Tags

Type your tag names separated by a space and hit enter

Isobavachalcone exerts anti‑proliferative and pro‑apoptotic effects on human liver cancer cells by targeting the ERKs/RSK2 signaling pathway.
Oncol Rep 2019; 41(6):3355-3366OR

Abstract

Aberrant activation of the extracellular signal‑regulated kinases (ERKs)/ribosomal S6 kinase 2 (RSK2) signaling pathway is frequently determined in various human tumor types, including liver cancer, and has been considered as a promising target for cancer chemoprevention and therapy. In the present study, using computer‑aided virtual screening and molecular docking, isobavachalcone (IBC), a natural chalcone compound, was identified to be an ATP‑competitive inhibitor targeting ERK1/2 and RSK2. Cell Counting Kit‑8, EdU incorporation and colony formation assays were used to detect the effects of IBC on cell viability and proliferation, and the results demonstrated that IBC effectively inhibited the proliferation of liver cancer HepG2 and Hep3B cells, whereas it had no notable cytotoxic effect on immortal liver L02 cells. Flow cytometric analysis and western blotting further revealed that IBC caused significant levels of apoptosis on liver cancer cells via the caspase‑dependent mitochondria pathway. The computer prediction was confirmed with pull‑down and in vitro kinase assays, in which IBC directly bound with ERK1/2 and RSK2, and dose‑dependently blocked RSK2 kinase activity in liver cancer cells. Treatment of HepG2 or Hep3B cells with IBC significantly attenuated epidermal growth factor‑induced phosphorylation of RSK2 and resulted in the reduced activation of its downstream substrates including cAMP response element‑binding protein, activating transcription factor 1, histone H3 and activating protein‑1. Enforced RSK2 expression in L02 cells could increase the effect of IBC on suppressing cell growth. Conversely, knockdown of RSK2 reduced the inhibitory effect of IBC on HepG2 cell proliferation. Overall, the present data indicated that ERKs/RSK2 signaling serves a pivotal role in IBC‑induced suppression of liver cancer cells and that IBC may be a potential therapeutic candidate for human cancer with elevated ERKs/RSK2 activity.

Authors+Show Affiliations

Department of Pathophysiology, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.China‑American Cancer Research Institute, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.Medical College of Xiamen University, Xiamen, Fujian 361000, P.R. China.Faculty of Laboratory Medicine, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.China‑American Cancer Research Institute, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.China‑American Cancer Research Institute, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.China‑American Cancer Research Institute, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.China‑American Cancer Research Institute, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.Department of Pathophysiology, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30942462

Citation

Li, Binbin, et al. "Isobavachalcone Exerts Anti‑proliferative and Pro‑apoptotic Effects On Human Liver Cancer Cells By Targeting the ERKs/RSK2 Signaling Pathway." Oncology Reports, vol. 41, no. 6, 2019, pp. 3355-3366.
Li B, Xu N, Wan Z, et al. Isobavachalcone exerts anti‑proliferative and pro‑apoptotic effects on human liver cancer cells by targeting the ERKs/RSK2 signaling pathway. Oncol Rep. 2019;41(6):3355-3366.
Li, B., Xu, N., Wan, Z., Ma, L., Li, H., Cai, W., ... He, Z. (2019). Isobavachalcone exerts anti‑proliferative and pro‑apoptotic effects on human liver cancer cells by targeting the ERKs/RSK2 signaling pathway. Oncology Reports, 41(6), pp. 3355-3366. doi:10.3892/or.2019.7090.
Li B, et al. Isobavachalcone Exerts Anti‑proliferative and Pro‑apoptotic Effects On Human Liver Cancer Cells By Targeting the ERKs/RSK2 Signaling Pathway. Oncol Rep. 2019;41(6):3355-3366. PubMed PMID: 30942462.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isobavachalcone exerts anti‑proliferative and pro‑apoptotic effects on human liver cancer cells by targeting the ERKs/RSK2 signaling pathway. AU - Li,Binbin, AU - Xu,Nansong, AU - Wan,Zheng, AU - Ma,Li, AU - Li,Huahui, AU - Cai,Weijie, AU - Chen,Xiumei, AU - Huang,Zunnan, AU - He,Zhiwei, Y1 - 2019/04/02/ PY - 2018/09/20/received PY - 2019/03/19/accepted PY - 2019/4/4/pubmed PY - 2019/8/16/medline PY - 2019/4/4/entrez SP - 3355 EP - 3366 JF - Oncology reports JO - Oncol. Rep. VL - 41 IS - 6 N2 - Aberrant activation of the extracellular signal‑regulated kinases (ERKs)/ribosomal S6 kinase 2 (RSK2) signaling pathway is frequently determined in various human tumor types, including liver cancer, and has been considered as a promising target for cancer chemoprevention and therapy. In the present study, using computer‑aided virtual screening and molecular docking, isobavachalcone (IBC), a natural chalcone compound, was identified to be an ATP‑competitive inhibitor targeting ERK1/2 and RSK2. Cell Counting Kit‑8, EdU incorporation and colony formation assays were used to detect the effects of IBC on cell viability and proliferation, and the results demonstrated that IBC effectively inhibited the proliferation of liver cancer HepG2 and Hep3B cells, whereas it had no notable cytotoxic effect on immortal liver L02 cells. Flow cytometric analysis and western blotting further revealed that IBC caused significant levels of apoptosis on liver cancer cells via the caspase‑dependent mitochondria pathway. The computer prediction was confirmed with pull‑down and in vitro kinase assays, in which IBC directly bound with ERK1/2 and RSK2, and dose‑dependently blocked RSK2 kinase activity in liver cancer cells. Treatment of HepG2 or Hep3B cells with IBC significantly attenuated epidermal growth factor‑induced phosphorylation of RSK2 and resulted in the reduced activation of its downstream substrates including cAMP response element‑binding protein, activating transcription factor 1, histone H3 and activating protein‑1. Enforced RSK2 expression in L02 cells could increase the effect of IBC on suppressing cell growth. Conversely, knockdown of RSK2 reduced the inhibitory effect of IBC on HepG2 cell proliferation. Overall, the present data indicated that ERKs/RSK2 signaling serves a pivotal role in IBC‑induced suppression of liver cancer cells and that IBC may be a potential therapeutic candidate for human cancer with elevated ERKs/RSK2 activity. SN - 1791-2431 UR - https://www.unboundmedicine.com/medline/citation/30942462/Isobavachalcone_exerts_anti‑proliferative_and_pro‑apoptotic_effects_on_human_liver_cancer_cells_by_targeting_the_ERKs/RSK2_signaling_pathway_ L2 - http://www.spandidos-publications.com/or/41/6/3355 DB - PRIME DP - Unbound Medicine ER -