Theaflavins induce G2/M arrest by modulating expression of p21waf1/cip1, cdc25C and cyclin B in human prostate carcinoma PC-3 cells
Authors: Preeti Roy
Sahdeo Prasad
Neetu Kalra
Yogeshwer Shukla
Jaspreet Kaur
Journal: Life Sciences (2007)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: Prostate cancer; Black tea polyphenol; Theaflavin; Cell proliferation; Cell death
Affiliations: Environmental Carcinogenesis Division, Industrial Toxicology Research Centre, Mahatma Gandhi Marg, Lucknow 226001, India.

Abstract:  Cancer of the prostate gland (PCA) is the most common invasive malignancy and is the second leading cause of cancer-related death in males. The polyphenolic constituents of black tea have gained considerable attention as chemopreventive agents. Many studies have shown that black tea reduces the risk of several cancer types. In the present study, we studied the effect of a black tea polyphenol, theaflavin (TF), on cellular proliferation and cell death in the human prostate cancer cell line, PC-3. We showed that TF inhibits cell proliferation in a dose- and time-dependent manner. Studies on cell cycle progression have shown that the anti-proliferative effect of TF is associated with an increase in the G2/M phase of PC-3 cells. Western blot results showed that TF-induced G2/M phase arrest was mediated through the inhibition of cyclin-regulated signaling pathways. TF induces cyclin kinase inhibitor p21(waf1/cip1) expression and inhibits cdc25C and cyclin B expression. Increased exposure time to TF caused apoptosis of PC-3 cells, which was associated with up-regulation of the pro-apoptotic proteins Bax, caspase-3 and caspase-9 and down-regulation of anti-apoptotic protein Bcl-2. The role of caspase-induced apoptosis was further confirmed by a reduction in mitochondria membrane potential and the appearance of a DNA laddering pattern. Thus, it can be concluded that TF acts as an effective anti-proliferative agent by modulating cell growth regulators in prostate cancer cells. 

Retracted: No

PubPeer comments:
 b-actin from two different papers are more similar than one would expect; treatments and cells are different. 10.1016 j.lfs.2007.07.033 Fig 4 (B): Effect of theaflavin on PC-3 prostate cancer cells. 10.1016 j.lfs.2007.11.006 Fig 5 (B): Effect of resveratrol on mouse skin tumors ![file] , 
 ![file] , 
 #1  b-actin from two different papers are more similar than one would expect; treatments and cells are different. ![] The same band was also used as loading control for a **third** set of conditions in Fig 1B of  Resveratrol enhances ultraviolet B-induced cell death through nuclear factor-kappaB pathway in human epidermoid carcinoma A431 cells [(Roy et al 2009)] . ![file] , 
 Two more overlaps between beta-actin bands from the present Fig 4B *[left]* and Fig 1B from [Roy et al (2009)] . Controlling for (respectively) varying levels of theaflavins; and varying combinations of resveratrol + UVB. ![file] UPDATE: One more comparison, this time with a panel from Fig 3B of  Induction of apoptosis by tea polyphenols mediated through mitochondrial cell death pathway in mouse skin tumors [(Roy et al 2009b)] *[at bottom]*. Enhanced by a 300% vertical stretch. ![file] , 
 ![file] H t Ash Paul https: twitter.com pash22 status 1165511075170795522 , 
 Retracted [6 August 2022] . After four years. ------------------ This article has been retracted at the request of the Editor-in-Chief. Portions of Fig. 2 of the article are almost identical to Fig. 5 (B) of the article published by the same group in *Life Sciences*, 82, (2007) 348u2013358, https: doi.org 10.1016 j.lfs.2007.11.006, this band is also repeatedly used in Fig. 1 (B) published by the same group in *Biochemical and Biophysical Research Communications*, 384, (2009) 215u2013220, https: doi.org 10.1016 j.bbrc.2009.04.100. Fig. 4B contains similar part to Fig. 1B in a paper published by the same group in *Cancer Biology Therapy*, 8, (2009) 1281u20131287, https: doi.org 10.4161 cbt.8.13.8728. Fig. 4B is also very similar to Fig. 4B of the article published by the same group in *Biochemical and Biophysical Research Communications*, 384, (2009) 215u2013220, https: doi.org 10.1016 j.bbrc.2009.04.100. The authors have not been able to provide any justification for this image manipulation. ,