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Pinocembrin-Enriched Fractions of Elytranthe parasitica (L.) Danser Modulates Apoptotic and MAPK Cellular Signaling in HepG2 cells Pinocembrin-Enriched Fractions of Elytranthe parasitica (L.) Danser Modulates Apoptotic and MAPK Cellular Signaling in HepG2 cells.
Anti-cancer Agents in Medicinal Chemistry 2018 September 11
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 expression of apoptosis and mitogen-activated 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 was 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) was 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.
OBJECTIVE: In the study, we investigated the effect of EP fractions on expression of apoptosis and mitogen-activated 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 was 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) was 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.
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