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Local anesthetics induce apoptosis in human thyroid cancer cells through the mitogen-activated protein kinase pathway

Yuan-Ching Chang1, Yi-Chiung Hsu2, Chien-Liang Liu3

  • 1Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan ; Department of Surgery, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan ; Mackay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan.

Plos One
|March 4, 2014
PubMed

Insights

Local anesthetics like lidocaine and bupivacaine show cytotoxic effects on thyroid cancer cells. These agents induce apoptosis and necrosis, offering potential new benefits for thyroid cancer management.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Local anesthetics are commonly used in thyroid procedures.
  • Emerging evidence suggests local anesthetics possess anti-cancer properties, including inhibiting cell proliferation and inducing apoptosis.
  • Their specific effects on thyroid cancer cells remain largely unexplored.

Purpose of the Study:

  • To investigate the cytotoxic effects of lidocaine and bupivacaine on human thyroid cancer cell lines.
  • To elucidate the underlying molecular mechanisms, including apoptosis induction and signaling pathway involvement.

Main Methods:

  • Treatment of 8505C and K1 thyroid cancer cells with varying concentrations of lidocaine and bupivacaine.
  • Assessment of cell viability, colony formation, apoptosis, and necrosis using flow cytometry.
  • Analysis of mitochondrial membrane potential, cytochrome c release, caspase activation, PARP cleavage, and Bax/Bcl-2 ratio.
  • Microarray and pathway analysis to identify transcriptional changes.
  • Investigation of mitogen-activated protein kinase (MAPK) pathway activation (ERK1/2, p38 MAPK, JNK).

Main Results:

  • Lidocaine and bupivacaine significantly decreased cell viability and colony formation in a dose-dependent manner.
  • Both anesthetics induced apoptosis and, at higher concentrations, necrosis.
  • Mitochondrial pathway activation (cytochrome c release, altered Bax/Bcl-2 ratio) and caspase cascade activation (caspase 3/7, PARP cleavage) were observed.
  • Microarray analysis identified apoptosis as a key transcriptional response.
  • Extracellular signal-regulated kinase 1/2 (ERK1/2) activity was attenuated, while p38 MAPK and c-jun N-terminal kinase (JNK) were activated.
  • Inhibition of MAPK/ERK kinase and p38 MAPK pathways reduced caspase activation and PARP cleavage.

Conclusions:

  • Local anesthetics, specifically lidocaine and bupivacaine, exhibit significant cytotoxic effects on thyroid cancer cells.
  • These effects are mediated through the induction of apoptosis via mitochondrial pathways and modulation of MAPK signaling.
  • The findings suggest potential, previously unrecognized clinical benefits of local anesthetics in managing thyroid cancer.

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