Polyphyllin II inhibits thyroid cancer cell growth by simultaneously inhibiting glycolysis and oxidative

Jianwei Sun1, Ding Ding1, Qian Xiang2

  • 1Department of Ultrasound, Fifth Affiliated Hospital of Kunming Medical University, 17 South Goldenlake Rd., Gejiu, Yunnan, 661000, China.

PubMed
Abstract

Insights

Polyphyllin II effectively inhibits thyroid cancer cell growth by targeting both glycolysis and oxidative phosphorylation (OXPHOS). This dual-action approach suppresses proliferation, invasion, and migration while promoting apoptosis in cancer cells.

Area of Science:

  • Endocrinology
  • Oncology
  • Molecular Biology

Background:

  • Thyroid cancer is the most common endocrine malignancy with limited treatment options for metastatic disease.
  • Simultaneous targeting of glycolysis and oxidative phosphorylation (OXPHOS) is a novel cancer therapy strategy.
  • The metabolic effects of polyphyllin in thyroid cancer are currently unexplored.

Purpose of the Study:

  • To investigate the antitumor effects of polyphyllin compounds on thyroid cancer.
  • To elucidate the underlying mechanisms of polyphyllin's action in thyroid cancer cells.

Main Methods:

  • Thyroid cancer cells were treated with various polyphyllin compounds (I, II, VI, VII).
  • Assays included CCK-8 for viability, colony formation and EdU for proliferation, Transwell for invasion, and wound healing for migration.
  • Mechanisms investigated involved oxidative phosphorylation (OXPHOS) using extracellular oxygen consumption rate (OCR) assays, glycolysis via glucose uptake, lactate production, extracellular acidification rate (ECAR), and apoptosis detection through flow cytometry and western blotting.

Main Results:

  • Polyphyllin II demonstrated the most potent inhibition of thyroid cancer cell proliferation, invasion, and migration compared to other tested compounds.
  • Polyphyllin II significantly suppressed key metabolic pathways, including OXPHOS (reducing OCR, basal and maximal respiration, ATP-linked and spare respiration) and glycolysis (reducing glucose uptake, lactate production, and ECAR).
  • Polyphyllin II treatment also effectively induced apoptosis in thyroid cancer cells.

Conclusions:

  • Polyphyllin II exhibits significant antitumor activity against thyroid cancer by concurrently inhibiting both glycolysis and OXPHOS.
  • This dual metabolic targeting by Polyphyllin II suppresses cancer cell proliferation, invasion, and migration, while simultaneously inducing apoptosis.

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