title: CHML suppresses cell growth and induces apoptosis in multiple human tumor lines.
abstract: 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.
authors.affiliation: Department of Radiation Oncology, Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, PA 15213, USA.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhan
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D015689:Oncogene Protein p21(ras) / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D019253:Proto-Oncogene Proteins c-bcl-2; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000502:physiology; D014815:Vitamins / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D005231:Fatty Acids, Unsaturated; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014815:Vitamins; D051028:bcl-2-Associated X Protein; C403743:cytotropic heterogeneous molecular lipid; D015689:Oncogene Protein p21(ras)