Regulation of signaling pathways involved in lupeol induced inhibition of proliferation and induction of apoptosis in human prostate cancer cells
Authors: Neetu Kalra
Yogeshwer Shukla
Nidhi Nigam
Sahdeo Prasad
Journal: Molecular carcinogenesis (2008)
Discipline: CLINICAL MEDICINE
Keywords: Prostate cancer; Lupeol; Cell proliferation; Cell death; Anticancer effects
Affiliations: Proteomics Laboratory, Indian Institute of Toxicology Research, Lucknow, India.

Abstract:  Prostate cancer (PCa) is the most frequently diagnosed noncutaneous cancer and the leading cause of cancer related deaths in men in the United States and many other Asian countries. Dietary factors are considered as a strategic agent to control the risk of PCa. Lupeol, a triterpene, present in fruits and medicinal plants, has been shown to possess many pharmacological properties including anticancer effects. Here, effect of lupeol on cell proliferation and cell death was evaluated using human PCa cells, PC-3. In MTT assay, lupeol inhibited the cell proliferation (12-71%) in dose (50-800 microM) and time dependent manner. Flow-cytometric analysis of cell-cycle revealed that an antiproliferative effect of lupeol (400-600 microM) is associated with an increase in G(2)/M-phase arrest (34-58%). RT-PCR analysis showed that lupeol-induced G2/M-phase arrest was mediated through the inhibition of cyclin regulated signaling pathway. Lupeol inhibited the expression of cyclin B, cdc25C, and plk1 but induced the expression of 14-3-3sigma genes. However no changes were observed in the expression of gadd45, p21(waf1/cip1) and cdc2 genes. Results of western blot showed that lupeol regulates the phosphorylation of cdc2 (Tyr15) and cdc25C (Ser198). Further, on increase of lupeol exposure to PC-3 cells an induction of apoptosis was recorded, which was associated with upregulation of bax, caspase-3, -9, and apaf1 genes and down regulation of antiapoptotic bcl-2 gene. The role of caspase-induced apoptosis was confirmed by increase in reactive oxygen species, loss of mitochondrial membrane potential followed by DNA fragmentation. Thus, our study suggests that lupeol possess novel antiproliferative and apoptotic potential against PCa. 

Retracted: Yes

PubPeer comments:
 Fig 4 (C): Indicated dote plots are more similar than one would expect. ![file] , 
 At right: Fig 4C. At left: Fig. 5(B) from [Shukla et al. (2007)] . ![file] Surprising similarity of panels, between experiments conducted with lupeol and with [6]-gingerol. , 
 Nice try Elegia. Its really funny to know that you gone through the whole paper carefully for potential problems and came up with this. If you look the dot plot carefully, you will find that there are lots of other events as well which are not at all similar. It seems that you never ever performed flow cytometry experiments. Look carefully the events outside the gated population, pattern is entirely different. Please stop discrediting other s work , 
 #3 * Nice try Elegia. Its really funny to know that you gone through the whole paper carefully for potential problems and came up with this. If you look the dot plot carefully, you will find that there are lots of other events as well which are not at all similar. It seems that you never ever performed flow cytometry experiments. Look carefully the events outside the gated population, pattern is entirely different. Please stop discrediting other s work * How could one discredit such perfection? ![file] And from the companion paper, [Shukla et al (2007)] , where the FACS plots result from [6-]gingerol rather than lupeol: ![] , 
 I have to agree with Elegia Verreauxii - the FACS plots in Figure 4C show unexpected similarities, both within as well as between panels. I found a couple more of those similarities, shown with colored boxes here: , 
 I have to agree with Elegia Verreauxii. The panels shown in Figure 4C show unexpected similarities, both within as well as between panels. Here is a new, marked version, with some more similarities as noted previously. ![file] , 
 2020 retraction. https: onlinelibrary.wiley.com doi abs 10.1002 mc.20442 The above article, published online on April 10 2008 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief and Wiley Periodicals, Ltd. The retraction has been agreed due to data duplication, both from previous papers from the same group (Shukla Y, Prasad S, Tripathi C, Singh M, George J, Kalra N. In vitro and in vivo modulation of testosterone mediated alterations in apoptosis related proteins by [6]u2010gingerol. Mol Nutr Food Res. 2007;51(12):1492u20131502. https: doi.org 10.1002 mnfr.200700197 as well as within the figures themselves, specifically figure 4u2009C, where the flow cytometry contains multiple intrau2010figure duplications. The authors and the institution were both contacted by the publisher for explanations regarding the duplication and both were unresponsive. Prasad S, Nigam N, Kalra N et al. Regulation of Signaling Pathways Involved in Lupeol Induced Inhibition of Proliferation and Induction of Apoptosis in Human Prostate Cancer Cells. Mol Carcinog. 2008; 916u2013924. https: doi.org 10.1002 mc.20442 ,