Apoptosis

, Volume 7, Issue 1, pp 49–57 | Cite as

Protein A-activated macrophages induce apoptosis in Ehrlich's ascites carcinoma through a nitric oxide-dependent pathway

  • S. Chattopadhyay
  • T. Das
  • G. Sa
  • P. K. Ray
Article

Abstract

Protein A (PA) of Staphylococcus aureus has been demonstrated to possess anti-tumor activity against a wide variety of tumors. In the current study we endeavored to obtain a mechanistic insight into PA-mediated Ehrlich's ascites carcinoma (EAC) killing. Our results indicate that PA stimulates generation of nitric oxide (NO) from murine peritoneal macrophages. Nitric oxide in turn induces cytotoxic damage to the tumor cells. Analysis of the morphological features and cell cycle phase distribution pattern of nuclear DNA revealed an induction of apoptosis (appearance of sub-G0/G1 population) in EAC after PA treatment. We have further elaborated the alterations in the expressions of the proto-oncoproteins p53 and Bax, together with a change in the ratio of Bcl-2/Bax in the treated tumor cells, which favor apoptosis. PA-induced apoptosis and changes in the expression of oncoproteins in the tumor cells was prevented by the suppression of NO release by the addition of L-NAME, the competitive NOS inhibitor, suggesting a possible mechanism by which PA exerts its anti-tumor activities involving nitric oxide through the alteration in the expressions of pro-apoptotic proteins.

apoptosis Bax nitric oxide p53 protein A tumor 

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Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • S. Chattopadhyay
    • 1
  • T. Das
    • 1
  • G. Sa
    • 1
  • P. K. Ray
    • 2
  1. 1.Animal Physiology SectionBose InstituteCalcuttaIndia
  2. 2.St. Luke's Roosevelt Health Sciences Center, Surgical Oncology Program, Beth Israel Medical CenterAlbert Einstein College of MedicineNew YorkUSA

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