Multidimensional approaches in dealing with prostate cancer

Ali, Safdar; Ali, Sher

doi:10.1016/j.gene.2007.11.020

Cited by 4 publications

(5 citation statements)

References 77 publications

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“…Because AR is the main driving force for growth of both hormone-dependent and castration-resistant prostate cancer cells, 3 – 5 we performed studies in vitro to determine whether AR levels are affected by RO in these cells. In addition, we examined whether RO might also influence levels of ERβ, which is a suppressor of tumor cell growth.…”

Section: Resultsmentioning

confidence: 99%

“…However, although a number of antihormonal treatment strategies are currently employed to control progression of the disease, drug-resistant tumors frequently emerge. 4 , 5 Cancers that become nonresponsive to antihormone therapy are termed castration-resistant, even though AR still plays a role in these tumors. 28 Patients with antihormone-resistant tumors have a poor prognosis, 29 , 30 and, because treating such tumors is so challenging, new ways to control this type of disease are urgently sought.…”

Section: Discussionmentioning

confidence: 99%

“… 4 Human prostate cancer cells often proliferate in response to endogenous or exogenous androgens and estrogens, which also inhibit cell death and promote metastasis. 5 Whereas chemical castration, in the form of systemic exposure to chemotherapeutic drugs or antihormones, is the standard treatment for primary prostate cancer, drug-resistant cancer cells often emerge, limiting the usefulness of continued chemotherapy. 5 In addition, many patients suffering from prostate cancer fail to respond to any form of hormonal therapy, leading to poor clinical prognosis.…”

Section: Introductionmentioning

confidence: 99%

“… 5 Whereas chemical castration, in the form of systemic exposure to chemotherapeutic drugs or antihormones, is the standard treatment for primary prostate cancer, drug-resistant cancer cells often emerge, limiting the usefulness of continued chemotherapy. 5 In addition, many patients suffering from prostate cancer fail to respond to any form of hormonal therapy, leading to poor clinical prognosis. As a consequence, novel, less toxic, and more effective treatments for prostate cancer are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

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Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

Liang

Mafuvadze

Aebi

et al. 2016

OTT

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Standard treatment for primary prostate cancer includes systemic exposure to chemotherapeutic drugs that target androgen receptor or antihormone therapy (chemical castration); however, drug-resistant cancer cells generally emerge during treatment, limiting the continued use of systemic chemotherapy. Patients are then treated with more toxic standard therapies. Therefore, there is an urgent need for novel and more effective treatments for prostate cancer. The cholesterol biosynthetic pathway is an attractive therapeutic target for treating endocrine-dependent cancers because cholesterol is an essential structural and functional component of cell membranes as well as the metabolic precursor of endogenous steroid hormones. In this study, we have examined the effects of RO 48-8071 (4′-[6-(allylmethylamino)hexyloxy]-4-bromo-2′-fluorobenzophenone fumarate; Roche Pharmaceuticals internal reference: RO0488071) (RO), which is an inhibitor of 2, 3-oxidosqualene cyclase (a key enzyme in the cholesterol biosynthetic pathway), on prostate cancer cells. Exposure of both hormone-dependent and castration-resistant human prostate cancer cells to RO reduced prostate cancer cell viability and induced apoptosis in vitro. RO treatment reduced androgen receptor protein expression in hormone-dependent prostate cancer cells and increased estrogen receptor β (ERβ) protein expression in both hormone-dependent and castration-resistant prostate cancer cell lines. Combining RO with an ERβ agonist increased its ability to reduce castration-resistant prostate cancer cell viability. In addition, RO effectively suppressed the growth of aggressive castration-resistant human prostate cancer cell xenografts in vivo without any signs of toxicity to experimental animals. Importantly, RO did not reduce the viability of normal prostate cells in vitro. Our study is the first to demonstrate that the cholesterol biosynthesis inhibitor RO effectively suppresses growth of human prostate cancer cells. Our findings suggest that cholesterol biosynthesis inhibitors such as RO, when used in combination with commonly used chemotherapeutic drugs or ERβ specific ligands, could represent a novel therapeutic approach to prevent the growth of prostate cancer tumors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

Liang

Mafuvadze

Aebi

et al. 2016

OTT

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“…Prostate cancer is one of the most common cancers affecting the male population globally. It is rated the second leading cause of cancer death among males in the USA, and the most commonly diagnosed non-cutaneous malignancy (Ali and Ali 2008 ; Pruthi et al 2006 ). In Southern African men, prostate cancer has an incidence of 40.5 per 100 000 of the population per year, and a mortality rate of 22.5 per 100 000 per year (Parkin et al 2005 ).…”

Section: Introductionmentioning

confidence: 99%

Knowledge of prostate cancer among males attending a urology clinic, a South African study

et al. 2015

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BackgroundIn South Africa, the rate of histologically diagnosed prostate cancer is 40.1 per 100 000 in whites and 14 per 100 000 in blacks. However, blacks have limited access to diagnostic facilities and present late with an advanced disease. Knowledge about prostate cancer in the South African male population is necessary in order to increase the acceptance of early prostate cancer screening.ObjectiveThis study assessed the knowledge of prostate cancer among men attending the urology outpatient clinic at a tertiary hospital in South Africa.MethodsA cross-sectional study was conducted from February to March 2010. A structured questionnaire was administered to participants using consecutive sampling of eligible patients and consisted of sections on sociodemographic details and knowledge about prostate cancer. A total of 346 males, 35 years of age and older, participated in the study.ResultsThe majority of the respondents (n = 258; 75.0%) were black, married (n = 220; 64.0%), from the Free State Province (n = 320; 92.8%), and had access to television (n = 248; 71.7%). Only 38 (11.0%) knew the three main symptoms and signs associated with prostate cancer. Level of school education, race and language were statistically significantly associated with level of knowledge whereas age and marital status were not.ConclusionMore than half (54.4%) of the respondents had not heard of prostate cancer. The majority of men who had heard of prostate cancer had a moderate level of knowledge. The factors significantly associated with level of knowledge need to be considered in educational campaigns, prostate cancer screening and treatment.

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Molecular mechanisms of TRP regulation in tumor growth and metastasis

Gkika

Prevarskaya

2009

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

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Transient Receptor Potential (TRP) channels modulate intracellular Ca2+ concentrations, consequently affecting both cell death and proliferation. It is not, therefore, surprising that the membrane expression of some TRP channels is altered during tumor growth and metastasis. These variations in channel abundance are due to TRP regulation on the transcriptional, translational, and targeting levels. This article mainly reviews the transcriptional mechanisms modulating TRP expression during tumorigenesis, involving hormones, growth factors, and alternative splicing.

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Multidimensional approaches in dealing with prostate cancer

Cited by 4 publications

References 77 publications

Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

Cholesterol biosynthesis inhibitor RO 48-8071 suppresses growth of hormone-dependent and castration-resistant prostate cancer cells

Knowledge of prostate cancer among males attending a urology clinic, a South African study

Molecular mechanisms of TRP regulation in tumor growth and metastasis

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