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      Qianlongtong Inhibits Proliferation and Induces Apoptosis of Hyperplastic Prostate Cells

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          Abstract

          Qianlongtong is a compound made from traditional Chinese herbs and it has proven to be very effective to treat patients with benign prostate hypertrophy. However, its mechanism is still unknown. This study is designed to investigate the effect of Qianlongtong on proliferation and apoptosis of hyperplastic prostate cells. Flow cytometry (FCM) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) were used to assess proliferation and apoptosis of hyperplastic prostate cells in the following groups: control group, tamoxifen group, and groups with low, moderate, and high dosage of Qianlongtong. Reverse transcription-polymerase chain reaction analysis was used to investigate the underlying mechanisms for increased apoptosis. Cells treated with Qianlongtong were mainly blocked in the G0/G1 phase. The apoptotic index of each group was significantly higher than that in the control group. The apoptotic index in the high- and moderate-dosage groups was similar to that in the tamoxifen group. The high- and moderate-dosage groups had lower Bcl-2 and higher Bax messenger RNA (mRNA) levels compared with the control group. Qianlongtong inhibits proliferation and promotes the apoptosis of hyperplastic prostate cells.

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          Most cited references25

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          Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage.

          An appropriate control over cell cycle progression depends on many factors. Cyclin-dependent kinase (CDK) inhibitor p21 (also known as p21(WAF1/Cip1)) is one of these factors that promote cell cycle arrest in response to a variety of stimuli. The inhibitory effect of P21 on cell cycle progression correlates with its nuclear localization. P21 can be induced by both p53-dependent and p53-independent mechanisms. Some other important functions attributed to p21 include transcriptional regulation, modulation or inhibition of apoptosis. These functions are largely dependent on direct p21/protein interactions and also on p21 subcellular localizations. In addition, p21 can play a role in DNA repair by interacting with proliferating cell nuclear antigen (PCNA). In this review, we will focus on the multiple functions of p21 in cell cycle regulation, apoptosis and gene transcription after DNA damage and briefly discuss the pathways and factors that have critical roles in p21 expression and activity.
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            G1 phase progression: cycling on cue.

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              Human cyclin E, a nuclear protein essential for the G1-to-S phase transition.

              Cyclin E was first identified by screening human cDNA libraries for genes that would complement G1 cyclin mutations in Saccharomyces cerevisiae and has subsequently been found to have specific biochemical and physiological properties that are consistent with it performing a G1 function in mammalian cells. Most significantly, the cyclin E-Cdk2 complex is maximally active at the G1/S transition, and overexpression of cyclin E decreases the time it takes the cell to complete G1 and enter S phase. We have now found that mammalian cells express two forms of cyclin E protein which differ from each other by the presence or absence of a 15-amino-acid amino-terminal domain. These proteins are encoded by alternatively spliced mRNAs and are localized to the nucleus during late G1 and early S phase. Fibroblasts engineered to constitutively overexpress either form of cyclin E showed elevated cyclin E-dependent kinase activity and a shortened G1 phase of the cell cycle. The overexpressed cyclin E protein was detected in the nucleus during all cell cycle phases, including G0. Although the cyclin E protein could be overexpressed in quiescent cells, the cyclin E-Cdk2 complex was inactive. It was not activated until 6 to 8 h after readdition of serum, 4 h earlier than the endogenous cyclin E-Cdk2. This premature activation of cyclin E-Cdk2 was consistent with the extent of G1 shortening caused by cyclin E overexpression. Microinjection of affinity-purified anti-cyclin E antibodies during G1 inhibited entry into S phase, whereas microinjection performed near the G1/S transition was ineffective. These results demonstrate that cyclin E is necessary for entry into S phase. Moreover, we found that cyclin E, in contrast to cyclin D1, was required for the G1/S transition even in cells lacking retinoblastoma protein function. Therefore, cyclins E and D1 control two different transitions within the human cell cycle.
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                Author and article information

                Journal
                Am J Mens Health
                Am J Mens Health
                JMH
                spjmh
                American Journal of Men's Health
                SAGE Publications (Sage CA: Los Angeles, CA )
                1557-9883
                1557-9891
                08 May 2018
                September 2018
                : 12
                : 5
                : 1548-1553
                Affiliations
                [1 ]Department of Andrology, First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, Hunan, China
                [2 ]Department of Pathology, Hunan University of Chinese Medicine, Changsha, Hunan, China
                Author notes
                [*]Xi Zhang, Department of Pathology, Hunan University of Chinese Medicine, 300 Xueshi Rd, Changsha, Hunan, 410208, China. Email: 1104622012@ 123456qq.com
                Article
                10.1177_1557988318772736
                10.1177/1557988318772736
                6142119
                29737939
                00a2d8b6-035a-42bc-b803-897e58506d62
                © The Author(s) 2018

                This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

                History
                : 8 January 2018
                : 2 March 2018
                : 7 March 2018
                Categories
                Original Articles

                qianlongtong,bph,apoptosis
                qianlongtong, bph, apoptosis

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