PMID- 20429876 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20110714 LR - 20211020 IS - 1757-2215 (Electronic) IS - 1757-2215 (Linking) VI - 3 DP - 2010 Apr 29 TI - Curcumin induces chemo/radio-sensitization in ovarian cancer cells and curcumin nanoparticles inhibit ovarian cancer cell growth. PG - 11 LID - 10.1186/1757-2215-3-11 [doi] AB - BACKGROUND: Chemo/radio-resistance is a major obstacle in treating advanced ovarian cancer. The efficacy of current treatments may be improved by increasing the sensitivity of cancer cells to chemo/radiation therapies. Curcumin is a naturally occurring compound with anti-cancer activity in multiple cancers; however, its chemo/radio-sensitizing potential is not well studied in ovarian cancer. Herein, we demonstrate the effectiveness of a curcumin pre-treatment strategy for chemo/radio-sensitizing cisplatin resistant ovarian cancer cells. To improve the efficacy and specificity of curcumin induced chemo/radio sensitization, we developed a curcumin nanoparticle formulation conjugated with a monoclonal antibody specific for cancer cells. METHODS: Cisplatin resistant A2780CP ovarian cancer cells were pre-treated with curcumin followed by exposure to cisplatin or radiation and the effect on cell growth was determined by MTS and colony formation assays. The effect of curcumin pre-treatment on the expression of apoptosis related proteins and beta-catenin was determined by Western blotting or Flow Cytometry. A luciferase reporter assay was used to determine the effect of curcumin on beta-catenin transcription activity. The poly(lactic acid-co-glycolic acid) (PLGA) nanoparticle formulation of curcumin (Nano-CUR) was developed by a modified nano-precipitation method and physico-chemical characterization was performed by transmission electron microscopy and dynamic light scattering methods. RESULTS: Curcumin pre-treatment considerably reduced the dose of cisplatin and radiation required to inhibit the growth of cisplatin resistant ovarian cancer cells. During the 6 hr pre-treatment, curcumin down regulated the expression of Bcl-XL and Mcl-1 pro-survival proteins. Curcumin pre-treatment followed by exposure to low doses of cisplatin increased apoptosis as indicated by annexin V staining and cleavage of caspase 9 and PARP. Additionally, curcumin pre-treatment lowered beta-catenin expression and transcriptional activity. Nano-CUR was successfully generated and physico-chemical characterization of Nano-CUR indicated an average particle size of ~70 nm, steady and prolonged release of curcumin, antibody conjugation capability and effective inhibition of ovarian cancer cell growth. CONCLUSION: Curcumin pre-treatment enhances chemo/radio-sensitization in A2780CP ovarian cancer cells through multiple molecular mechanisms. Therefore, curcumin pre-treatment may effectively improve ovarian cancer therapeutics. A targeted PLGA nanoparticle formulation of curcumin is feasible and may improve the in vivo therapeutic efficacy of curcumin. FAU - Yallapu, Murali M AU - Yallapu MM AD - Cancer Biology Research Center, Sanford Research/University of South Dakota, Sioux Falls, SD 57105, USA. Chauhans@sanfordhealth.org. FAU - Maher, Diane M AU - Maher DM FAU - Sundram, Vasudha AU - Sundram V FAU - Bell, Maria C AU - Bell MC FAU - Jaggi, Meena AU - Jaggi M FAU - Chauhan, Subhash C AU - Chauhan SC LA - eng PT - Journal Article DEP - 20100429 PL - England TA - J Ovarian Res JT - Journal of ovarian research JID - 101474849 PMC - PMC2880315 EDAT- 2010/05/01 06:00 MHDA- 2010/05/01 06:01 PMCR- 2010/04/29 CRDT- 2010/05/01 06:00 PHST- 2010/02/11 00:00 [received] PHST- 2010/04/29 00:00 [accepted] PHST- 2010/05/01 06:00 [entrez] PHST- 2010/05/01 06:00 [pubmed] PHST- 2010/05/01 06:01 [medline] PHST- 2010/04/29 00:00 [pmc-release] AID - 1757-2215-3-11 [pii] AID - 10.1186/1757-2215-3-11 [doi] PST - epublish SO - J Ovarian Res. 2010 Apr 29;3:11. doi: 10.1186/1757-2215-3-11.