Full Journal - Journal of Cell and Molecular Biology - Haliç Üniversitesi

84 Mehmet Topçul et al.
Now, 106 years after Beatson’s pioneering work
with oophorectomy, endocrine therapy has been
shown to have a major role in the adjuvant setting.
Hormonal therapy may eventually prove to have its
greatest impact in breast cancer preventation.
Newer hormonal agents, especially the
antiestrogens, have opened up additional doors for
trials of endocrine therapy (Muss, 1992).
Epirubicin, an anthracycline antibiotic, inhibits
DNA replication and transcription by intercalation
between DNA strands which are the ultimate
intracellular target of anthracyclines (Aglietta et al.,
1993; Mouridsen, 1992).
Cell culture studies exhibit epirubicin enters the
cells rapidly is localized in nuclei and inhibits nucleic
acid synthesis and cell division (Robert and Gianni,
1993).
In vitro studies showed that epirubicin has
maximal cytotoxic effects in the S and G2 phases
(Greg, 1993).
Although the precise mechanism of epirubicin is
not fully understood, performed studies suggest that it
forms a complex with DNA by intercalation between
DNA strands, thus inhibiting DNA replication and
transcription (Sinha and Porti, 1990; Skladanowski
and Konopa, 1994).
Epirubicin has been shown to be cytotoxic, with
an increase in both the degree and rate of induction of
DNA strand breakage (Cantoni et al., 1990).
Adding tamoxifen to epirubicin treatment induced
S phase arrest in FM3A cells. In the majority of trials,
chemotherapy combined with endocrine therapy has
given improved results compared with chemotherapy
alone (Boccardo et al., 1990; Mouridsen, 1992).
Thus, the results of our study seem to be
concordant with the above mentioned studies,
suggesting that combinations of drugs are superior to
single agents.
As a result, we think that in this experiments,
some interactions between cytotoxic agents and
tamoxifen is synergistic and additive.
In ER-positive and ER-negative breast cancer cell
lines, the growth, cytotoxic, and cell-cycle effects
must be examined and compared.
References
Aglietta M, Monzeglio C, Pasquino P, Carnino F, Stern AC
and Gavosto F. Short-term administration of
granulocyte-macrophage colony stimulating factor
decreases hematopoietic toxicity of cytostatic drugs.
Cancer. 72: 2970-2973, 1993.
Beatson GT. On the treatment of inoperable cases of
carsinoma of mammal: Suggestions for a new method
of treatment, with illustrative cases. Lancet. 2: 104-
107, 1896.
Boccardo F, Rubagotti A, Bruzzi P, Cappellini M, Isola G,
Nenci I, Piffanelli A, Scanni A, Sismondi P and Santi L.
Chemotherapy versus tamoxifen versus chemotherapy
plus tamoxifen in node-positive, estrogen receptorpositive
breast cancer patients: Results of a
multicentric Italian study. J Clin Oncol. 8: 1310-
1320, 1990.
Cantoni O, Sestili P, Cattabeni F, Geroni C and Giuliani F.
Comparative effects of doxorubicin and 4´epidoxorubicin
on nucleic acid metabolism and
cytotoxicity in a human tumour cell line. Cancer
Chemotherapy and Pharmacology. 27: 47-51, 1990.
Clarke RB, Laidlaw IJ, Jones LJ, Howell A and Anderson E.
Effect of tamoxifen on Ki67 labelling index in human
breast tumours and it’s relationship to oestrogen
progesterone receptor status. Br J Cancer. 67: 606-
11, 1993.
Cuzick J and Baum M. Tamoxifen and contralateral breast
cancer. Lancet (i). 282, 1985.
Di marco A. Epirubicin: Mechanism of action at the
cellular level. In: Advances in Anthracycline
Chemotherapy. Epirubicin. Bonadonna G (Ed). Masson,
Milano - Italia. 41-47, 1984.
Douglas KT. Anticancer drugs, DNA-intercalation and free
radical attack. Chemistry and Industry. 766-771, 1984.
Greg L, Faulds P and Faulds D. Epirubicin. A review of its
pharmacodynamic and pharmacokinetic properties, and
therapeutic use in cancer chemotherapy. Drugs.
45: 788-856, 1993.
Gullino PM, Pettigrew HN and Grantham FH. N-
Nitrosomethylurea as mammary gland carcinogen in
rats. J Natl Cancer Inst. 54: 401-414, 1975.
Huggins SC, Grand LC and Brillantes FP. Mammary
cancer, induced by a single feeding of polynuclear
hydrocarbons and their suppression. Nature. 189: 204-
207, 1962.
Lippman M and Huff KA. Demonstration of androgen and
estrogen receptors in a human breast cancer using a
new protamine sulfate assay. Cancer. 38: 868-874,
1976.
Mc Guire WL, Horwitz KB, Zava DT, Garola RE and
Chamness GC. Hormones in breast cancer: Update
1978. Metabolism. 27: 487-501, 1978.
Mouridsen H, Palshof T, Paterson J and Battersby L.
Tamoxifen in advanced breast cancer. Cancer Treat
Rev. 5: 131-141, 1978.
Mouridsen HT. Systemic therapy of advanced breast
cancer. Drugs. 44 Suppl 4: 17-28, 1992.