Curcumin impacts on cisplatin sensitivity determining apoptotic boost in mesothelioma

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Cancer remains a leading cause of global mortality, with chemotherapy facing limitations like severe side effects and drug resistance.
• Malignant mesothelioma (MM), an aggressive asbestos-related cancer, has a poor prognosis despite current treatments like cisplatin-based chemotherapy.
• Polyphenols, such as curcumin, are being investigated as alternative cancer therapies due to their anticancer properties and potential synergistic effects with standard drugs.

Purpose of the Study:

• To evaluate the efficacy of a standardized curcumin extract in enhancing cisplatin sensitivity in malignant mesothelioma (MM).
• To investigate the molecular mechanisms underlying the combined effect of curcumin and cisplatin in MM cell lines.

Main Methods:

• Utilized two MM cell lines (MSTO-211H and Ist-Mes2) in 2D and 3D culture models.
• Assessed the effects of combined curcumin and cisplatin treatment on apoptosis, Nrf2, and NUPR1.
• Analyzed treatment response in cell lines with varying sensitivity to piroxicam/cisplatin.

Main Results:

• The combined curcumin and cisplatin treatment significantly increased apoptosis in MM cells.
• This enhanced cell death was associated with the inactivation of Nrf2, a transcription factor crucial in carcinogenesis.
• Concomitant inactivation of NUPR1, a regulator involved in chemoresistance, was also observed.

Conclusions:

• A standardized curcumin extract can enhance the sensitivity of malignant mesothelioma cells to cisplatin chemotherapy.
• The combination therapy shows promise by inducing apoptosis through the inactivation of Nrf2 and NUPR1.
• This approach offers a potential strategy to improve MM treatment outcomes.