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Published on: August 23, 2019
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.
Background:
Thyroid cancer is the most common malignancy of the endocrine system, and effective treatments for metastatic disease are still lacking. Targeting both glycolysis and oxidative phosphorylation (OXPHOS) simultaneously represents a novel approach to cancer therapy. While polyphyllin has been shown to modulate cellular metabolism in various cancers, its role in thyroid cancer remains unexplored.
Purpose:
This study aimed to explore the antitumor effects and underlying mechanisms of polyphyllin in thyroid cancer.
Methods:
Thyroid cancer cells were treated with varying concentrations of Polyphyllin I, II, VI, and VII. Cell viability was assessed using the CCK-8 assay to identify the most effective polyphyllin compound and its optimal dosage. Colony formation and EdU incorporation assay were performed to evaluate cell proliferation, while Transwell assays were used to assess cell invasion. Cell migration ability was examined using the wound healing assay. The effect of Polyphyllin II on OXPHOS was evaluated using an extracellular oxygen consumption rate (OCR) assay kit. Glucose uptake, lactate production, glycolysis-related protein expression, and the extracellular acidification rate (ECAR) were measured to assess the effects of Polyphyllin II on glycolysis in thyroid cancer cells. Flow cytometry and western blotting were conducted to detect apoptosis.
Results:
Polyphyllin I, II, VI, and VII all inhibit the proliferation of thyroid cancer cells, with Polyphyllin II showing the most potent inhibitory effect. Polyphyllin II suppresses cell proliferation, invasion, and migration of thyroid cancer cells, while also promoting apoptosis. Mechanism studies reveal that Polyphyllin II inhibits extracellular OCR, basal respiration, maximum respiration, ATP-linked respiration, spare respiration capacity, glucose uptake, lactate production, glycolytic rate-limiting enzymes, and the ECAR in thyroid cancer cells.
Conclusion:
Polyphyllin II simultaneously inhibits glycolysis and OXPHOS, thereby suppressing the invasion, migration, and proliferation of thyroid cancer cells, while also promoting apoptosis.
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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