Background and Objectives: Hepatocellular carcinoma is considered the third most frequent cause of cancer-related death. This study was aimed to discover efficacious and cheap alternative natural medicines with less or no adverse effects of chemotherapy. The possible anticancer potential and underlying mechanisms of combined Cinnamomum zeylanicum (Cinnamon) and Cymbopogon citratus (lemongrass) aqueous extracts on human hepatocellular carcinoma cells (HepG2) was investigated. Methodology: Antioxidant potential, flavonoids and total phenolic content (TPC) of both extracts were evaluated. Cytotoxic activity of combined extracts was assessed using neutral red uptake method. Morphological changes were evaluated using Giemsa and Acridine orange/ ethidium bromide (AO/EBr) fluorescent staining characterized with the apoptotic nuclear and cytoplasmic morphological changes significantly (P≤0.05) recorded at both doses of combined treatment. Cell proliferation and cell apoptosis capability were assessed using Ki-67 and Bcl-2 immunocytochemical reaction respectively. Results: Cytoplasmic morphological changes were characterized by apoptotic and cytotoxic features (P≤0.05) at both doses of combined treatment. Anti-proliferation and cell apoptosis capaility of combined treatment on HepG2 cells proved with a decrease in mitotic index, Ki-67 expression and Bcl-2 down regulation. Additionally, DNA fragmentation on agaraose gel showed a cytotoxic effect and micronucleus evidence (P≤0.05) was increased with dose dependent manner. Autophagy was evaluated as a result of extracts treatment with a significant (P≤0.05) increase of autophagic vesicles in treated HepG2 cells was observed among the treated groups. Conclusion: Combined treatment of cinnamon and lemongrass extracts can exert anti-cancer effects as apoptosis induction, autophagic cell death activation and inhibiting cell proliferation on HepG2 cells.
Key words: Cinnamomum zeylanicum, Cymbopogon citratus, apoptosis, autophagy, anti-proliferation, HepG2 cells
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