Caffeic acid phenethyl ester (CAPE), a honeybee propolis-derived bioactive ingredient, has not been extensively elucidated regarding its effect on prostate cancer and associated mechanisms. The mucosa-associated lymphoid tissue 1 gene (MALT1) modulates NF-κB signal transduction in lymphoma and non-lymphoma cells. We investigated the functions and regulatory mechanisms of CAPE in relation to MALT1 in prostate carcinoma cells. In p53- and androgen receptor (AR)-positive prostate carcinoma cells, CAPE downregulated AR and MALT1 expression but enhanced that of p53, thus decreasing androgen-induced activation of MALT1 and prostate-specific antigen expressions. p53 downregulated the expression of MALT in prostate carcinoma cells through the putative consensus and nonconsensus p53 response elements. CAPE downregulated MALT1 expression and thus inhibited NF-κB activity in p53- and AR-negative prostate carcinoma PC-3 cells, eventually reducing cell proliferation, invasion, and tumor growth in vitro and in vivo. CAPE induced the ERK/JNK/p38/AMPKα1/2 signaling pathways; however, pretreatment with the corresponding inhibitors of MAPK or AMPK1/2 did not inhibit the CAPE effect on MALT1 blocking in PC-3 cells. Our findings verify that CAPE is an effective antitumor agent for human androgen-dependent and -independent prostate carcinoma cells in vitro and in vivo through the inhibition of MALT1 expression via the AR/p53/NF-κB signaling pathways.

Functions of metallothionein 2A (MT2A) in bladder cancer have not been extensively explored even though metallothioneins are regarded as modulators in several biological regulations including oxidation and cancerous development. We evaluated MT2A in bladder carcinoma cells in terms of the mechanisms of regulation and the underlying functions. MT2A overexpression not only downregulated endogenous ROS but also blocked ROS induced by H₂O₂. We used the annexin V-FITC apoptosis assay to determine the modulation of H₂O₂-induced cell apoptosis by MT2A expression. Results of immunoblot and reporter assays indicated that caffeic acid phenethyl ester (CAPE) treatment induced MT2A and heme oxygenase-1 (HO-1) expressions; moreover, the involvement of CAPE in either upregulation of the HO-1 expression or downregulation of endogenous ROS is MT2A dependent in bladder carcinoma cells. Knockdown of MT2A increased invasion and cell growth in vitro and in vivo, whereas ectopic overexpression of MT2A had the reverse effect in bladder carcinoma cells. Unlike bladder cancer tissues, the real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) analysis showed a significant level of MT2A mRNA in the normal bladder tissues. Collectively, our results indicated that MT2A is acting as an antioxidant and also a tumor suppressor in human bladder carcinoma cells.

This study investigated and compared the surgical outcomes of using endoscopic enucleation (thulium: YAG laser and bipolar plasma; ThuLEP) with robotic-assisted simple prostatectomy (RASP) in the treatment of prostates larger than 80 cm³. Records were obtained for the period from January 2014 to December 2020 for selected patients with BPO who underwent RASP, ThuLEP, or bipolar transurethral enucleation of the prostate (B-TUEP). Patients were excluded if they had active malignant disease, neurogenic bladder, lower urinary tract syndrome for reasons other than BPO, and a history of prostate surgery. Data of 396 patients who underwent B-TUEP, ThuLEP, and RASP were examined. A total of 112 patients met the including criteria, 85 of whom (B-TUEP: 29; ThuLEP: 41; RASP: 15) completed the final visit. The mean operation time and duration of postoperative hospital stays in the RASP group were significantly longer than those of the B-TUEP and ThuLEP groups. Only 1 patient in the RASP group required blood transfusion. The RASP group was superior to the other groups in voiding improvement including Qmax and IPSS voiding score. The pain score of the ThuLEP group after surgery was significantly lower than that of the other two groups during hospitalization, whereas the QoL scores were identical between the three groups at 2 weeks, 3 months, and 6 months post operation. The rates of returning to ER within the first postoperative month did not differ significantly between the three groups, and all the reasons for return involved minor complications that required no additional invasive treatment. These three surgical methods (B-TUEP, ThuLEP, and RASP) are all effective and safe for treating prostates larger than 80 cm3, with each having its particular advantages. B-TUEP requires the shortest operation time, ThuLEP causes the lowest postoperative pain, and RASP results in superior voiding function improvement.

The WNT1 inducible signaling pathway protein 1 (WISP1), a member of the connective tissue growth factor family, plays a crucial role in several important cellular functions in a highly tissue-specific manner. Results of a RT-qPCR indicated that WISP1 expressed only in cells of the human prostate fibroblasts, HPrF and WPMY-1, but not the prostate carcinoma cells in vitro. Two major isoforms (WISP1v1 and WISP1v2) were identified in the HPrF cells determined by RT-PCR and immunoblot assays. The knock-down of a WISP1 blocked cell proliferation and contraction, while treating respectively with the conditioned medium from the ectopic WISP1v1- and WISPv2-overexpressed 293T cells enhanced the migration of HPrF cells. The TNFα induced WISP1 secretion and cell contraction while the knock-down of WISP1 attenuated these effects, although TNFα did not affect the proliferation of the HPrF cells. The ectopic overexpression of WISP1v1 but not WISP1v2 downregulated the N-myc downstream regulated 1 (NDRG1) while upregulating N-cadherin, slug, snail, and vimentin gene expressions which induced not only the cell proliferation and invasion in vitro but also tumor growth of prostate carcinoma cells in vivo. The results confirmed that WISP1 is a stroma-specific secreting protein, enhancing the cell migration and contraction of prostate fibroblasts, as well as the proliferation, invasion, and tumor growth of prostate carcinoma cells.

Peer reviewed article authored by (Hou CP, Lin YH, Chen CL, Chang PL, Tsui KH). Read article or submit your manuscript for publishing.