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

Abstract

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 IC(50) of 1.8-18.1 microM 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-X(L) 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 microM and LA > or = 6.5x10(2) microM concentration), and synergized the effect of eicosapentaenoic acid (EPA), a potent breast cancer cell suppressor (at DADS >3 x 10(-3) microM and EPA > 6.3 x 10(-1) microM 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.

• Authors: H Nakagawa, K Tsuta, K Kiuchi, H Senzaki, K Tanaka, K Hioki, A Tsubura
• Journal: Carcinogenesis (Carcinogenesis) Vol. 22 Issue 6 Pg. 891-7 (Jun 2001) ISSN: 0143-3334 [Print] England
• PMID: 11375895 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allyl Compounds
• Antineoplastic Agents
• Arachidonic Acids
• Disulfides
• Growth Inhibitors
• Receptors, Estrogen
• diallyl disulfide
• Linoleic Acid

Topics

• Allyl Compounds (pharmacology)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects, physiology)
• Arachidonic Acids (pharmacology)
• Breast Neoplasms (drug therapy, pathology)
• Cell Division (drug effects)
• Diet
• Disulfides (pharmacology)
• Drug Synergism
• Female
• Flow Cytometry
• Growth Inhibitors (pharmacology)
• Humans
• Inhibitory Concentration 50
• Linoleic Acid (antagonists & inhibitors, pharmacology)
• Lymphatic Metastasis
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Receptors, Estrogen (physiology)
• Tumor Cells, Cultured
• Xenograft Model Antitumor Assays