novobiocin/neoplasms

Previous reports from this laboratory have demonstrated that novobiocin produces supraadditive cytotoxicity and increases the formation of drug-stabilized topoisomerase II-DNA covalent complexes in WEHI-3B myelomonocytic leukemia and A549 lung carcinoma cells when combined with etoposide (VP-16).

We conducted the first phase 2 and pharmacologic study to evaluate the combination of novobiocin (a coumeromycin antibiotic that has been shown to augment alkylating agent cytotoxicity in experimental models) and high-dose cyclophosphamide and thiotepa followed by autologous marrow support in women

Novobiocin, a commercially available oral antibiotic, inhibits DNA topoisomerase II in a manner shown in cell culture to enhance the cytotoxicity of alkylating agents and cisplatin. Thirty-six patients were entered on a Phase II trial using high-dose cisplatin (100 mg/m2 on days 1 and 8 for four

OBJECTIVE Resistance to alkylators may potentially be overcome by drugs that inhibits DNA repair, thus improving the efficacy of high-dose chemotherapy. This trial was performed to determine if novobiocin, an agent that inhibits DNA repair, could be given with high-dose alkylators. Study aims were

Our previous in vitro studies demonstrated marked synergy with alkylating agents when novobiocin was present during and after alkylating agent exposure. To determine whether this effect is observed in vivo, novobiocin was administered daily for 3 days prior to alkylating agent treatment, during

In this study, we investigated the anticancer efficacy of pegylated liposomes containing 6BrCaQ, an hsp90 inhibitor derived from novobiocin. 6BrCaQ has been previously identified as the most potent compound in a series of quinoleic novobiocin analogs but is poorly water-soluble. We investigated, for

Novobiocin is a natural product that binds the Hsp90 C-terminus and manifests Hsp90 inhibitory activity. Structural investigations on novobiocin led to the development of both anti-cancer and neuroprotective agents. The varied pharmacological activity manifested by these novobiocin analogs prompted

Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ∼700-fold improved anti-proliferative activity versus the natural product as

Selective hsp90 inhibitors simultaneously destabilize and deplete key signaling proteins involved in cell proliferation and survival, angiogenesis, and metastasis. Investigation of novobiocin analogues lacking the noviose moiety as novel inhibitors of hsp90 was carried out. A novel series of

Breast cancer resistance protein (BCRP/ABCG2) of an ATP-binding cassette half-transporter confers resistance against mitoxantrone and camptothecin derivatives of topotecan and irinotecan. Novobiocin, a coumermycin antibiotic, is known to enhance anticancer drug sensitivity of cancer cells in vitro

6BrCaQ is a promising anti-cancer agent derived from novobiocin, which has been shown to inhibit Hsp90. 6BrCaQ was loaded into nanometer-scaled phospholipid vesicles (liposomes) suitable for drug delivery to solid tumors. The effective incorporation of the drug within the phospholipid bilayer was

Heat shock protein 90 (Hsp90) is a molecular chaperone that is responsible for the folding and maturation of client proteins that are associated with all ten hallmarks of cancer. Hsp90 N-terminal pan inhibitors have experienced unfavorable results in clinical trials due to induction of the heat

The 90 kDa heat shock proteins (Hsp90), which are integrally involved in cell signaling, proliferation, and survival, are ubiquitously expressed in cells. Many proteins in tumor cells are dependent upon the Hsp90 protein folding machinery for their stability, refolding, and maturation. Inhibition of

BACKGROUND Novobiocin was shown to sensitize cancer cells to etoposide and alkylating agents. Human breast carcinoma cells exposed to topotecan (MCF7/TPT300 cells) developed resistance to both mitoxantrone and topotecan. An ATP-binding cassette family protein BCRP/MXR/ABCP was overexpressed in

Centrifugal elutriation was used to obtain synchronized cell populations in various cell cycle phases without prior growth-perturbing manipulation. Treatment of these subpopulations with novobiocin (NOVO), a putative inhibitor of the mammalian topoisomerase II enzyme, revealed a unique cell cycle