Frontiers in pharmacology · 2026
Bruceine D attenuates prostate cancer growth and motility by suppressing PI3K/AKT signaling and downregulating CXCL16: implications for skeletal metastasis in orthopedic oncology.
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Chen Zhiwei, Huang Qingbin, Zheng Yingming, Garu A, LingHu Xitao, Yu Wenchong, Zhao Guangquan, Zhang Jieying, Tian Lin, Tang Yubo, Huang Shuai, Zhao Xiaodong
Аннотация
INTRODUCTION: Prostate cancer often reaches bone, which poses a challenge in orthopedic oncology since few therapies directly suppress tumor growth in bone. Bruceine D (BD) is a quassinoid from Brucea javanica. It is known anticancer activity but its effects on prostate cancer have not been defined.
METHODS: In this paper, we studied BD's drug effects on PC-3 and C4-2B prostate cancer cells using CCK-8, colony formation, wound healing, and Transwell assays. We measured apoptosis by Annexin V-FITC/PI staining and flow cytometry. RNA sequencing, Western Blotting and molecular docking were used to identify signaling pathways and potential targets. We evaluated BD's antitumor effects and toxicities in a subcutaneous xenograft model in nude mice.
RESULTS: BD inhibited proliferation, migration, invasion and induced apoptosis in prostate cancer cells in a time- and dose-dependent manner. Transcriptomic analysis showed BD downregulated PI3K/AKT pathway components (PIK3AP1, PIK3C2B, PIK3CB, PIK3R2, AKT1) and CXCL16. Western blotting showed decreased expression of p-PI3K, p-AKT, PCNA, MMP9, CXCL16, BCL-2 and BAX. Molecular docking predicted favorable binding to these targets. BD (0,0.7 mg/kg) reduced tumor volume by 87.4% without liver/kidney toxicity, and reduced Ki-67, PCNA, MMP9, CXCL16 in tumors.
CONCLUSION: BD reduced prostate cancer growth and motility by inhibiting PI3K/AKT signaling and concomitantly downregulating CXCL16, and showed anti-tumor activity in a subcutaneous xenograft model with good safety. These results provide mechanistic information on skeletal metastasis in orthopedic oncology. Dedicated bone metastasis models need to be evaluated.
METHODS: In this paper, we studied BD's drug effects on PC-3 and C4-2B prostate cancer cells using CCK-8, colony formation, wound healing, and Transwell assays. We measured apoptosis by Annexin V-FITC/PI staining and flow cytometry. RNA sequencing, Western Blotting and molecular docking were used to identify signaling pathways and potential targets. We evaluated BD's antitumor effects and toxicities in a subcutaneous xenograft model in nude mice.
RESULTS: BD inhibited proliferation, migration, invasion and induced apoptosis in prostate cancer cells in a time- and dose-dependent manner. Transcriptomic analysis showed BD downregulated PI3K/AKT pathway components (PIK3AP1, PIK3C2B, PIK3CB, PIK3R2, AKT1) and CXCL16. Western blotting showed decreased expression of p-PI3K, p-AKT, PCNA, MMP9, CXCL16, BCL-2 and BAX. Molecular docking predicted favorable binding to these targets. BD (0,0.7 mg/kg) reduced tumor volume by 87.4% without liver/kidney toxicity, and reduced Ki-67, PCNA, MMP9, CXCL16 in tumors.
CONCLUSION: BD reduced prostate cancer growth and motility by inhibiting PI3K/AKT signaling and concomitantly downregulating CXCL16, and showed anti-tumor activity in a subcutaneous xenograft model with good safety. These results provide mechanistic information on skeletal metastasis in orthopedic oncology. Dedicated bone metastasis models need to be evaluated.