Rhodium (II) Butyrate: A Potential Anticancer Drug With Cell Cycle Phase-Specific Effects in HeLa Cells2

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Abstract
Rhodium (II) carboxylate complexes possess significant carclnostatlc activity against a wide range of mouse tumors. The effects of the most potent rhodium (II) compound, rhodium (II) butyrate, on the survival, cycle kinetics, and chromosome structure of HeLa cells were evaluated. This compound was found to be extremely cytotoxic at relatively low concentrations. The survival curves for HeLa cells treated with rhodium (II) butyrate showed dose- and duration-dependent responses, with a prominent shoulder generally seen in X-irradiated cells. HeLa cells continuously exposed to 0.4 μ M rhodium (II) butyrate were significantly retarded in their cycle traverse. The retardation of cell cycle progression appeared to be due to the inhibitory effects of this drug on DNA and protein syntheses. Maximum inhibition was seen in DNA synthesis, whereas RNA synthesis was unaffected. Some increase in the frequency of chromatid gaps and breaks, but not chromosome rearrangements or sister chromatid exchanges, was observed in drug-treated cells. With regard to survival, S-phase cells were most sensitive to this drug, whereas G1 phase, G2 phase, and mitotic cells were equally less sensitive. Noncycling plateau-phase cells were insensitive to this drug treatment. These studies revealed that DNA is not the primary target for the action of rhodium (II) butyrate, but its major effect, inhibition of DNA synthesis, is probably mediated through the inhibition of enzyme(s) involved in DNA synthesis, which might contain catalytically essential sulfhydryl groups. Rhodium (II) complexes have been shown to inhibit preferentially enzymes with sulfhydryl groups in or near the active site.

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