Enhanced anti-tumor effects achieved in a murine tumor model using combination therapy of recombinant human manganese superoxide dismutase and adriamycin.

Manganese superoxide dismutase (MnSOD) is the only primary antioxidant enzyme in mitochondria that scavenges superoxide radicals. Overexpressing MnSOD in cancer cells by cDNA transfection suppresses tumor formation and reverses malignant growth. In this study, we examined the effect of recombinant human manganese superoxide dismutase (rhMnSOD) alone and in combination with adriamycin (ADR) against solid tumors of sarcoma 180 in Institute of Cancer Research (ICR) mice. Administration of rhMnSOD alone and in combination with ADR significantly inhibited tumor growth in a dose-dependent manner. The use of rhMnSOD in combination with ADR enhanced ADR's anti-tumor potency without increasing toxicity. Histopathological examination provided evidence of the anti-tumor effect. In addition, we found lymphocyte infiltration of the tumors, with an increase in both CD4- and CD8-positive cells in the treated tumors. The expression of CD4 and CD8 was up-regulated with increasing dose of rhMnSOD, and the combination treatment with ADR further enhanced this up-regulation. Collectively, these data indicate that rhMnSOD may exhibit an anti-tumor effect by stimulating the immune system and promoting the recruitment of lymphocytes into the tumor to kill tumor cells. Thus MnSOD may constitute a potential new therapeutic agent to be exploited as an adjuvant in cancer therapy.

[Antioxidant activity of natural and cultured Cordyceps sp].

OBJECTIVE: Investigating the antioxidant activities of water and ethanol extracts of natural Cordyceps sinensis and Cordyceps militaris and their fermentation preparations. METHOD: The samples were tested through 6 assays: inhibition ability of linoleic acid oxidation; scavenging activity of DPPH, hydrogen peroxide, hydroxyl radical and superoxide anion; and metal chelating activity. RESULT: Samples showed different antioxidant ability, and there was not an extract that exhibited high activity in all assays; however, water extract of natural C. militaris could be regarded as the most powerful antioxidant among 8 samples. It had high activity in inhibition of linoleic acid oxidation, chelating metal ions, and scavenging DPPH and hydroxyl radical. The research also indicated that the contents of phenolic compounds in water and ethanol extracts of natural and cultured Cordyceps sp. had huge difference. CONCLUSION: Natural Cordyceps sp. and its fermentation preparations could be used as potential natural antioxidants. The fermented process affected the antioxidant ability of cultured Cordyceps sp., and the antioxidant activity of both natural and cultured Cordyceps sp. did not significantly related with the quantity of phenolics.

Effect of nutrition factors on the synthesis of superoxide dismutase, catalase, and membrane lipid peroxide levels in Cordyceps militaris mycelium.

Effect of carbon, nitrogen, and metal ion sources on superoxide dismutase (SOD), catalase (CAT) activities, and lipid perioxide (LPO) levels in Cordyceps militaris mycelium were investigated at stationary growth phase by step supplementing with these nutrition factors in shake-flask cultures. Mycelium was cultivated in several growth media containing different carbon sources. The observed highest SOD and CAT activities were 44.3 U/mg protein in the presence of 20% potato broth plus 2% glucose medium and 93.7 U/mg protein in presence of 20% potato broth plus 1% glucose medium, respectively. By supplementing with either yeast extract or tryptone in 0.1-0.5% concentration range, the highest SOD and CAT activities were 21.1 U/mg protein in medium supplemented with 0.1% yeast extract and 20.7 U/mg protein in medium supplemented with 0.1% tryptone, respectively. Supplementing with Cu(2+), Zn(2+), and Mn(2+) caused a stimulation of SOD synthesis. The minimum LPO level was observed at media presented Zn(2+). The time course of SOD and CAT biosynthesis showed two maxima, which correspond to the maximum of biomass. High SOD levels and low LPO levels in the medium described above indicated that the appropriate metal ions could provide a suitable protection for cells against oxygen radical damage.