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Moringa isothiocyanate complexed with α-cyclodextrin: a new perspective in neuroblastoma treatment
Sabrina Giacoppo1, Renato Iori2, Patrick Rollin3
1IRCCS Centro Neurolesi "Bonino-Pulejo", Via Provinciale Palermo, Contrada Casazza, 98124, Messina, Italy.
Background:
Several lines of evidence suggest the consume of natural products for cancer prevention or treatment. In particular, isothiocyanates (ITCs) exerting anti-cancer properties, have received great interest as potential chemotherapeutic agents. This study was designed to assess the anti-proliferative activities of a new preparation of Moringa oleifera-derived 4-(α-L-rhamnopyranosyloxy)benzyl ITC (moringin) complexed with alpha-cyclodextrin (moringin + α-CD; MAC) on SH-SY5Y human neuroblastoma cells. This new formulation arises in the attempt to overcome the poor solubility and stability of moringin alone in aqueous media.
Methods:
SH-SY5Y cells were cultured and exposed to increasing concentrations of MAC (1.0, 2.5 and 5.0 μg). Cell proliferation was examined by MTT and cell count assays. The cytotoxic activity of the MAC complex was assessed by lactate dehydrogenase (LDH) assay and trypan blue exclusion test. In addition, western blotting analyses for the main apoptosis-related proteins were performed.
Results:
Treatment of SH-SY5Y cells with the MAC complex reduced cell growth in concentration dependent manner. Specifically, MAC exhibited a potent action in inhibiting the PI3K/Akt/mTOR pathway, whose aberrant activation was found in many types of cancer. MAC was also found to induce the nuclear factor-κB (NF-κB) p65 activation by phosphorylation and its translocation into the nucleus. Moreover, treatment with MAC was able to down-regulate MAPK pathway (results focused on JNK and p38 expression). Finally, MAC was found to trigger apoptotic death pathway (based on expression levels of cleaved-caspase 3, Bax/Bcl-2 balance, p53 and p21).
Conclusion:
These findings suggest that use of MAC complex may open novel perspectives to improve the poor prognosis of patients with neuroblastoma.
Insights
This study shows that a new Moringa oleifera-derived complex (MAC) effectively inhibits neuroblastoma cell growth. MAC triggers apoptosis and modulates key cancer pathways, offering potential for improved neuroblastoma treatment.
Area of Science:
- Natural Product Chemistry
- Cancer Biology
- Neuro-oncology
Background:
- Isothiocyanates (ITCs) show anti-cancer properties, with potential as chemotherapeutic agents.
- Moringin, a Moringa oleifera-derived ITC, has limited solubility and stability.
- A new alpha-cyclodextrin complex (MAC) was developed to enhance moringin's properties.
Purpose of the Study:
- To evaluate the anti-proliferative effects of the moringin + alpha-cyclodextrin (MAC) complex.
- To assess MAC's impact on SH-SY5Y human neuroblastoma cells.
- To investigate the molecular mechanisms underlying MAC's anti-cancer activity.
Main Methods:
- SH-SY5Y cells were treated with varying concentrations of the MAC complex.
- Cell proliferation was measured using MTT and cell count assays.
- Cytotoxicity was assessed via LDH assay and trypan blue exclusion; apoptosis-related proteins were analyzed by Western blotting.
Main Results:
- The MAC complex demonstrated significant, dose-dependent inhibition of SH-SY5Y cell proliferation.
- MAC modulated key cancer pathways, including inhibition of PI3K/Akt/mTOR and MAPK pathways, and activation of NF-κB.
- Treatment with MAC induced apoptosis in neuroblastoma cells, evidenced by altered expression of apoptosis markers.
Conclusions:
- The MAC complex exhibits potent anti-proliferative and pro-apoptotic effects on neuroblastoma cells.
- MAC's ability to target critical cancer signaling pathways suggests therapeutic potential.
- This novel formulation may offer new therapeutic avenues for improving neuroblastoma patient prognosis.
