Chlorophyllin protects cells from the cytostatic and cytotoxic effects of quinacrine mustard but not of nitrogen mustard.
Chlorophyllin (CHL), the sodium and copper salt of chlorophyll, is capable of inhibiting the mutagenic activity of many chemical compounds. Several mechanisms have been advanced to explain the antimutagenic activity of CHL, including its antioxidant properties and its ability to form complexes with mutagens. The present study was designed to reveal whether the heterocyclic aromatic nature of a potential mutagen is essential to its sensitivity to CHL. Toward this end, the inhibitory effect of CHL on two compounds of similar chemical reactivity (mustards), that either embodied an aromatic structure (quinacrine mustard; QM) or did not (nitrogen mustard; NM), were compared. Human leukemic HL-60 and breast carcinoma MCF-7 cells were treated with QM or NM in the absence or presence of various concentrations of CHL. Both QM and NM when administered for 1-2 h at micromolar concentrations exerted similar effects; both arrested cells in G2 phase of the cell cycle, induced apoptosis and reduced the clonogenicity of MCF-7 cells. The simultaneous addition of 0.22 M CHL to cultures receiving QM virtually abolished the QM-induced inhibition of cell growth and clonogenicity. In contrast, CHL had no effect on reducing the cytostatic or cytotoxic activity of NM. CHL alone, at a concentration of 0.22 M, had minimal effect on growth of HL-60 cells slightly perturbing their progression through G2. The results are consistent with the model that explains the inhibition of the activity of mutagens or antitumor drugs with aromatic structures by CHL as mediated by its ability to sequester these molecules within heterologous mutagen:CHL complexes that are maintained by stacking interactions. Therefore, excess of chlorophyll in the diet, by sequestering aromatic mutagens (or antitumor drugs with a heterocyclic structure, if taken orally), may inhibit their accessibility to cells, thereby reducing their activity.
Brander Cancer Research Institute at New York Medical College, 19 Bradhurst Avenue, Suite 2400, Hawthorne, NY 10532, USA.
B
B
Ardelt
J
J
Kunicki
F
F
Traganos
Z
Z
Darzynkiewicz
D016587:Antimutagenic Agents / Q000494:pharmacology*; D018906:Antineoplastic Agents, Alkylating / Q000633:toxicity*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002735:Chlorophyllides / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004338:Drug Combinations; D005434:Flow Cytometry; D006801:Humans; D007700:Kinetics; D008466:Mechlorethamine / Q000633:toxicity*; D011797:Quinacrine Mustard / Q000633:toxicity*; D013997:Time Factors; D014407:Tumor Cells, Cultured / Q000187:drug effects
D016587:Antimutagenic Agents; D018906:Antineoplastic Agents, Alkylating; D002735:Chlorophyllides; D004338:Drug Combinations; D011797:Quinacrine Mustard; D008466:Mechlorethamine; C007020:chlorophyllin