Title:Pinocembrin-Enriched Fractions of Elytranthe parasitica (L.) Danser Modulates Apoptotic and MAPK Cellular Signaling in HepG2 Cells
VOLUME: 18 ISSUE: 11
Author(s):Nimmy Kumar, Akhila H. Shrungeswara, Sanchari B. Mallik, Subhankar Biswas, Jesil Mathew , Krishnadas Nandakumar, Jessy Mathew and Richard Lobo*
Affiliation:Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Karnataka 576104, Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Karnataka 576104, Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Karnataka 576104, Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Karnataka 576104, Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences, Karnataka 576104, Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Karnataka 576104, Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka 576104, Department of Pharmacognosy, Manipal College of Pharmaceutical Sciences, Karnataka 576104
Keywords:Apoptosis, cancer, Elytranthe, hepatocellular, HepG2, MAPK.
Abstract:Background: Hepatocellular carcinoma (HCC) is the fifth leading cause of cáncer mortality. Elytranthe
parasitica (L.) Danser (EP), a hemiparasitic plant (Loranthaceae) has potent anti-cancer properties.
Objective: In the study, we investigated the effect of EP fractions on the expression of apoptosis and mitogenactivated
protein kinase (MAPK) markers deregulated in HCC. Bioactivity fractionation was performed to isolate the
phytochemical(s) exerting anti-tumor activity in HepG2 cells.
Method: Anti-proliferative, clonogenic and anti-metastatic effects of EP fractions were examined in hepatocellular
carcinoma cell line, HepG2 by Sulphorhodamine B, colony formation and scratch wound assays respectively in
hepatocellular cell line, HepG2. The effects of EP fractions on key markers of apoptosis and MAPK signaling pathways
were explored.
Key findings: EP bioactive fractions showed significant anti-tumor potential, reduced clonogenicity and considerably
inhibited cell migration in HepG2 cells in vitro. The fractions augmented annexin V binding and induced apoptosis
by causing cell cycle arrest at G2/M and S phase checkpoints. The fractions increased expression levels of p53, bad,
cleaved PARP (Poly ADP ribose polymerase) and cleaved Caspase-3. Expression levels of phosphorylated ERK1/2
(Extracellular signal-regulated kinase) were downregulated. Pinocembrin-7-O-ß-D-glucoside and chrysin were isolated
and characterized for the first time from Elytranthe parasitica (L.) Danser.
Conclusion: Our findings reveal that EP fractions induced cell cycle arrest and triggered apoptosis in HepG2 cells by
upregulating apoptosis and deactivating MAPK pathway. It signifies that pinocembrin glycoside and chrysin are
bioactive phytochemicals contributing to the potent anti-hepatocarcinoma effects on HepG2 cells. Hence, bioactive
EP fractions could be used as a therapeutic agent for effective HCC therapy.
