The inhibition of neoplastic cell proliferation with human natural tumor necrosis factor.
Purified human natural tumor necrosis factor (n-TNF) was prepared by stimulating human leukemic B cell line (BALL-1) with Sendai virus. The colony formations of all of 18 human cancer-derived abnormal cell lines were suppressed by 10(1)-10(6) U/ml of n-TNF, while n-TNF was nontoxic to all human normal fibroblast cells. This in vitro inhibition of cell growth was reversible. In breast adenocarcinoma MCF7 cells treated with n-TNF a specific decrease of DNA synthesis was observed, and DNA histograms showed a block at G1 in the cell cycle. In vivo studies revealed that n-TNF suppressed the tumor growth of murine Meth A sarcoma, human renal adenocarcinoma (ACHN), malignant melanoma (SK-MEL-28) and glioblastoma (U-373 MG). Isobologram analysis showed that n-TNF synergistically inhibited cell growth in combination with human natural interferon (IFN)-a. In vivo synergism of n-TNF and IFN-a was also found in the U-373 MG tumor model implanted into nude mice.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004357:Drug Synergism; D006023:Glycoproteins / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000032:analysis; D018124:Receptors, Tumor Necrosis Factor; D012513:Sarcoma, Experimental / Q000628:therapy; D014409:Tumor Necrosis Factor-alpha
D006023:Glycoproteins; D007370:Interferon Type I; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha