Experimental therapy of prostate cancer with novel natural product anti-cancer ginsenosides.
BACKGROUND
Ginseng and its components exert various biological effects, including antioxidant, anti-carcinogenic, anti-mutagenic, and anti-tumor activity, and recent research has focused on their value in human cancer prevention and treatment. We recently isolated 25-hydroxyprotopanaxadiol (25-OH-PPD) and 25-hydroxyprotopanaxatriol (25-OH-PPT) from Panax ginseng and evaluated their anti-cancer activity in vitro.


METHODS
We compared the effects of the two compounds on human prostate cancer LNCaP and PC3 cells in vitro and in a mouse PC3 xenograft tumor model. We also accomplished a preliminary determination of the mechanisms of action of the compounds.


RESULTS
25-OH-PPD, but not 25-OH-PPT, inhibited prostate cancer cell growth and proliferation, induced apoptosis, and led to arrest in the G1 phase of the cell cycle. In nude mice bearing PC3 xenograft tumors, 25-OH-PPD inhibited tumor growth in a dose-dependent manner and could be safely combined with chemotherapeutic agents (taxotere and gemcitabine) and radiation therapy to improve the anti-tumor effects. Further, in both PC3 and LNCaP cell lines, 25-OH-PPD increased expression of p21, p27, and Bax, induced PARP cleavage and activated caspases. The compound also reduced expression of MDM2, E2F1, Bcl2, cdk2/4/6, and cyclin D1, which correlated with the cell cycle arrest in G1 and the decrease in proliferation. Moreover, 25-OH-PPD demonstrated low toxicity to non-cancer cells and no observable host toxicity in animals either alone or in combination with conventional therapies.


CONCLUSIONS
The newly identified ginsenoside 25-OH-PPD may have potential as a novel prostate cancer therapeutic agent.
Wang
Wei
W
Department of Pharmacology and Toxicology and Division of Clinical Pharmacology, and Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Rayburn
Elizabeth R
ER
Hao
Miao
M
Zhao
Yuqing
Y
Hill
Donald L
DL
Zhang
Ruiwen
R
Wang
Hui
H
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000627:therapeutic use*; D017209:Apoptosis; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003131:Combined Modality Therapy; D005347:Fibroblasts / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D036145:Ginsenosides / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D023041:Xenograft Model Antitumor Assays
C529607:25-hydroxyprotopanaxadiol; C529606:25-hydroxyprotopanaxatriol; D000972:Antineoplastic Agents, Phytogenic; D036145:Ginsenosides