Effect of withaferin a on Ehrlich ascites tumor cells. II. Target tumor cell destruction in vivo by immune activation

AbstractIntraperitoneal administration of Withaferin A 24 h after inoculation of Ehrlich ascites carcinoma resulted in an immediate inhibition of tumor growth, followed by complete disappearance of the malignant cells after 3‐4 days. During this period a striking proliferation of macrophages in the peritoneal cavity and clustering of viable acid‐phosphatase‐rich macrophages around Ehrlich ascites tumor cells was observed. In addition, giant cell formation in the peritoneal cavity of the tumor‐rejecting mice was commonly seen. No significant difference was found in the number of lymphocytes and polymorphonuclears of the peritoneal exudate of the tumor‐rejecting mice as compared to untreated tumor‐bearing mice. A similar sequence of changes with an even more striking proliferation of macrophages terminating again in complete tumor regression was observed after reinoculation of Ehrlich ascites cells to Withaferin A cured mice. Growth of Ehrlich ascites tumor cells in normal mice was prevented by passive transfer of serum or peritoneal cells, but not by spleen cells taken from immune mice. Humoral antibodies in the serum of immune mice were demonstrated by the complement fixation, the passive cutaneous anaphylaxis, and the cytotoxic tests. One‐day‐old suckling litters born to immune mothers were also refractory to Ehrlich ascites implantation. However, Ehrlich ascites cell growth was not affected if the litters were injected previously with a cell‐free tumor homogenate.