Alpha-tomatine synergises with paclitaxel to enhance apoptosis of androgen-independent human prostate cancer PC-3 cells in vitro and in vivo

Lee, Sui-Ting, Wong, Pooi-Fong, Hooper, John David and Mustafa, Mohd Rais (2013) Alpha-tomatine synergises with paclitaxel to enhance apoptosis of androgen-independent human prostate cancer PC-3 cells in vitro and in vivo. Phytomedicine, 20 14: 1297-1305. doi:10.1016/j.phymed.2013.07.002


Author Lee, Sui-Ting
Wong, Pooi-Fong
Hooper, John David
Mustafa, Mohd Rais
Title Alpha-tomatine synergises with paclitaxel to enhance apoptosis of androgen-independent human prostate cancer PC-3 cells in vitro and in vivo
Journal name Phytomedicine   Check publisher's open access policy
ISSN 0944-7113
1618-095X
Publication date 2013-11-15
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.phymed.2013.07.002
Open Access Status Not Open Access
Volume 20
Issue 14
Start page 1297
End page 1305
Total pages 9
Place of publication Jena, Germany
Publisher Urban und Fischer Verlag
Language eng
Subject 3002 Drug Discovery
3004 Pharmacology
3003 Pharmaceutical Science
2707 Complementary and alternative medicine
1313 Molecular Medicine
Abstract Alpha (α)-tomatine, a major saponin found in tomato has been shown to inhibit the growth of androgen-independent prostate cancer PC-3 cells. The effects of α-tomatine in combination with the chemotherapeutic agent paclitaxel against PC-3 cells were investigated in the present study. Combined treatment with a sub-toxic dose of α-tomatine and paclitaxel significantly decreased cell viability with concomitant increase in the percentage of apoptotic PC-3 cells. The combined treatment, however, had no cytotoxic effect on the non-neoplastic prostate RWPE-1 cells. Apoptosis of PC-3 cells was accompanied by the inhibition of PI3K/Akt pro-survival signaling, an increase in the expression of the pro-apoptotic protein BAD but a decrease in the expressions of anti-apoptotic proteins, Bcl-2 and Bcl-xL. Results from a mouse xenograft model showed the combined treatment completely suppressed subcutaneous tumor growth without significant side effects. Consistent with its in vitro anti-cancer effects, tumor materials from mice showed increased apoptosis of tumor cells with reduced protein expression of activated PI3K/Akt. These results suggest that the synergistic anti-cancer effects of paclitaxel and α-tomatine may be beneficial for refractory prostate cancer treatment.
Keyword Alpha tomatine
Apoptosis
Paclitaxel
Tumor xenograft
Prostate cancer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Medicine Publications
 
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Created: Fri, 25 Apr 2014, 01:02:14 EST by Dominique Rossouw on behalf of Medicine - Mater Hospital