Dendrosomal Curcumin Nanoformulation Modulate Apoptosis-Related Genes And Protein Expression In Hepatocarcinoma Cell Lines: Possible Anti Proliferative Effects

Nosratollah ZARGHAMI, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Iran
MONTAZERI M. 1, 2 , PILEHVAR-SOLTANAHMADI Y. 1, 2 , ZARGHAMI F. 3

1 Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
3 Imam Reza Teaching Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

Purpose: The side-effects observed in conventional therapies have made them unpromising in curing Hepatocellular carcinoma; therefore, developing novel treatments can be an overwhelming significance. One of such novel agents is curcumin which can induce apoptosis in various cancerous cells, however, its poor solubility is restricted its application. To overcome this issue, this paper employed dendrosomal nanocurcumin was employed to in prevent hepatocarcinoma in both RNA and protein levels.
Methods: Hepatocarcinoma cells, p53 wild-type HepG2 and p53 mutant Huh7, were treated with dendrosomal nanocurcumin and investigated for toxicity study using MTT assay. Cell cycle distribution and apoptosis were analyzed using Flow-cytometry and Annexin-V-FLUOS/PI staining.  Real-time PCR and Western blot were employed to analyze p53, BAX, Bcl-2, p21 and Noxa in dendrosomal nanocurcumin-treated cells.
Results: dendrosomal nanocurcumin inhibited the growth in the form of time-dependent manner, while the carrier alone was not toxic to the cell. Flow-cytometry data showed the constant concentration of 20µM dendrosomal nanocurcumin during the time significantly increases cell population in SubG1 phase. Annexin-V-PI test showed curcumin-induced apoptosis was enhanced in Huh7 as well as HepG2, compared to untreated cells. Followed by treatment, mRNA expression of p21, BAX, and Noxa increased, while the expression of Bcl-2 decreased, and unlike HepG2, Huh7 showed down-regulation of p53.
Conclusions: In summary, dendrosomal nanocurcumin-treated hepatocellular carcinoma cells undergo apoptosis by changing the expression of genes involved in the apoptosis and proliferation processes. These findings suggest that dendrosomal nanocurcumin, as a plant-originated therapeutic agent, could be applied in cancer treatment.