Abstract
We report here on the antineoplastic, toxicologic, and transmembrane transfer properties of vanadocene dichloride (VDC), a representative metallocene dihalide. VDC is cytotoxic to HEp-2 human epidermoid carcinoma cells, in vitro, in a dose dependent manner, with a Do value (dose increment reducing the survival fraction by 1/e) of 0.530 ± 0.005 μg/ml. Under similar experimental conditions, the Do for cisplatin (CDDP) against these cells is 0.46 ± 0.08 μg/ml. In a murine mammary adenocarcinoma (TA3Ha) system, 125 μg/ml VDC inhibits the tumor-forming ability of 105 cells upon i.p. inoculation into syngeneic Strain A mice. The transmembrane transfer rate constants for the metal uptake of VDC and CDDP by TA3Ha cells in vitro were found to be 3.3 ± 0.8 × 10-4 min-1 and 12 ± 2.0 × 10t-4 min-1, respectively. In vivo studies with TA3Ha cells show that two i.p. treatments of 20, 40, and 60 mg/kg VDC increase the host survival by 30, 50, and 90%, respectively. Under similar conditions, 2, 4, and 6 mg/kg CDDP (equitoxic dose levels) prolong the host survival 50, 75, and 83%, respectively. Morphological, blood urea nitrogen level, and serum creatinine level data for Strain A mice treated with 60 mg/kg VDC give no evidence of renal or small intestinal damage. However, changes in the liver consistent with fatty cell degeneration are observed in these mice.
| Original language | English |
|---|---|
| Pages (from-to) | 117-124 |
| Number of pages | 8 |
| Journal | Inorganica Chimica Acta |
| Volume | 152 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 1988 |
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ASJC Scopus subject areas
- Biochemistry
- Inorganic Chemistry
- Physical and Theoretical Chemistry
- Materials Chemistry
- Medicine(all)
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Antitumor and toxicologic properties of the organometallic anticancer agent vanadocene dichloride. / Murthy, M. Satya; Rao, Leela N.; Kuo, Louis Y.; Toney, Jeffrey H.; Marks, Tobin J.
In: Inorganica Chimica Acta, Vol. 152, No. 2, 1988, p. 117-124.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antitumor and toxicologic properties of the organometallic anticancer agent vanadocene dichloride
AU - Murthy, M. Satya
AU - Rao, Leela N.
AU - Kuo, Louis Y.
AU - Toney, Jeffrey H.
AU - Marks, Tobin J
PY - 1988
Y1 - 1988
N2 - We report here on the antineoplastic, toxicologic, and transmembrane transfer properties of vanadocene dichloride (VDC), a representative metallocene dihalide. VDC is cytotoxic to HEp-2 human epidermoid carcinoma cells, in vitro, in a dose dependent manner, with a Do value (dose increment reducing the survival fraction by 1/e) of 0.530 ± 0.005 μg/ml. Under similar experimental conditions, the Do for cisplatin (CDDP) against these cells is 0.46 ± 0.08 μg/ml. In a murine mammary adenocarcinoma (TA3Ha) system, 125 μg/ml VDC inhibits the tumor-forming ability of 105 cells upon i.p. inoculation into syngeneic Strain A mice. The transmembrane transfer rate constants for the metal uptake of VDC and CDDP by TA3Ha cells in vitro were found to be 3.3 ± 0.8 × 10-4 min-1 and 12 ± 2.0 × 10t-4 min-1, respectively. In vivo studies with TA3Ha cells show that two i.p. treatments of 20, 40, and 60 mg/kg VDC increase the host survival by 30, 50, and 90%, respectively. Under similar conditions, 2, 4, and 6 mg/kg CDDP (equitoxic dose levels) prolong the host survival 50, 75, and 83%, respectively. Morphological, blood urea nitrogen level, and serum creatinine level data for Strain A mice treated with 60 mg/kg VDC give no evidence of renal or small intestinal damage. However, changes in the liver consistent with fatty cell degeneration are observed in these mice.
AB - We report here on the antineoplastic, toxicologic, and transmembrane transfer properties of vanadocene dichloride (VDC), a representative metallocene dihalide. VDC is cytotoxic to HEp-2 human epidermoid carcinoma cells, in vitro, in a dose dependent manner, with a Do value (dose increment reducing the survival fraction by 1/e) of 0.530 ± 0.005 μg/ml. Under similar experimental conditions, the Do for cisplatin (CDDP) against these cells is 0.46 ± 0.08 μg/ml. In a murine mammary adenocarcinoma (TA3Ha) system, 125 μg/ml VDC inhibits the tumor-forming ability of 105 cells upon i.p. inoculation into syngeneic Strain A mice. The transmembrane transfer rate constants for the metal uptake of VDC and CDDP by TA3Ha cells in vitro were found to be 3.3 ± 0.8 × 10-4 min-1 and 12 ± 2.0 × 10t-4 min-1, respectively. In vivo studies with TA3Ha cells show that two i.p. treatments of 20, 40, and 60 mg/kg VDC increase the host survival by 30, 50, and 90%, respectively. Under similar conditions, 2, 4, and 6 mg/kg CDDP (equitoxic dose levels) prolong the host survival 50, 75, and 83%, respectively. Morphological, blood urea nitrogen level, and serum creatinine level data for Strain A mice treated with 60 mg/kg VDC give no evidence of renal or small intestinal damage. However, changes in the liver consistent with fatty cell degeneration are observed in these mice.
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U2 - 10.1016/S0020-1693(00)83343-5
DO - 10.1016/S0020-1693(00)83343-5
M3 - Article
VL - 152
SP - 117
EP - 124
JO - Inorganica Chimica Acta
JF - Inorganica Chimica Acta
SN - 0020-1693
IS - 2
ER -