Antitumor effects of curcumin in pediatric rhabdomyosarcoma in combination with chemotherapy and phototherapy in vitro.

Rhabdomyosarcoma (RMS), the most common pediatric soft tissue sarcoma, has an unfavorable outcome in advanced tumor stages with less than 30% failure­free survival. Curcumin (CUR) is a promising drug in complementary oncology with few side effects but proven efficacy in various adult oncological entities. The present study analyzed the effects of CUR on pediatric (RMS) cell lines in vitro. RMS cell lines (RD and RH30), and skeletal muscle cells (SKMC) were treated with different doses of CUR (1.5­30 µM) alone, with phototherapy (PDT, 488 nm) or in combination with vincristine (VCR) or dactinomycin (DAC). MTT assays were used for analysis of RMS tumor cell viability. Clonal cell growth was assessed via colony forming assays and migration of the cells was analyzed with scratch tests. Annexin V staining was used to determine apoptosis in flow cytometry. Possible RMS resistance towards CUR after long­term treatment was analyzed with MTT assays. CUR decreased cell viability in all assessed RMS cell lines in a concentration­dependent manner with IC50=14­20 µM. CUR enhanced the effects of the cytotoxic drugs VCR or DAC, and led to reduced migration and increased cell apoptosis. In combination with PDT, CUR decreased the cell viability in minute quantities with up to a 10­fold lower IC50 than without PDT. CUR effectively inhibited the malignant properties of pediatric RMS cells and should be focused on as a useful additional agent in standard chemotherapy of RMS in children.

Photodynamic Therapy Potentiates the Effects of Curcumin on Pediatric Epithelial Liver Tumor Cells.

BACKGROUND/AIM: Curcumin (CUM) is a promising agent in complementary oncology. The present study analyzed the photoactive properties of curcumin on pediatric epithelial liver tumor cell lines. MATERIALS AND METHODS: Hepatoblastoma cell lines (HuH6, HepT1) and hepatocellular carcinoma cell lines (HepG2, HC-AFW1) were treated with curcumin and exposed to blue light (phototherapy, 480 nm, 300 W). Cell viability (MTT tests), cellular oxidative stress (production of reactive oxygen species (ROS)) and cellular uptake/degradation of curcumin were analyzed. RESULTS: Significant loss of viability resulted from 24-48 h incubation with curcumin. With photodynamic therapy (PDT), even short time incubation (1 h) with curcumin resulted in significantly lower half maximal inhibitory concentration (IC50) (p<0.001, two-way ANOVA). Significant ROS production was observed with PDT and curcumin. CONCLUSION: Phototherapy strongly enhances the anticancer properties of curcumin in pediatric solid liver tumors in vitro.

BH3-mimetic drugs prevent tumour onset in an orthotopic mouse model of hepatoblastoma.

Drug resistance and metastasis remain major challenges in the treatment of high-risk hepatoblastoma (HB) and require the development of alternative therapeutic strategies. Modulation of apoptosis in HB cells enhances the sensitivity of these cells towards various drugs and has been discussed to enforce treatment. We investigated the impact of apoptosis sensitisers, BH3-mimetics, on the interaction between the host and HB to reduce tumour growth and dissemination while enhancing immunity. BH3-mimetics, such as obatoclax and ABT-737, enhanced the apoptosis-inducing effect of TRAIL and TNF-α resistant HB cells (HepT1 and HUH6). Tumour cell migration was inhibited by ABT-737 and more markedly by obatoclax. In an orthotopic model of HB, tumour uptake was reduced when the cells were pretreated with low concentrations of obatoclax. Only 1 of 7 mice developed HB in the liver, compared with an incidence of 0.8 in the control group. In summary, our study showed that apoptosis sensitisers had broader effects on HB cells than expected including migration and susceptibility to cytokines in addition to the known effects on drug sensitization. Sensitising HB to apoptosis may also allow resistant HB to be targeted by immune cells and prevent tumour cell dissemination.