAV exhibits a 50% inhibitory concentration of approximately 2 mM against the human pancreatic adenocarcinoma cell line, MIA PaCa-2, when these cells are grown in Dulbecco's modified Eagle's medium containing 0.