Cyclovirobuxine D suppresses cancer stemness in osteosarcoma with implication of the noncanonical NF-kappaB pathway

Area of Science:

• Pharmacology
• Oncology
• Molecular Biology

Background:

• Cyclovirobuxine D (CVB-D), a Buxus microphylla alkaloid, shows anticancer activity but its effects on osteosarcoma are unknown.
• Osteosarcoma remains a significant challenge with limited therapeutic options.

Purpose of the Study:

• To investigate the efficacy of CVB-D in osteosarcoma.
• To elucidate the underlying molecular mechanisms of CVB-D action in osteosarcoma.

Main Methods:

• Drug screening and cell viability assays (CCK-8, colony formation) on osteosarcoma cell lines.
• Flow cytometry for apoptosis and cell cycle analysis; RNA-sequencing for pathway identification (NF-kappaB).
• Assessment of cancer stemness markers and validation in a xenograft mouse model.

Main Results:

• CVB-D significantly suppressed osteosarcoma cell proliferation and stemness.
• Induction of apoptosis was observed in treated osteosarcoma cells.
• The non-canonical NF-kappaB pathway (p-NF-kappaB2/NF-kappaB2) was implicated, with effects reversible upon pathway activation.

Conclusions:

• CVB-D demonstrates potent anti-osteosarcoma activity.
• The non-canonical NF-kappaB pathway is a key mediator of CVB-D's effects.
• CVB-D represents a promising therapeutic candidate for osteosarcoma treatment.