Plant-Derived MINA-05 Inhibits Human Prostate Cancer Proliferation In Vitro and Lymph Node Spread In Vivo

• Main Authors: Kate Vandyke, Melanie Y. White, Terry Nguyen-Khuong, Kim Ow, Sharon C.-W. Luk, Elizabeth A. Kingsley, Alexandra Rowe, Shiu-Fun Pang, Bradley J. Walsh, Pamela J. Russell
• Format: Article
• Language: English
• Published: Elsevier 2007-04-01
• Series: Neoplasia: An International Journal for Oncology Research
• Subjects: Prostate cancer; G2M block; MINA-05 herbal treatment; lymph node metastases; clonogenic assays
• Online Access: http://www.sciencedirect.com/science/article/pii/S1476558607801023
• ISSN: 1476-5586; 1522-8002

Few treatment options exist for metastatic prostate cancer (PC) that becomes hormone refractory (HRPC). In vitro, plant-derived MINA-05 caused dose-dependent decreases in cell numbers in HRPC cell lines LNCaPC4-2B and PC-3, and in androgen-sensitive LNCaP-FGC, DuCaP, and LAPC-4, by WST-1 assay. MINA-05 pretreatment significantly decreased clonogenic survival in agar and on plastic at 1 × and 2 × IC50 for PC-3 (P < .05 and P < .001, respectively), and at 1/2 ×, 1 ×, and 2 × IC50 for LNCaP-FGC cells (P < .001). MINA-05 also induced G2M arrest of LNCaP-FGC and PC-3 cells (by flow cytometry) and caused some apoptosis in LNCaPFGC (sub-G1, peak on flow, expression of activated caspase-3) but not in PC-3 cells. Western blotting indicated that these cell cycle changes were associated with decreased levels of regulatory proteins cyclin B1 and cdc25C. MINA-05 given daily by gavage for 39 days did not diminish primary orthotopic PC-3 growth in nude mice, but decreased the extent of lymph node invasion at higher doses. We conclude that MINA-05 induces G2M arrest, inhibits cell growth, reduces PC cell re-growth in vitro, and reduces lymph node invasion after orthotopic PC-3 cell implantation in vivo. It has potential as an adjuvant treatment for patients with PC.