Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 6/2004

01-06-2004 | Original Article

Synergistic effects of ICI 182,780 on the cytotoxicity of cisplatin in cervical carcinoma cell lines

Authors: Patricia García-López, Mauricio Rodríguez-Dorantes, Enrique Pérez-Cárdenas, Marco Cerbón, Alejandro Mohar-Betancourt

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2004

Login to get access

Abstract

Purpose

We investigated the ability of the novel pure antiestrogen ICI 182,780 to modulate the cytotoxic effects of cisplatin in several cervical cancer cell lines.

Methods

The effect of cisplatin alone and cisplatin combined with ICI 182,780 on cellular death was studied using an assay based on a tetrazolium dye (sodium 3′-[1-(phenylamino-carbonyl)-3,4-tetrazolium], XTT). Before and after treatment with ICI 182,780, expression of the estrogen and progesterone receptor genes were assessed by a reverse transcriptase polymerase chain reaction (RT-PCR). Cell-cycle modifications after combined treatment with cisplatin and ICI 182,780 were studied by flow cytometry.

Results

Analysis of the data by the isobologram method showed that the combination of ICI 182,780 and cisplatin produced a synergistic antiproliferative effect in cervical cancer cells. The effect of ICI 182,780 on the cytotoxicity of cisplatin could be mediated, at least partially, by inhibition of estrogen and progesterone gene expression and by arresting the cell cycle at the G2/M phase.

Conclusions

Our results suggest that ICI 182,780 can improve the efficacy of cisplatin in cancer cells and that this antihormonal drug therapy may be a useful candidate for further evaluation in combination with antineoplastic drugs, particularly cisplatin, in the treatment of cancer.
Literature
1.
Add S, Yates RA, Laight A (2002) A phase 1 trial to assess the pharmacology of the new oestrogen receptor antagonist fulvestran on the endometrium in healthy postmenopausal volunteers. Br J Cancer 87:1354CrossRefPubMed
2.
Benedetti PP, Greggi S, Scambia G (1991) High-dose cisplatin and bleomycin neoadjuvant chemotherapy plus radical surgery in locally advanced cervical carcinoma: a preliminary report. Gynecol Oncol 41:212PubMed
3.
Branham WS, Fishman R, Streck RD, Medlock KL, De George JJ, Sheehan DM (1996) ICI 182,780 inhibits endogenous estrogen-dependent rat uterine growth and tamoxifen-induced developmental toxicity. Biol Reprod 54:160PubMed
4.
Carmichael J, DeGraff WG, Gazdar AF, Minna JD, Mitchell JB (1987) Evaluation of tetrazolium based semiautomated colorimetric assay: assessment of chemosensitivity testing. Cancer Res 47:936PubMed
5.
Chan TW, Pollak M, Huynh H (2001) Inhibition of insulin-like growth factor signaling pathways in mammary gland by pure antiestrogen ICI 182,780. Clin Cancer Res 7:2545PubMed
6.
Chou TC (1998) Drug combination: from laboratory to practice. J Lab Clin Med 132:6PubMed
7.
Chou TC, Motzer RJ, Youzhi Tong, Bosl GJ (1994) Computerized quantitation of synergism and antagonism of taxol, topotecan, and cisplatin against human teratocarcinoma cell growth a rational approach to clinical protocol design. J Natl Cancer Inst 86:1517PubMed
8.
9.
DeFriend DJ, Howell A, Nicholson RI, Anderson E, Dowsett M, Mansel RE, Blamey RW, Bundred NJ, Robertson JF, Saunders C, et al (1994) Investigation of a new pure antiestrogen (ICI 182780) in women with primary breast cancer. Cancer Res 54:408PubMed
10.
De Vincenzo R, Scambia G, Benedetti PP, Fattorasi A, Bonanno G, Ferlinic C, Isola G, Pernisco S, Mancuso S (1996) Modulatory effects of tamoxifen and ICI 182, 780 on Adriamycin resistance in MCF-7 human breast cancer cells. Int J Cancer 68:340CrossRefPubMed
11.
Drucker L, Stackievicz R, Radnay J, Shapira H, Cohen I, Yarkoni S (2003) Tamoxifen enhances apoptotic effect of cisplatin on primary endometrial cell cultures. Anticancer Res 23:1549PubMed
12.
Fontanelli R, Spatti G, Raspagliesi F, Zunino F (1992) A preoperative single course of high-dose cisplatin and bleomycin with glutathione protection in bulky stage IB carcinoma of the cervix. Ann Oncol 3:117
13.
Friedrich M, Mink D, Villena-Heinsen C, Woll-Hermann A, Schmidt W (1998) Tamoxifen and proliferation of vaginal and cervical epithelium in postmenopausal women with breast cancer. Eur J Obstet Gynecol Reprod Biol 80:221CrossRefPubMed
14.
Gandara DR, Perez EA, Wiebe V, De Gregorio MW (1991) Cisplatin chemoprotection and rescue: pharmacological modulation of toxicity. Semin Oncol 18:49
15.
Hahnel R, Martin JD, Masters AM, Ratajezak KT, Twaddle E (1979) Estrogen receptors and blood hormone levels in cervical carcinoma and other gynecological tumors. Gynecol Oncol 8:226PubMed
16.
He Q, Liang CH, Lippard SJ (2000) Steroid hormones induce HMG1 overexpression and sensitize breast cancer cells to cisplatin and carboplatin. Proc Natl Acad Sci U S A 97:5768CrossRefPubMed
17.
18.
Hornback WB, Shen RN, Sutton GP, Shidnia H, Kaiser HE (1994) Synergistic cytotoxic and antitumor effects of irradiation and taxol on human HeLa cervix carcinoma and mouse B16 melanoma cells. In Vivo 8:819PubMed
19.
Howell A, DeFriend DJ, Robertson JF, Blamey RW, Anderson L, Anderson E, Sutcliffe FA, Walton P (1996) Pharmacokinetics, pharmacological and anti-tumour effects of the specific anti-oestrogen ICI 182,780 in women with advanced breast cancer. Br J Cancer 74:300PubMed
20.
Howell A, Osborne CK, Morris C, Wakeling AE (2000) ICI 182,780 (Faslodex): development of a novel, “pure” antiestrogen. Cancer 89:817CrossRefPubMed
21.
Huang JC, Zamble DB, Reardon JT, Lippard ST, Sancar A (1994) HMG-domain proteins specifically inhibit the repair of the major DNA adduct of the anticancer drug cisplatin by human excision nuclease. Proc Natl Acad Sci U S A 91:10394PubMed
22.
Huynh H, Nickerson T, Pollak M, Yang X (1996) Regulation of insulin-like growth factor I receptor expression by the pure antiestrogen ICI 182,780. Clin Cancer Res 2:2037PubMed
23.
Hwang JY, Lin BY, Tang FM, Yu WC (1992) Tamoxifen stimulates human papillomavirus type 16 gene expression and cell proliferation in a cervical cancer cell line. Cancer Res 52:6848PubMed
24.
Hyder S, Chiappetta C, Murthy L, Stancel G (1997) Selective inhibition of estrogen-regulated gene expression in vivo by the pure antiestrogen ICI 182,780. Cancer Res 57:2547PubMed
25.
Lackey BR, Gray SL, Henricks DM (2000) Synergistic approach to cancer therapy: exploiting interactions between anti-estrogens, retinoids, monoterpenes and tyrosine kinase inhibitors. Med Hypotheses 54:832CrossRefPubMed
26.
Loehrer PJ, Einhorn LH (1984) Cisplatin, diagnosis and treatment. Ann Intern Med 100:704PubMed
27.
Marino M, Acconcia F, Bresciani F, Weisz A, Trentalance A (2002) Distinct nongenomic signal transduction pathways controlled by 17B-estradiol regulate DNA synthesis and cyclin D1 gene transcription in HepG2 cells. Mol Biol Cell 13:3720CrossRefPubMed
28.
Mourits MJ, Hollema H, De Vries EG, Ten-Hoor KA, Willemse PH, VanDer Zee AG (2002) Apoptosis and apoptosis-associated parameters in relation to tamoxifen exposure in postmenopausal endometrium. Hum Pathol 33:341CrossRefPubMed
29.
Nooter K, Stoter G (1996) Molecular mechanisms of multidrug resistance in cancer chemotherapy. Pathol Res Pract 192:768PubMed
30.
Ozols RF (1995) Current status of chemotherapy for ovarian cancer. Semin Oncol 22:61
31.
Perez EA, Gandara DR, Edelman MJ, O’Donnell R, Lauder IJ, DeGregorio M (2003) Phase I trial of high-dose tamoxifen in combination with cisplatin in patients with lung cancer and other advanced malignancies. Cancer Invest 21:1CrossRefPubMed
32.
Rosenberg Zand RS, Grass L, Magklara A, Jenkins DJ, Diamandis EP (2000) Is ICI 182,780 an antiprogestin in addition to being an antiestrogen?. Breast Cancer Res Treat 60:1CrossRefPubMed
33.
Sacks PG, Haris D, Chou TC (1995) Modulation of growth and proliferation in squamous cell carcinoma by retinoic acid: a rationale for combination therapy. Int J Cancer 61:409PubMed
34.
Soutter WP, Leake RA (1987) Steroid hormone receptors in gynaecological cancer. In: Bonnard J (ed) Recent advances in obstetrics and gynaecology. Churchill Livingstone, Edinburgh, p 175
35.
Tan-Chiu E, Wang J, Costantino JP, Paik S, Butch C, Wickerham DL, Fisher B, Wolmark N (2003) Effects of tamoxifen on benign breast disease in women at high risk for breast cancer. J Natl Cancer Inst 95:302CrossRefPubMed
36.
Tavassoli M, Soltaninia J, Rudnicka J, Mashanyare D, Johnson N, Gaken J (2002) Tamoxifen inhibits the growth of head and neck cancer cells and sensitizes these cells to cisplatin induced apoptosis: role of TGF-beta1. Carcinogenesis 23:1569CrossRefPubMed
37.
Thomas EJ, Walton P, Thomas NM, Dowsett M (1994) The effects of ICI 182,780, a pure anti-estrogen, on the hypothalamic-pituitary-gonadal axis and on endometrial proliferation in pre-menopausal women. Hum Reprod 9:1991PubMed
38.
Vargas-Roid LM, Lotfi H, Olcese JE, Lo-Castro G, Ciocca DR (1993) Effects of short-term tamoxifen administration in patients with invasive cervical carcinoma. Anticancer Res 13:2457PubMed
Metadata
Title
Synergistic effects of ICI 182,780 on the cytotoxicity of cisplatin in cervical carcinoma cell lines
Authors
Patricia García-López
Mauricio Rodríguez-Dorantes
Enrique Pérez-Cárdenas
Marco Cerbón
Alejandro Mohar-Betancourt
Publication date
01-06-2004
Publisher
Springer-Verlag
Published in
Cancer Chemotherapy and Pharmacology / Issue 6/2004
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-003-0760-3

Other articles of this Issue 6/2004

Cancer Chemotherapy and Pharmacology 6/2004 Go to the issue

Original Article

Plasma and cerebrospinal fluid pharmacokinetic study of BNP1350 in nonhuman primates

Original Article

The effects of degree of hepatic or renal impairment on the pharmacokinetics of exemestane in postmenopausal women

Original Article

Population pharmacokinetics of melphalan, infused over a 24-hour period, in patients with advanced malignancies

Original Article

Phase I and pharmacokinetic study of the farnesyltransferase inhibitor R115777 in combination with irinotecan in patients with advanced cancer

Original Article

A multicenter phase II study of cisplatin and docetaxel (Taxotere) in the first-line treatment of advanced ovarian cancer: a GINECO study

Original Article

Dexamethasone as a chemoprotectant in cancer chemotherapy: hematoprotective effects and altered pharmacokinetics and tissue distribution of carboplatin and gemcitabine
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits