Triptolide-induced apoptosis by inactivating nuclear factor-kappa B apoptotic pathway in multiple myeloma in vitro

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Multiple myeloma is a hematological malignancy characterized by uncontrolled proliferation of plasma cells.
• The nuclear factor-kappa B (NF-κB) signaling pathway plays a crucial role in multiple myeloma cell survival and drug resistance.
• Targeting the NF-κB pathway is a promising strategy for multiple myeloma treatment.

Purpose of the Study:

• To investigate the anti-proliferative and pro-apoptotic effects of triptolide on human multiple myeloma RPMI-8226 cells in vitro.
• To elucidate the role of the NF-κB signaling pathway, including NF-κB and IκBα, in mediating triptolide's effects.

Main Methods:

• Cell proliferation was assessed using the MTT assay.
• Apoptosis was detected via Hoechest 33258 staining and Annexin V/PI double staining.
• Western blot and confocal microscopy were employed to analyze the expression of NF-κB and IκBα.

Main Results:

• Triptolide demonstrated dose- and time-dependent inhibition of RPMI-8226 cell proliferation at nanomolar concentrations.
• Triptolide induced apoptosis in RPMI-8226 cells in a dose-dependent manner.
• Triptolide treatment led to the inhibition of NF-κB/p65 in the nuclear fraction and a corresponding increase in IκBα expression in the cytosol, indicating NF-κB pathway inactivation.

Conclusions:

• Triptolide exhibits significant anti-tumor activity against human multiple myeloma cells in vitro.
• The anti-cancer effects of triptolide are associated with the inactivation of the NF-κB signaling pathway.
• Triptolide represents a potential therapeutic agent for multiple myeloma targeting the NF-κB/p65 and IκBα axis.