Cardamonin inhibits the growth of human osteosarcoma cells through activating P38 and JNK signaling pathway

Biomed Pharmacother. 2021 Feb:134:111155. doi: 10.1016/j.biopha.2020.111155. Epub 2020 Dec 25.

Abstract

Osteosarcoma (OS) is the most common type of bone malignant tumors. Clinical commonly used therapeutic drugs of OS treatment are prone to toxic and side effects, so it is very urgent to develop new drugs with low toxicity and low side effects. As a Chinese herbal medicine, Cardamonin (CAR) (C16H14O4) has inhibitory effects in various tumors. In the present study, we investigated the effects of CAR on OS cells in vitro and in vivo. We found that CAR inhibited cell proliferation, reduced migration, decreased invasion, and induced G2 / M arrest of OS cells. Notably, we demonstrated that CAR had no obvious effect on proliferation and apoptosis of normal cells. Besides, CAR repressed tumor growth of OS cells in xenograft mouse model. Mechanically, we found that CAR increased the phosphorylation level of P38 and JNK. In summary, our research validates that CAR may inhibit the proliferation, migration, and invasion of OS and promote apoptosis possibly by activating P38 and JNK Mitogen-activated protein kinase (MAPK) signaling pathway.

Keywords: Cardamonin; Mitogen-activated protein kinase; Osteosarcoma; Signaling pathway.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Bone Neoplasms / drug therapy*
  • Bone Neoplasms / enzymology
  • Bone Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Chalcones / pharmacology*
  • Enzyme Activation
  • Female
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Osteosarcoma / drug therapy*
  • Osteosarcoma / enzymology
  • Osteosarcoma / pathology
  • Phosphorylation
  • Signal Transduction
  • Xenograft Model Antitumor Assays
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Antineoplastic Agents, Phytogenic
  • Chalcones
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • cardamonin