Programmed cell death in 2',3'-dideoxycytidine-resistant human monoblastoid U937 cells

Area of Science:

• Virology
• Cell Biology
• Biochemistry

Background:

• 2',3'-Dideoxycytidine is an in vitro inhibitor of human immunodeficiency virus (HIV) used in acquired immunodeficiency syndrome treatment.
• Long-term exposure to this drug selects for drug-resistant U937 monoblastoid cells (U937-R).
• Previous studies indicated higher basal respiration, protein kinase C activity, superoxide anion release, and reduced glutathione in U937-R cells.

Purpose of the Study:

• To evaluate the differential susceptibility of U937-R and parental U937 cells to apoptosis induction.
• To investigate the role of protein kinase C and glutathione in drug resistance and apoptosis.
• To compare the apoptotic response to staurosporine, okadaic acid, and SIN-1 treatments.

Main Methods:

• Treatment of U937 and U937-R cells with staurosporine, okadaic acid, and SIN-1.
• Analysis of apoptosis using light and electron microscopy.
• Agarose gel electrophoresis of isolated DNA to detect apoptotic features.

Main Results:

• U937-R cells displayed more advanced apoptotic features than parental cells after staurosporine treatment.
• Okadaic acid did not induce differential apoptotic behavior between the two cell lines.
• SIN-1 treatment resulted in an increased number of apoptotic cells in the parental U937 line compared to U937-R cells.

Conclusions:

• The U937-R cell line exhibits distinct responses to apoptosis-inducing agents.
• Elevated protein kinase C and glutathione levels in U937-R cells may contribute to their resistance to programmed cell death.
• These findings suggest complex mechanisms underlying drug resistance in HIV-infected cells.