Study on the mechanism of 17-Hydroxy-jolkinolide B on anaplastic thyroid cancer cell

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Anaplastic thyroid cancer (ATC) presents a poor prognosis with unconfirmed optimal treatments.
• Euphorbia fischeriana Steud possesses antitumor properties and has been used in cancer treatment.
• 17-Hydroxy-jolkinolide B (17-HJB), a plant-derived diterpenoid, has limited research regarding its anti-cancer effects.

Purpose of the Study:

• To investigate the anti-cancer effects of 17-Hydroxy-jolkinolide B (17-HJB) on anaplastic thyroid cancer (ATC).
• To elucidate the underlying mechanisms of 17-HJB's action, focusing on glucose metabolism and apoptosis.

Main Methods:

• Cell viability was assessed using MTT assays.
• Glucose consumption and lactate production were measured.
• Apoptosis was detected via Annexin V-FITC staining and flow cytometry.
• Western blotting was employed to analyze protein expression related to glycolysis and apoptosis.

Main Results:

• 17-HJB demonstrated dose-dependent inhibition of ATC cell viability.
• The compound suppressed glucose uptake and lactate production, downregulating key glycolytic enzymes (GLUT1, HK2, PFK1, PKM2).
• 17-HJB induced apoptosis in ATC cells, evidenced by increased Caspase-3 and cleaved Caspase-3 expression.
• In vivo studies confirmed 17-HJB's efficacy in inhibiting ATC tumor growth, consistent with in vitro findings.

Conclusions:

• 17-HJB exhibits significant anti-tumor activity against anaplastic thyroid cancer (ATC) both in vitro and in vivo.
• The mechanism involves the inhibition of aerobic glycolysis and glucose metabolism.
• 17-HJB effectively induces apoptosis in ATC cells, presenting a potential therapeutic strategy.