A conditioned medium from a human liposarcoma-derived cell line induces p53-dependent apoptosis in several tumor cell lines.
A novel cell line, named LSA, has been obtained, stabilized, and characterized from a human liposarcoma. These cells have morphological and biochemical features strongly resembling the adipocytes and were able to grow in the Ham's F12 medium, in presence or absence of FCS. A conditioned medium (LSA-CM) was obtained by growing the LSA cells in the F12 medium in the absence of FCS. LSA-CM had cytostatic and cytotoxic effects (apoptosis and necrosis) associated with down-regulation of c-myc and upregulation of p53 in several human cell lines (breast, lung, glioblastoma, etc. ). The MCF-7 and glioblastoma cells were killed by LSA-CM in 5-6 days, whereas the same cells were killed by LSA-CM co-incubated with low doses of cisplatin in 30 h. LSA-CM peri-tumoral injections for 15 days in Balb-c-fc3H mice affected by mammary tumors, resulted in the rapid disruption of tumors and absence of metastases. In contrast, in the untreated animals the tumor masses were 4 times larger than initial lesions, and numerous metastases were found in the lungs. The toxicity analysis of LSA-CM, performed on three different animal species, showed that LSA-CM is absolutely free of acute, subacute, and subchronic toxicity. The possible use of LSA-CM/cisplatin for cancer treatment is discussed.
Mancini
A
A
National Cancer Institute, Fondazione Pascale, 80110 Naples, Italy.
Borrelli
A
A
Masucci
M T
MT
Schiattarella
A
A
Filice
S
S
Rashan
J
J
Maggino
T
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity; D017077:Culture Media, Conditioned / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D005909:Glioblastoma; D006168:Guinea Pigs; D006801:Humans; D008080:Liposarcoma; D008175:Lung Neoplasms; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology*; D051379:Mice; D008809:Mice, Inbred C3H; D009152:Mutagenicity Tests; D009336:Necrosis; D009362:Neoplasm Metastasis / Q000517:prevention & control; D012486:Salmonella typhimurium / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
D017077:Culture Media, Conditioned; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin