Plant-derived MINA-05 inhibits human prostate cancer proliferation in vitro and lymph node spread in vivo.
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 LNCaP-C4-2B 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 x and 2 x IC50 for PC-3 (P < .05 and P < .001, respectively), and at 1/2 x, 1 x, and 2 x 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 LNCaP-FGC (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 regrowth 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.
Vandyke
Kate
K
Oncology Research Centre, Prince of Wales Hospital, Barker Street, Randwick, NSW 2031, Australia.
White
Melanie Y
MY
Nguyen-Khuong
Terry
T
Ow
Kim
K
Luk
Sharon C-W
SC
Kingsley
Elizabeth A
EA
Rowe
Alexandra
A
Pang
Shiu-Fun
SF
Walsh
Bradley J
BJ
Russell
Pamela J
PJ
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D006131:Growth Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use*; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000473:pathology / Q000517:prevention & control*; D032141:Schisandra / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D004365:Drugs, Chinese Herbal; D006131:Growth Inhibitors