Background:

Chlorambucil is an alkylating agent with antitumor activity.
Chlorambucil can deprive the function of complementary strands of DNA molecules via alkalization-induced cross interaction, and then inhibits tumor cell proliferation. Chlorambucil (0, 2.5, 5, 10 μM) exhibits slight inhibitory effect on Raji cell apoptosis, but potently increases DR4 and DR5 mRNA expression in Raji cells. Chlorambucil (10 μM) in combination with Tumor necrosis factor (TNF) related apoptosis inducing ligand (TRAIL, 80 ng/ml) has synergistic effect on Raji cell apoptosis and inhibition on proliferation[1].
Chlorambucil (0.2 mg/kg, p.o.) in combination with levamisole (5 mg/kg) has enhanced anti-cancer effect on Ehrlich ascites carcinoma which elevates apoptosis of Ehrlich ascites carcinoma and the survival rate of the mice. However, Chlorambucil exhibits adverse effects on the liver and kidneys of mice[2].
Reference:
[1]. Guo JX, et al. Synergistic effects of chlorambucil and TRAIL on apoptosis and proliferation of Raji cells. Eur Rev Med Pharmacol Sci. 2017 Oct;21(20):4703-4710.
[2]. Salem FS, et al. Biochemical and pathological studies on the effects of levamisole and chlorambucil on Ehrlich ascites carcinoma-bearing mice. Vet Ital. 2011 Jan-Mar;47(1):89-95.