title: Cancer cell sensitization and improved treatment efficacy by combined sodium butyrate and paclitaxel formulations is cancer-type specific.
abstract: We queried whether cancer treatment by combinations of paclitaxel and butyrate - free or formulated in drug delivery systems - can improve therapeutic responses compared to each drug alone. Combination treatments were conducted with HT-29 and HeLa cells, as representatives of differentiation-induced and cell-death-induced cancer lines, respectively. Pre-treatment of the HT-29 cells with butyrate (at doses inducing differentiation), followed by butyrate+paclitaxel generated changes in cell cycle profile, increased the level of dead cells beyond that of each drug alone, and allowed reduction in paclitaxel doses. A similar combination treatment of HeLa cells was detrimental, indicating that whether the combination is beneficial or not is cancer-type specific. We hypothesize that while butyrate-treated HT-29 cells became sensitive to paclitaxel-induced Fas-mediated apoptosis, butyrate-adapted HeLa cells became apoptosis-resistant. We next tested the same drug combination on HT-29 cells, but each drug in a specific tumor-targeted carrier. The combination of drug carriers outperformed an equidose combination of the free drugs, showing potential to achieve high therapeutic responses (even in drug-resistant cells) at significantly lower and detergent-free paclitaxel doses, which should allow for reduction in adverse effects and risks of toxicity.
authors.affiliation: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Ilia
authors.initials: I
authors.lastname: Rivkin
authors.affiliation: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Keren
authors.initials: K
authors.lastname: Cohen
authors.affiliation: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Bod
authors.affiliation: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Mirit
authors.initials: M
authors.lastname: Argov
authors.affiliation: Department of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv 69978, Israel. Electronic address: rimona@tauex.tau.ac.il.
authors.forename: Rimona
authors.initials: R
authors.lastname: Margalit
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D020148:Butyric Acid / Q000008:administration & dosage / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage / Q000494:pharmacology*; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D020148:Butyric Acid; D017239:Paclitaxel
keywords: Apoptosis; Butyrate; Cancer cells; Differentiation; Drug delivery; Paclitaxel