Background and strategies: Curcumin has extraordinary anticancer properties but has limited
Background and strategies: Curcumin has extraordinary anticancer properties but has limited use due to its insolubility in water and instability which leads to low systemic bioavailability. colorectal malignancy cells in vitro resulting in about 6-fold higher inhibition compared with cells treated with a solution containing BILN 2061 an equal concentration of free curcumin. Intravenous administration of curcumin-loaded CSO-SA micelles marginally suppressed tumor growth but did not increase cytotoxicity to mice as confirmed by no switch in body weight. Most importantly curcumin-loaded CSO-SA micelles were effective for inhibiting subpopulations of CD44+/CD24+ cells (putative colorectal malignancy stem cell markers) both in vitro and in vivo. Summary: The present study identifies an effective and safe means of using curcumin-loaded CSO-SA micelles for malignancy therapy. plant. It BILN 2061 has been used for many clinical purposes including as an antioxidant antibacterial anti-inflammatory agent and anticancer compound and exerts its effect primarily by influencing multiple signaling pathways.1-3 Inhibitory effects of curcumin lines have been demonstrated in various human being cancer cell lines.4 5 In addition a Phase I clinical trial showed that curcumin had low or no intrinsic toxicity in humans.6 Despite BILN 2061 these extraordinary properties curcumin continues to have limited application in the treatment of cancer because of its considerable hydrophobicity instability and poor pharmacokinetics which greatly hamper its effectiveness in vivo.7-9 Nanoscale drug delivery systems are an innovative approach to overcoming these problems. Previous efforts at encapsulating curcumin in liposomes phospholipid complexes and additional nanoparticle-based technologies have been reported which appear to provide better water dispersibility and a longer circulation time.10-14 A key attribute of an optimal drug delivery system for cancer is the ability to treat tumors effectively with minimal side effects. In addition to having good solubility in water and stability increased drug Fgfr2 permeability and improved antitumor activity in vivo are also important factors. Recently we have developed a novel stearic acid-g-chitosan oligosaccharide (CSO-SA) micelle which acts as a polymeric drug carrier due to its biocompatibility and biodegradability.15 CSO-SA micelles with their core-shell structure formed by self-aggregation from amphiphilic block or graft copolymers have many advantages for delivering anticancer agents to tumor tissue. CSO-SA micelles are stable at room temperature or at 4°C with minimal change in particle size.16 Moreover these micelles accumulate well in tumor tissue via extravasation of the nanoparticulates in fenestrated tumor vasculature.17 18 After drug loading these formulations show excellent tumor cell uptake characteristics. Importantly the drug-loaded micelles have enhanced antitumor activity and overcome multidrug resistance in tumor tissue.19 20 Accumulating evidence continues to support the fact that many types of cancers including colorectal cancer are initiated and maintained by a minority cell population known as cancer stem cells. This cell subpopulation is in charge of tumor growth and initiation BILN 2061 by continuous self-renewal and differentiation.21 22 Further recent research show that chemotherapy only destroys probably the most bulky cancer cells but does not have the capability to get rid of tumor stem cells. The success of tumor stem cells BILN 2061 leads to tumor and chemoresistance recurrence. 23 24 Therefore eradicating cancer stem cells might stand for a highly effective chemotherapeutic technique and thereby overcome tumor resistance. To be able to improve the result of tumor treatment we designed and ready curcumin-loaded CSO-SA micelles predicated on a polymeric nanosystem and examined their antitumor activity in major colorectal tumor cells. We hypothesized that CSO-SA micelles would improve the antitumor activity of curcumin by advertising its uptake in tumor cells. Our findings supply the 1st proof that curcumin-loaded CSO-SA micelles can boost antitumor effectiveness and inhibit tumor stem cells both in vitro and in vivo and claim that they could be used like a book restorative agent for tumor therapy in the foreseeable future. Components and strategies Curcumin was bought from Sigma-Aldrich St Louis MO. 3-(4 5 5 bromide (MTS) was obtained from Promega Fitchburg WI. Anti-human CD44-APC and CD24-FITC were purchased from BD Biosciences San Diego CA. Dulbecco’s Modified Eagle’s BILN 2061 Medium and Ham’s F-12 medium (DMEM-F12 medium) RPMI 1640.