Inhibition of cancer cell growth by ruthenium complexes.

Abstract

BACKGROUND:

Previous studies suggest that certain transition metal complexes, such as cisplatin, are efficacious for treating various cancer types, including ovarian, lung, and breast.

METHODS:

In order to further evaluate ruthenium (Ru) complexes as potential anti-cancer agents, we synthesized and evaluated Ru-arene complexes. Two complexes with the general formula [Ru (η (6)-p-cym) (N-N) Cl](+) were tested for their abilities to inhibit cancer cells.

RESULTS:

The complex with o-phenylenediamine as the N-N ligand (o-PDA) significantly inhibited growth of breast (MDA-MB-231, MCF-7, SKBR-3, and SUM149), lymphoma (Raji), melanoma (Bowes), and osteosarcoma (HT1080); however, the complex with o-benzoquinonediimine (o-BQDI) was ineffective except for SUM149. In contrast, o-PDA failed to inhibit growth of human breast epithelial cells, MCF-10A. Treatment of MDA-MBA-231 cells with o-PDA resulted in a significant reduction of productions of PDGF-AA, GM-CSF, and VEGF-A proteins at the transcriptional levels. Finally, we demonstrated that o-PDA synergistically inhibited MDA-MB-231 cell growth with cyclophosphamide but not doxorubicin or paclitaxel.

CONCLUSION:

These results suggest that Ru-arene complexes are promising anti-cancer drugs that inhibit progression and metastasis by blocking multiple processes for breast and other types of cancer.

• Authors: Joji Iida, Elisabeth T Bell-Loncella, Marc L Purazo, Yifeng Lu, Jesse Dorchak, Rebecca Clancy, Julianna Slavik, Mary Lou Cutler, Craig D Shriver
• Journal: Journal of translational medicine (J Transl Med) Vol. 14 Pg. 48 (Feb 12 2016) ISSN: 1479-5876 [Electronic] England
• PMID: 26867596 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antineoplastic Agents
• Coordination Complexes
• Intercellular Signaling Peptides and Proteins
• Phenylenediamines
• Ruthenium
• 1,2-diaminobenzene

Topics

• Antineoplastic Agents (pharmacology, therapeutic use)
• Breast Neoplasms (drug therapy, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Coordination Complexes (chemistry, pharmacology, therapeutic use)
• Female
• Humans
• Intercellular Signaling Peptides and Proteins (biosynthesis)
• Phenylenediamines (pharmacology)
• Ruthenium (chemistry, pharmacology, therapeutic use)