Crude extract of Rheum palmatum L. Induces cell cycle arrest S phase and apoptosis through mitochondrial-dependent pathways in U-2 OS human osteosarcoma cells

Environ Toxicol. 2016 Aug;31(8):957-69. doi: 10.1002/tox.22105. Epub 2015 Feb 17.


Cancer is the second cause of death in children. Osteosarcoma is the most common primary malignancy of solid bone cancer primarily affecting adolescents and young adults. In the Chinese population, the crude extract of Rheum palmatum L. (CERP) has been used for treating different diseases, including SARS, rheumatoid arthritis, coxsackievirus B3, and human colon cancer cell, pancreatic cancer. There are no reports on CERP and human osteosarcoma cells. The present study examined effects of CERP on cytotoxicity including cell cycle distribution and cell death (apoptosis) in U-2 OS human osteosarcoma cells. CERP significantly induced S phase arrest in U-2 OS cells in a dose-dependent. CERP produced DNA damage and DNA condensation. Other effects of CERP were stimulation of ROS and Ca(2+) , mitochondria impairment, and activation of caspase-3, -8, and -9. CERP increased the levels of Bax, Bak, Bad, cyclin B, Fas, PARP, GRP78, GADD153, AIF, Endo G, Calpain-2, p21, and p27, but decreased the levels of Bcl-2, BCL-X, XIAP, Akt, CDC25A, CDK2, Cyclin A, and Cyclin E of U-2 OS cells. It was also observed that CERP promoted the expression of AIF, Endo G, GADD153, and cytochrome c. These results indicate that CERP has anticancer effects in vitro and provide the foundation for in vivo studies of animal models of osteosarcoma. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 957-969, 2016.

Keywords: apoptosis; cell cycle arrest; crude extract of Rheum palmatum L. (CERP); human osteosarcoma cells U-2 OS.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis Regulatory Proteins / metabolism
  • Bone Neoplasms / drug therapy
  • Bone Neoplasms / pathology
  • Calcium Signaling
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • DNA Damage
  • Drug Screening Assays, Antitumor
  • Drugs, Chinese Herbal / pharmacology*
  • Endoplasmic Reticulum Chaperone BiP
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Osteosarcoma / drug therapy
  • Osteosarcoma / pathology
  • Protein Transport
  • Reactive Oxygen Species / metabolism
  • Rheum / chemistry
  • S Phase Cell Cycle Checkpoints / drug effects*


  • Antineoplastic Agents, Phytogenic
  • Apoptosis Regulatory Proteins
  • Drugs, Chinese Herbal
  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • Reactive Oxygen Species