The flavonoids are of great interest due to their antioxidant and anti-cancerous potential. The present study investigated the Morin extracted from mulberry leaves and its anti-cancerous mechanism via cell inhibition, cell cycle analysis, apoptosis, mRNA expression and antioxidant mechanism through reactive oxygen species generation. Morin inhibited the proliferation of HeLa cells at IC50 of 214.28 μM and led to morphological changes, followed by induction of cell cycle arrest in G2/M-phase and ultimately resulted into apoptosis. Morin-induced G2/M-phase arrest was accompanied by the increase in mRNA expression of p53, p21 and Wee 1 genes and decreased levels of CDK1, Cdc25c, Survivin, cyclin B1and CHK2. Morin-induced apoptosis was regulated through multiple pathways, including intrinsic and extrinsic pathway. The underlying mechanisms consisted of increased mRNA expression of Bax, Bad, cytochrome c, Apaf-1, caspases-9, DR3, DR5, FasL, FADD, caspases-10, PARP, PI3K, AKT, mTOR, P70S6K and Smac genes as well as decreased expression of Bcl-2, Bcl-xL, AMPK, cIAP-1, cIAP-2, PKCε and NF-kβ. In addition, Morin treatment resulted in the generation of intracellular ROS, which play an essential role in the induction of apoptosis. The present study recommends the use of Morin in the development of functional foods with anti-cancerous potential in the future.
Keywords: Apoptosis; Cell cycle; Cervical cancer; Molecular mechanism; Morin; Mulberry.
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