Journal Article

Growth inhibitory effects of diallyl disulfide on human breast cancer cell lines

Hiroyuki Nakagawa, Koji Tsuta, Katsuji Kiuchi, Hideto Senzaki, Kanji Tanaka, Koshiro Hioki and Airo Tsubura

in Carcinogenesis

Volume 22, issue 6, pages 891-897
Published in print June 2001 | ISSN: 0143-3334
Published online June 2001 | e-ISSN: 1460-2180 | DOI:
Growth inhibitory effects of diallyl disulfide on human breast cancer cell lines

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Diallyl disulfide (DADS) is an oil-soluble organosulfur compound found in garlic. The effect of synthetic DADS on the growth of estrogen receptor (ER)-positive (KPL-1 and MCF-7) and -negative (MDA-MB-231 and MKL-F) human breast cancer cell lines was examined. In an in vitro MTT assay, regardless of ER status, DADS at an IC50 of 1.8–18.1 μM after 72 h incubation caused inhibition of growth in all four cell lines examined. Growth inhibition was due to apoptosis as seen by the appearance of a sub G1 fraction. In MDA-MB-231 cells, the apoptosis cascade comprised up-regulation of Bax protein (142%), down-regulation of Bcl-XL protein (38%) and activation of caspase-3 (438%) compared with controls. In an in vivo assay by orthotopic (right thoracic mammary fat pad) transplantation of KPL-1 cells in female nude mice, intraperitoneal injection of 1 or 2 mg DADS three times a week from the day of tumor cell inoculation until the end of the experiment (after 35 days) caused growth retardation and 43% reductions in primary tumor weight, respectively, compared with DADS-untreated mice without apparent side effects. Cell proliferation as evaluated by proliferating cell nuclear antigen (PCNA)-labeling in transplanted tumor of DADS-untreated mice was 59.6%, and 1 and 2 mg DADS-treated mice was 44.6 and 44.5%, respectively. In MDA-MB-231 cells, DADS antagonized the effect of linoleic acid (LA), a potent breast cancer cell stimulator (at DADS = 1.8 μM and LA ≥ 6.5×102 μM concentration), and synergized the effect of eicosapentaenoic acid (EPA), a potent breast cancer cell suppressor (at DADS >3 × 10–3 μM and EPA > 6.3 × 10–1 μM concentration). Thus, DADS could be a promising anticancer agent for both hormone-dependent and -independent breast cancers, and may harmonize with polyunsaturated fatty acids known as modulators of breast cancer cell growth.

Keywords: CI, combination index; DADS, diallyl disulfide; DMBA, 7,12-dimethylbenz[α]anthracene; DMEM, Dulbecco's modified Eagle's minimum essential medium; DMSO, dimethylsulfoxide; EPA, eicosapentaenoic acid; ER, estrogen receptor; FBS, fetal bovine serum; IC50, 50% inhibitory concentration; LA, linoleic acid; MNU, N-methyl-N-nitrosourea; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; PBS, phosphate buffered saline; PCNA, proliferating cell nuclear antigen; PhIP, 2-amino-1-methyl-6-phenylimidazo-4,5-b-pyridine; PUFA, polyunsaturated fatty acid; TUNEL, TdT-mediated dUTP-digoxigenin nick end-labeling.

Journal Article.  5417 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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