MEDICAL HYPOTHESES AND RESEARCH
VOL. 1, No. 4, October 2004


J. Yu, et al.  [2004] Med Hypotheses Res 1: 267-274.


Precipitous Dose-Response Curves for the Anticancer
Actions of Microtubule-Disrupting Agents in Human
Breast Cancer Cells: Implications for High-Dose
Regimen in Anticancer Chemotherapy


Jina Yu, Zhi-Jian Liu, Gui-Zhen Han, Anthony J. Lee and
Bao Ting Zhu*

Department of Basic Pharmaceutical Sciences, College of Pharmacy, University of South
Carolina, Columbia, SC 29208, USA


Abstract.  Disruption of the normal functions of mitotic microtubules is a common
target of attack for many anticancer drugs. We report here our observations that several
well-known microtubule-disrupting agents (paclitaxel, vinblastine, vincristine, vinorelbine,
colchicine, and 2-methoxyestradiol) each had almost identical and unusually precipitous
dose-response curves for their inhibition of the growth of five human breast cancer cell
lines in culture. The cancer cell lines examined in the present study included three estrogen
receptor-positive cell lines (MCF-7, T-47D, and ZR-75-1) and two estrogen
receptor-negative cell lines (MDA-MB-231 and MBA-MB-435s). These observations led us
to suggest that for this class of anticancer agents, the use of adequately high doses, rather
than opting for lower and safer doses, should be considered for breast cancer patients in
order to assure effective anticancer activity. Otherwise, a cancer patient may face the
possibility of reaping far less therapeutic benefits as they would have if these agents are
given at relatively lower doses that may produce drug concentrations even slightly below
the maximally-effective levels. Further studies are needed to determine whether such a
precipitous dose-response relationship observed in vitro for paclitaxel, vinca alkaloids, and
2-methoxyestradiol is also seen in breast cancer patients.

*Address all correspondence to: Dr. B. T. Zhu, Department of Basic Pharmaceutical
Sciences, College of Pharmacy, University of South Carolina, Room 617 of Coker Life
Sciences Building, 700 Sumter Street, Columbia, SC 29208 (USA).
E-mail:
BTZhu@cop.sc.edu


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