Anti-proliferative effects of paeonol on human prostate cancer cell lines DU145 and PC-3.
Paeonol (Pae) is the main active ingredient from the root bark of Paeonia moutan and the grass of Radix Cynanchi Paniculati. Numerous reports indicate that Pae effectively inhibits several types of cancer lines. In this study, we report that Pae hinders prostate cancer growth both in vivo and in vitro. Human prostate cancer lines DU145 and PC-3 were cultured in the presence of Pae. The xenograft tumor in mice was established by subcutaneous injection of DU145 cells. Cell growth was measured by MTT, and the apoptosis was detected by the flow cytometry. Expression of Bcl-2, Bax, Akt, and mTOR were tested by western blotting assay. DU145 and PC-3 showed remarkable sensitivity to Pae, and exposure to Pae induced dose-and time-dependent growth inhibitory responses. Moreover, treatment of Pae promoted apoptosis and enhanced activities of caspase-3, caspase-8, and caspase-9 in DU145. Further work demonstrated Pae reduced expression of Bcl-2 and increased expression of Bax in DU145. Interestingly, we observed that Pae significantly decreased phosphorylated status of Akt and mTOR, and inhibitory effects of Pae and PI3K/Akt inhibitor on DU145 proliferation were synergistic. Finally, we confirmed that oral administration of Pae to the DU145 tumor-bearing mice significantly lowered tumor cell proliferation and led to tumor regression. Pae possesses inhibitory effects on prostate cancer cell growth both in vitro and in vivo, and the anti-proliferative effect may be closely related to its activation of extrinsic and intrinsic apoptotic pathway and inhibition of the PI3K/Akt pathway.
Department of Urology, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China.
Yi
Y
Xu
Department of Urology, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China.
Jian-Yong
JY
Zhu
Department of Urology, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China.
Zhang-Ming
ZM
Lei
Department of Urology, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China.
Li-Jun
LJ
Wan
Department of Urology, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China.
Xiu-Wen
XW
Zhu
Department of Urology, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China.
Feng
F
Ye
Department of Urology, Quzhou People's Hospital, Quzhou, Zhejiang, 324000, China. Tongyyquzhou@sina.com.
Yan-Yue
YY
Tong
D027901:Acanthaceae / Q000737:chemistry; D000098:Acetophenones / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism / Q000627:therapeutic use*; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D019587:Dietary Supplements; D020834:Ethnopharmacology; D006801:Humans; D007408:Intestinal Absorption; D008297:Male; D008516:Medicine, Chinese Traditional; D008819:Mice, Nude; D029596:Paeonia / Q000737:chemistry; D024301:Plant Bark / Q000737:chemistry; D035261:Plant Components, Aerial / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D006109:Poaceae / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000097:blood / Q000178:diet therapy* / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays
D000098:Acetophenones; D000972:Antineoplastic Agents, Phytogenic; C013638:paeonol
Akt; Apoptosis; Caspases; Paeonol; Prostate cancer