Opposite effects of nanocrystalline fullerene (C(60)) on tumour cell growth in vitro and in vivo and a possible role of immunosupression in the cancer-promoting activity of C(60).
In the present study, we compared the effects of nanocrystalline fullerene suspension (nanoC(60)) on tumour cell growth in vitro and in vivo. NanoC(60) suspension was prepared by solvent exchange using tetrahydrofuran to dissolve C(60). In vitro, nanoC(60) caused oxidative stress, mitochondrial depolarization and caspase activation, leading to apoptotic and necrotic death in mouse B16 melanoma cells. Biodistribution studies demonstrated that intraperitoneally injected radiolabeled (125I) nanoC(60) readily accumulated in the tumour tissue of mice subcutaneously inoculated with B16 cells. However, intraperitoneal administration of nanoC(60) over the course of two weeks starting from melanoma cell implantation not only failed to reduce, but significantly augmented tumour growth. The tumour-promoting effect of nanoC(60) was accompanied by a significant increase in splenocyte production of the immunoregulatory free radical nitric oxide (NO), as well as by a reduction in splenocyte proliferative responses to T- and B-cell mitogens ConcanavalinA and bacterial lipopolysaccharide, respectively. A negative correlation between NO production and splenocyte proliferation indicated a possible role of NO in reducing the proliferation of splenocytes from nanoC(60)-injected mice. These data demonstrate that nanoC(60), in contrast to its potent anticancer activity in vitro, can potentiate tumour growth in vivo, possibly by causing NO-dependent suppression of anticancer immune response.
Institute for Biological Research, Belgrade, Serbia.
Nevena S
NS
Zogovic
Nadezda S
NS
Nikolic
Sanja D
SD
Vranjes-Djuric
Ljubica M
LM
Harhaji
Ljubica M
LM
Vucicevic
Kristina D
KD
Janjetovic
Maja S
MS
Misirkic
Biljana M
BM
Todorovic-Markovic
Zoran M
ZM
Markovic
Slobodan K
SK
Milonjic
Vladimir S
VS
Trajkovic
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D037741:Fullerenes / Q000737:chemistry / Q000494:pharmacology; D007165:Immunosuppression Therapy; D008422:Materials Testing; D008546:Melanoma, Experimental / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000378:metabolism
D000970:Antineoplastic Agents; D037741:Fullerenes; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D020169:Caspases; C069837:fullerene C60