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Oridonin induced apoptosis through Akt and MAPKs signaling pathways in human osteosarcoma cells

Song Jin1, Jing-Nan Shen, Jin Wang

  • 1Department of Orthopedic Surgery, First Affiliated Hospital, 74 Zhongshan 2 Road, Guangzhou, Guangdong 510080, China.

Cancer Biology & Therapy
|January 16, 2007
PubMed

Insights

Oridonin, a compound from Rabdosia rubescens, effectively suppresses osteosarcoma cell growth and triggers apoptosis. It acts by modulating key signaling pathways like Akt, ERK, and MAPKs, leading to programmed cell death.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • Oridonin, a diterpenoid from Rabdosia rubescens, exhibits anti-proliferative and apoptosis-inducing properties in various cell types.
  • The precise mechanisms underlying oridonin's effects, particularly in osteosarcoma, require further elucidation.

Purpose of the Study:

  • To investigate the apoptosis-inducing effects of oridonin in human osteosarcoma cells.
  • To elucidate the molecular mechanisms responsible for oridonin-mediated apoptosis and proliferation suppression.

Main Methods:

  • Treatment of human osteosarcoma cell lines (U2OS, MG63, SaOS-2) with varying concentrations and durations of oridonin.
  • Analysis of apoptosis markers, including cytochrome c release, caspase activation (caspase-9, caspase-3), and poly(ADP-ribose) polymerase (PARP) cleavage.
  • Assessment of signaling pathway modulation, focusing on Akt, FOXO, GSK3, ERK, p38 MAPK, JNK, and inhibitor of apoptosis proteins (IAPs).

Main Results:

  • Oridonin demonstrated concentration- and time-dependent inhibition of osteosarcoma cell proliferation and induction of apoptosis.
  • Oridonin triggered the mitochondrial apoptosis pathway, evidenced by cytochrome c release and subsequent caspase cascade activation, which was blocked by z-VAD-fmk.
  • Oridonin modulated signaling pathways by dephosphorylating Akt, FOXO, and GSK3, decreasing ERK phosphorylation, and increasing p38 MAPK and JNK phosphorylation, while down-regulating IAPs.

Conclusions:

  • Oridonin effectively suppresses proliferation and induces apoptosis in human osteosarcoma cells.
  • The mechanism involves inactivation of Akt and ERK, activation of p38 MAPK and JNK signaling, and activation of the mitochondria- and caspase-dependent apoptotic pathway.
  • Oridonin represents a potential therapeutic agent for osteosarcoma, warranting further investigation.

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