Tamoxifen and trifluoroperazine (Stelazine) potentiate cytostatic/cytotoxic effects of P-30 protein, a novel protein possessing anti-tumor activity.
P-30 protein, a novel protein isolated in our laboratory from fertilized Rana pipiens eggs, has been shown to possess significant anti-proliferative and cytotoxic activity against a variety of human tumour cell lines. This protein also shows a potent anti-tumour activity in vivo in animal tumour models and is currently undergoing Phase I human clinical trials in cancer patient volunteers. The present study describes the in vitro effects of the concerted action of this protein and two other agents which affect the cell proliferative cycle. A significant potentiation of the P-30 protein-induced cell growth inhibition by tamoxifen as well as trifluoroperazine (Stelazine) in both the human A-549 lung carcinoma and the ASPC-1 pancreatic adenocarcinoma systems at wide ranges of drug concentrations was observed. The effect was apparently due to the synergistic action of P-30 protein and the agents tested. This data may provide clues that can be useful in explaining the mechanism of its anti-tumour activity. The results are also helpful for the designing in vivo animal and, perhaps eventually, human studies, whereby the combination therapies utilizing P-30 protein with agents of relatively low toxicity such as tamoxifen and/or Stelazine could offer a promising treatment(s) for these notoriously refractory types of human cancer.
Mikulski
S M
SM
Alfacell Corporation, Bloomfield, New Jersey 07003.
Viera
A
A
Ardelt
W
W
Menduke
H
H
Shogen
K
K
D000230:Adenocarcinoma / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D011506:Proteins / Q000494:pharmacology*; D012260:Ribonucleases; D013629:Tamoxifen / Q000494:pharmacology*; D014268:Trifluoperazine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011506:Proteins; D013629:Tamoxifen; D014268:Trifluoperazine; D012260:Ribonucleases; C058703:ranpirnase