In the present study, we have investigated the effect of
cytotropic heterogeneous molecular lipid (
CHML), a new
anticancer agent, on growth suppression in a variety of human tumor cell lines. At a non-toxic concentration (a range from 25 micrograms/ml to 100 micrograms/ml),
CHML has shown to strongly inhibit
tumor cell growth by using a typical colony survival assay. At a treatment of concentration of 50 micrograms/ml for 6 hours,
CHML is able to suppress 50% of the
tumor cell colony formation. At a concentration of 100 micrograms/ml (the therapeutic dosage in the clinical trial), more than 90% of the cells were killed in human
breast carcinoma MCF-7,
colorectal carcinoma RKO, kidney
carcinoma G410, lung
carcinoma and human
myeloid leukemia ML-1 lines. In contrast, growth suppression of non-cancerous human skin fibroblasts by
CHML was observed much less than that seen in
tumor lines. These results indicate that
CHML is an efficient inhibiting agent in
tumor cell growth and is able to generate greater suppression in
tumor cells than in noncancerous cells. With the use of DNA fragmentation assay,
CHML was found to induce apoptosis in MCF-7, ML-1, H1299 and RKO lines
after treatment at a concentration of 75 micrograms/ml for 8 hours. Following the
CHML treatment, the
tumor suppressor p53
protein elevated in RKO cells at 2 h posttreatment. The induction of p53 reached a peak at 4 hr and returned to normal level 16 hr later. Consistent with this result, Bax, which is regulated by p53 and is able to promote apoptosis, was also found to increase in a same kinetic manner as p53. These results suggest that the p53-pathway is activated by
CHML and the activation of p53 may contribute to
CHML-induced apoptosis in some
tumor cells, such as MCF-7, RKO and ML-1. Considering that
CHML is able to induce apoptosis in H1299 cells, which are of p53-negative status, it is speculated that
CHML induces programmed cell death through both the p53-dependent and- independent pathways.