Effects of phytochemicals on neuroblastoma and metastatic potential

Objective: To explore antitumoral effects of allicin, resveratrol, their changing effects on cisplatin; and effect of these phytochemicals on the expression of metastasis related genes in neuroblastoma cell lines. Method: Kelly and SH-SY5Y human neuroblastoma cell lines were used. Groups: Group1:Control, Group2:Cisplatin, Group3:Allicin, Group4:Resveratrol, Group5:Cisplatin+Allicin, Group6:Cisplatin+Resveratrol. Cytotoxic effects of agents were assessed MTT and LDH assays, apoptosis was determined by TUNEL. DDX1 and 84 custom array genes of tumor metastasis were determined by RT-PCR. Expressions were calculated at manufacturer?s online PCR expression analysis page. Mann-Whitney-U, chi-square, correlation analysis were used. Results: Allicin didn?t cause cytotoxicity, apoptosis, also didn?t change cytotoxic, apoptotic effects of cisplatin. Resveratrol didn?t cause apoptosis, however cause cytotoxicity. Cytotoxic effect of cisplatin didn?t change, but apoptotic effect of cisplatin diminished by resveratrol. KELLY: Groups3/4/5/6: CCL7, CDH1, CTSL1, ETV4, FXYD5, KISS1R, HTATIP2, IL1B, IL8RB, ITGA7, KISS1, MMP10, MMP13, MMP3, MMP7, MYC, MYCL1, SYK, TIMP4, TRPM1, TNFSF10 expressions increased. Groups2/3/4/5/6: RB1, DENR expressions decreased. Group4: DDX1, nm23-H1 increased, nm23-H2 decreased. Group5 nm23-H1 increased. SHSY5Y: Groups3/5: KISS1, TNFSF10, MMP10, TRPM1, IGF1, MMP13, MMP7, additionally MMP3, CCL7, TIMP4, ITGA7 expressions decreased in group3. Groups4/6: MET, KISS1, IGF1, TNSF10, MMP10, CXCL12, MMP13, MMP7, MMP3, CDH6, CCL7, TRPM1, CTSL1, FXYD5, HPSE, HTATIP2, IL1B, IL8RB, KISS1R, TIMP4 expressions decreased. Groups2/3/4/5/6: PNN, Group4: DENR expressions increased. Groups3/4/5/6: DDX1 increased, nm23-H1 decreased; in group2 DDX1, nm23-H2 increased.Conclusion: Our findings indicate allicin, resveratrol have versatile impacts on metastatic genes. Administration of these phytochemicals with or without chemoteharpy are not appropriate and should be questioned in neuroblastoma. Key Words: Neuroblastoma, Metastasis, Cisplatin, Allicin, Resveratrol