Conventional chemotherapy is mostly effective in the treatment of rapidly-dividing differentiated tumor cells but has limited application toward eliminating cancer stem cell (CSC) population. The presence of a very small number of CSCs may contribute to the development of therapeutic resistance, metastases, and relapse. Thus, treatment failure by developing novel anticancer drugs capable of effective targeting of CSCs is at present a major challenge for research focused on chemotherapy of cancer. Here, we show that Os(II) complex 2 [Os(η6-pcym)(bphen)(dca)]PF6 (pcym = p-cymene, bphen = bathophenanthroline, and dca = dichloroacetate), is capable of efficient and selective killing CSCs in heterogeneous populations of human breast cancer cells MCF-7 and SKBR-3. Notably, its remarkable submicromolar potency to kill CSCs is considerably higher than that of its Ru analog, [Ru(η6-pcym)(bphen)(dca)]PF6 (complex 1) and salinomycin, one of the most selective CSC-targeting compounds hitherto identified. Furthermore, Os(II) complex 2 reduces the formation, size, and viability of three-dimensional mammospheres which more closely reflect the tumor microenvironment than cells in traditional two-dimensional cultures. The antiproliferation studies and propidium iodide staining using flow cytometry suggest that Os(II) complex 2 induces human breast cancer stem cell death predominantly by necroptosis, a programmed form of necrosis. The results of this study demonstrate the promise of Os(II) complex 2 in treating human breast tumors. They also represent the foundation for further preclinical and clinical studies and applications of Os(II) complex 2 to comply with the emergent need for human breast CSCs-specific chemotherapeutics capable to treat chemotherapy-resistant and relapsed human breast tumors.

• MeSH
• Apoptosis drug effects   MeSH
• Chloroacetates pharmacology   MeSH
• Cymenes pharmacology   MeSH
• Phenanthrolines pharmacology   MeSH
• Coordination Complexes pharmacology   MeSH
• Humans MeSH
• Neoplasm Recurrence, Local pathology   MeSH
• Cell Line, Tumor MeSH
• Neoplastic Stem Cells drug effects   metabolism   MeSH
• Tumor Microenvironment drug effects   MeSH
• Breast Neoplasms drug therapy   pathology   MeSH
• Necroptosis drug effects   MeSH
• Necrosis metabolism   MeSH
• Organoplatinum Compounds pharmacology   MeSH
• Osmium pharmacology   MeSH
• Cell Proliferation drug effects   MeSH
• Antineoplastic Agents pharmacology   MeSH
• Check Tag
• Humans MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• 4-cymene MeSH Browser
• bathophenanthroline MeSH Browser
• Chloroacetates MeSH
• Cymenes MeSH
• diammine(dichloroacetato)platinum(II) MeSH Browser
• Phenanthrolines MeSH
• Coordination Complexes MeSH
• Organoplatinum Compounds MeSH
• Osmium MeSH
• Antineoplastic Agents MeSH