Endogenous tumor necrosis factor functions as a resistant factor against adriamycin

Area of Science:

• Molecular Biology
• Cell Biology
• Biochemistry

Background:

• Tumor necrosis factor (TNF) and heat induce cytotoxicity via reactive oxygen molecules.
• Endogenous TNF (enTNF) confers resistance to exogenous TNF and heat by upregulating manganous superoxide dismutase (MnSOD) to neutralize reactive oxygen species.

Purpose of the Study:

• To investigate if enTNF protects against adriamycin-induced cytotoxicity through a similar mechanism involving MnSOD.
• To explore the role of enTNF in cellular defense against chemotherapy-induced oxidative stress.

Main Methods:

• Transfection of adriamycin-sensitive L-M cells with an enTNF expression vector.
• Transfection of HeLa cells with an anti-sense TNF mRNA vector to inhibit enTNF synthesis.
• Assessment of adriamycin sensitivity, MnSOD activity, and expression of multidrug resistance genes (P-170, GST-pi, GSH).

Main Results:

• L-M cells overexpressing enTNF showed increased MnSOD levels and resistance to adriamycin.
• HeLa cells with inhibited enTNF synthesis exhibited suppressed MnSOD activity and enhanced adriamycin sensitivity.
• No changes in P-170 glycoprotein, glutathione S-transferase pi (GST-pi), or glutathione (GSH) levels were observed.

Conclusions:

• Endogenous TNF (enTNF) provides intracellular protection against adriamycin cytotoxicity.
• This protective effect is mediated by the induction of MnSOD, which scavenges reactive oxygen species.
• The mechanism is consistent with enTNF's protective role against exogenous TNF and heat stress.