Carnosine Inhibits the Proliferation of Human Cervical Gland Carcinoma Cells Through Inhibiting Both Mitochondrial Bioenergetics and Glycolysis Pathways and Retarding Cell Cycle Progression

Integr Cancer Ther. 2018 Mar;17(1):80-91. doi: 10.1177/1534735416684551. Epub 2016 Dec 23.

Abstract

Carnosine has been demonstrated to play an antitumorigenic role in certain types of cancer. However, its underlying mechanism is unclear. In this study, the roles of carnosine in cell proliferation and its underlying mechanism were investigated in the cultured human cervical gland carcinoma cells HeLa and cervical squamous carcinoma cells SiHa. The results showed that carnosine exerted a significant inhibitory effect on the proliferation of HeLa cells, whereas its inhibitory action on the proliferation of SiHa cells was much weaker. Carnosine decreased the ATP content through inhibiting both mitochondrial respiration and glycolysis pathways in cultured HeLa cells but not SiHa cells. Carnosine reduced the activities of isocitrate dehydrogenase and malate dehydrogenase in TCA (tricarboxylic acid) cycle and the activities of mitochondrial electron transport chain complex I, II, III, and IV in HeLa cells but not SiHa cells. Carnosine also decreased the mRNA and protein expression levels of ClpP, which plays a key role in maintaining the mitochondrial function in HeLa cells. In addition, carnosine induced G1 arrest by inhibiting the G1-S phase transition in both HeLa and SiHa cells. Taken together, these findings suggest that carnosine has a strong inhibitory action on the proliferation of human cervical gland carcinoma cells rather than cervical squamous carcinoma cells. Mitochondrial bioenergetics and glycolysis pathways and cell cycle may be involved in the carnosine action on the cell proliferation in cultured human cervical gland carcinoma cells HeLa.

Keywords: carnosine; cell cycle; human cervical cancer cells; isocitrate dehydrogenase; malate dehydrogenase; mitochondrial bioenergetics; mitochondrial electron transport chain (ETC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carnosine / pharmacology*
  • Cell Cycle / drug effects*
  • Cell Cycle / physiology
  • Cell Proliferation / drug effects
  • Energy Metabolism / drug effects
  • Energy Metabolism / physiology
  • Female
  • Glycolysis / drug effects
  • Glycolysis / physiology
  • HeLa Cells / drug effects
  • HeLa Cells / metabolism
  • HeLa Cells / pathology
  • HeLa Cells / physiology
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / physiopathology

Substances

  • Antineoplastic Agents
  • Carnosine