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Antibiotic anisomycin induces cell cycle arrest and apoptosis through inhibiting mitochondrial biogenesis in

Chuanhua Cao1, Haiying Yu1, Feng Wu2

  • 1Department of Oncology, The Affiliated Hospital of Hubei University of Arts and Science, Xiangyang Central Hospital, 136 Jingzhou Road, Xiangyang, Hubei, 441021, People's Republic of China.

Journal of Bioenergetics and Biomembranes
|November 23, 2017
PubMed

Insights

Anisomycin, an antibiotic, shows anti-cancer effects against osteosarcoma by inhibiting cell proliferation and inducing apoptosis. It targets mitochondrial biogenesis, enhancing chemotherapy efficacy with less impact on normal cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Anisomycin exhibits anti-cancer properties in various cancers, but its mechanisms remain unclear.
  • Osteosarcoma treatment often requires novel therapeutic strategies to improve outcomes.

Purpose of the Study:

  • To investigate the efficacy of anisomycin in osteosarcoma.
  • To elucidate the anti-cancer mechanisms of anisomycin in osteosarcoma cells.
  • To evaluate anisomycin's potential to sensitize osteosarcoma to chemotherapy.

Main Methods:

  • Cell cycle analysis (G2/M arrest) and apoptosis assays (caspase-dependent).
  • Western blotting for cell cycle regulatory proteins (cyclin B, Rb, E2F-1).
  • In vitro and in vivo xenograft mouse models assessing anisomycin and doxorubicin efficacy.
  • Mitochondrial function assays (membrane potential, Complex I activity, ATP production) and rescue experiments with acetyl-L-Carnitine (ALCAR).

Main Results:

  • Anisomycin inhibited osteosarcoma cell proliferation by inducing G2/M phase arrest and apoptosis.
  • It demonstrated selective toxicity towards osteosarcoma cells compared to normal NIH3T3 cells.
  • Anisomycin enhanced doxorubicin's anti-osteosarcoma effects both in vitro and in vivo.
  • The drug suppressed mitochondrial biogenesis by reducing membrane potential, Complex I activity, and ATP production.
  • Acetyl-L-Carnitine (ALCAR) partially reversed anisomycin's inhibitory effects.

Conclusions:

  • Anisomycin is an effective anti-osteosarcoma agent.
  • Its mechanism involves the inhibition of mitochondrial biogenesis.
  • Anisomycin holds potential as a therapeutic agent for osteosarcoma, particularly in combination with chemotherapy.
Keywords:
AnisomycinMitochondria biogenesisOsteosarcoma

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