Cytostatic and cytotoxic effects of Pannon (P-30 Protein), a novel anticancer agent.
P-30 Protein is a novel protein, of molecular weight approximately 15 KD, obtained from the extract of a vertebrate tissue showing in vivo antitumour activity. Cytostatic and cytotoxic effects of this product in its purified form (P-30 Protein) or in partially purified extracts (Pannon) were studied in vitro on human leukaemic HL-60, human submaxillary carcinoma A-253, human colon adenocarcinoma Colo 320 CM and murine erythroleukaemia (Friend leukaemia) cell lines. Of these cells, HL-60, A-253 and Colo 320 CM were sensitive and Friend leukaemia resistant to this agent. The effects were time- and concentration-dependent. During the initial 24-48 h of treatment, a slowdown in cell proliferation was apparent but cell death was not extensive. After 24-48 h, there was a reduction in the proportion of cells in S phase of the cell cycle and the cells became preferentially arrested in G1 phase. The G1 cells showed high heterogeneity with respect to RNA content and some cells were characterized by very low RNA content. Progressive cell death occurred in cultures maintained with Pannon for up to 7 d in proportion to its concentration. Reductions of 50 and 90% in clonogenicity of A-253 cells were observed during their growth in the presence of 0.13 and 1.5 micrograms/ml of this protein, respectively. Exponentially growing cells were more sensitive to Pannon compared with cells from confluent cultures. Colonies of A-253 cells growing in the presence of Pannon were much smaller in size compared with control colonies, indicating that the rate of proliferation of clonogens is reduced by this agent. It appears that P-30 Protein induces cytostatic effects via modulation of cell transition to quiescence or differentiation. The mechanism of its cytotoxic activity is unclear.
Darzynkiewicz
Z
Z
Sloan-Kettering Institute for Cancer Research, Walker Laboratory, Rye, NY 10580.
Carter
S P
SP
Mikulski
S M
SM
Ardelt
W J
WJ
Shogen
K
K
D000818:Animals; D000970:Antineoplastic Agents; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000032:analysis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008970:Molecular Weight; D011506:Proteins / Q000633:toxicity*; D012334:RNA, Neoplasm / Q000032:analysis; D012260:Ribonucleases; D013045:Species Specificity; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D011506:Proteins; D012334:RNA, Neoplasm; D012260:Ribonucleases; C058703:ranpirnase