Cardiac and Cognitive Effects of Androgen Deprivation Therapy: Are They Real?

Quon, Harvey; Loblaw, D.A.

doi:10.3747/co.v17i0.698

Cited by 13 publications

(2 citation statements)

References 92 publications

(61 reference statements)

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“…Numerous studies have focused on the androgen ablation, by decreased testosterone synthesis and blockade of androgen receptor, as the major treatment for hormone-sensitive prostate cancer ( 35 , 36 ). Despite the androgen deprivation therapy in prostate cancer patients, prostatic DHT levels were found to be 25% of the pretreatment levels ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

Novel Molecular Targets of Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer

Mahapatra

Karnes

Holmes

et al. 2011

AAPS J

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Advanced prostate cancer has significant long-term morbidity, and there is a growing interest in alternative and complimentary forms of therapy that will improve the outcomes of patients. Azadirachta indica (common name: neem) contains multiple active compounds that have potent anti-inflammatory and anticancer properties. The present study investigates the novel targets of the anticancer activity of ethanol extract of neem leaves (EENL) in vitro and evaluates the in vivo efficacy in the prostate cancer models. Analysis of the components in the EENL by mass spectrometry suggests the presence of 2′,3′-dehydrosalannol, 6-desacetyl nimbinene, and nimolinone. Treatment of C4-2B and PC-3M-luc2 prostate cancer cells with EENL inhibited the cell proliferation. Genome-wide expression profiling, using oligonucleotide microarrays, revealed genes differentially expressed with EENL treatment in prostate cancer cells. Functional analysis unveiled that most of the up-regulated genes were associated with cell death, and drug metabolism, and the down-regulated genes were associated with cell cycle, DNA replication, recombination, and repair functions. Quantitative PCR confirmed significant up-regulation of 40 genes and immunoblotting revealed increase in the protein expression levels of HMOX1, AKR1C2, AKR1C3, and AKR1B10. EENL treatment inhibited the growth of C4-2B and PC-3M-luc2 prostate cancer xenografts in nude mice. The suppression of tumor growth is associated with the formation of hyalinized fibrous tumor tissue and the induction of cell death by apoptosis. These results suggest that EENL-containing natural bioactive compounds could have potent anticancer property and the regulation of multiple cellular pathways could exert pleiotrophic effects in prevention and treatment of prostate cancer.Electronic supplementary materialThe online version of this article (doi:10.1208/s12248-011-9279-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Novel Molecular Targets of Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer

Mahapatra

Karnes

Holmes

et al. 2011

AAPS J

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“…4 The treatment for patients who are not suitable for surgical intervention is androgen deprivation (Castration). 5 However, androgen deprivation treatment was reported to have long-term adverse effects, and was not curative for androgenindependent prostate cancer in 70-80% of the total number of patients, 6,7 i.e. castration-resistant prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

<p>The Effects of Matrine in Combination with Docetaxel on Castration-Resistant (Androgen-Independent) Prostate Cancer</p>

Li¹,

Xu²,

He³

et al. 2019

CMAR

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Background: Matrine (MAT) exhibits higher efficacy of chemotherapy when it is combined with other chemotherapeutic drugs; however, the therapeutic efficacy of matrine in combination with docetaxel (DOC) for prostate cancer, or even androgen-independent prostate cancer, remains poorly understood and the underlying molecular mechanisms have not yet been clearly defined. In the present study, we investigated whether matrine combined with docetaxel can strengthen anti-cancer effect. Methods: In this study, 7 groups were established, including (1) blank control group (cells).(2) 0.1 g/L MAT group, (3) 0.5 g/L MAT group, (4) 0.1 g/L MAT+ 50 μg/L DOC group, (5) 0.5 g/L MAT+ 50 μg/L DOC group, (6) 0.1 g/L MAT+ 100 μg/L DOC group, and (7) 0.5 g/L MAT+ 100 μg/L DOC group. MTS assay was performed to detect the anti-proliferative effects of each group on DU145 and PC-3 cells. At the same time, Transwell assay was performed to detect anti-migrative and anti-invasive effects of each group on DU145 and PC-3 cells. Biochemical colorimetric method and enzyme-linked immunosorbent assay were performed to detect the levels of LDH, IL-1β and IL-18 of each group on DU145 and PC-3 cells. Flow cytometry (FCM) assay was used to do the apoptosis analysis on DU145 and PC-3 cells of each group. At last, Western blot analysis was performed to investigate the expression levels of caspase1 in cells of each group. Statistical analyses were performed with SPSS 17.0 (SPSS Inc, USA) software, and one-way ANOVA and Fisher's exact test was taken. Results: MTS assay showed that matrine combined with docetaxel could inhibit both DU145 and PC-3 cells' proliferation in a dose-and time-dependent manner. Transwell assay showed that matrine combined with docetaxel could inhibit both DU145 and PC-3 cells' migration and invasion in a dose-and time-dependent manner. The levels of LDH, IL-1β and IL-18 of matrine combined with docetaxel-treated DU145 and PC-3 cells were significantly increased, compared with the untreated control cells. Flow cytometry, as well as Annexin-V/PI staining, showed a significant and dose-dependent increase in the number of early, as well as late-stage apoptotic cells in both DU145 and PC-3 cells compared with the untreated control cells. Western blot analysis showed that matrine combined with docetaxel treatment led to the expression of caspase1 in both DU145 and PC-3 cells. Conclusion: It may be more effective to use matrine in combination with docetaxel to treat androgen-resistant prostate cancer because matrine can help to affect proliferation, migration, invasion, apoptosis, metabolism, and have anti-inflammation effect on the tumor cells.

Cardiac and Cognitive Effects of Androgen Deprivation Therapy: Are They Real?

Cited by 13 publications

References 92 publications

Novel Molecular Targets of Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer

Novel Molecular Targets of Azadirachta indica Associated with Inhibition of Tumor Growth in Prostate Cancer

<p>The Effects of Matrine in Combination with Docetaxel on Castration-Resistant (Androgen-Independent) Prostate Cancer</p>

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