Diosgenin, a steroidal sapogenin, obtained from Trigonella foenum-graecum, Dioscorea, and Rhizoma polgonati, has shown high potential and interest in the treatment of various cancers such as oral squamous cell carcinoma, laryngeal cancer, esophageal cancer, liver cancer, gastric cancer, lung cancer, cervical cancer, prostate cancer, glioma, and leukemia. This article aims to provide an overview of the in vivo, in vitro, and clinical studies reporting the diosgenin's anticancer effects. Preclinical studies have shown promising effects of diosgenin on inhibiting tumor cell proliferation and growth, promoting apoptosis, inducing differentiation and autophagy, inhibiting tumor cell metastasis and invasion, blocking cell cycle, regulating immunity and improving gut microbiome. Clinical investigations have revealed clinical dosage and safety property of diosgenin. Furthermore, in order to improve the biological activity and bioavailability of diosgenin, this review focuses on the development of diosgenin nano drug carriers, combined drugs and the diosgenin derivatives. However, further designed trials are needed to unravel the diosgenin's deficiencies in clinical application.
Male ; Humans ; Carcinoma, Squamous Cell/drug therapy* ; Diosgenin/metabolism* ; Mouth Neoplasms/drug therapy* ; Apoptosis ; Prostatic Neoplasms/drug therapy*

Cyclooxygenase-2 (Cox-2) is over-expressed in prostate cancer (PCa) and involved in its development and progression by facilitating inflammatory response, reducing cell apoptosis, increasing angiogenesis and damaging DNA oxidation. Selective Cox-2 inhibitors suppress PCa growth through various channels and therefore have a promising application value in the management of prostate cancer.
Apoptosis ; Cyclooxygenase 2 ; metabolism ; Cyclooxygenase 2 Inhibitors ; therapeutic use ; Humans ; Male ; Prostatic Neoplasms ; drug therapy ; metabolism

Androgens ; metabolism ; Antineoplastic Agents, Hormonal ; therapeutic use ; Humans ; Integrative Medicine ; Male ; Medicine, Chinese Traditional ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology

Skeletal metastases result in significant morbidity and mortality. This is particularly true of cancers with a strong predilection for the bone, such as breast, prostate, and lung cancers. There is currently no reliable cure for skeletal metastasis, and palliative therapy options are limited. The Wnt signaling pathway has been found to play an integral role in the process of skeletal metastasis and may be an important clinical target. Several experimental models of skeletal metastasis have been used to find new biomarkers and test new treatments. In this review, we discuss pathologic process of bone metastasis, the roles of the Wnt signaling, and the available experimental models and treatments.
Animals ; Bone Neoplasms ; drug therapy ; metabolism ; radiotherapy ; secondary ; surgery ; Breast Neoplasms ; metabolism ; pathology ; Disease Models, Animal ; Drug Delivery Systems ; Female ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Prostatic Neoplasms ; metabolism ; pathology ; Wnt Proteins ; metabolism ; Wnt Signaling Pathway ; beta Catenin ; metabolism

OBJECTIVETo study the clinicopathological characteristics of primary Non-Hodgkin's Lymphoma (NHL) of the prostate.

METHODSTwo cases of primary NHL of the prostate were studied by analyzing the clinical data, pathological features, prognosis and review of the literature.

RESULTSHE showed that the normal prostatic tissues were replaced by diffuse-type cancer tissues composed of oval or round medium- to large- size lymphoid cells, with vesicular nuclei, fine chromatin, 2-4 membrane-bound nucleoli and scanty cytoplasm, with either amphophilic or basophilic. Immunohistochemistry revealed: CD20 +, CD79a +, CD10 -, CD5 -, CD3 - and CD45 - in Case 1 and CD20+ + +, PSA +/-, CKpan -, Syn -, CgA -, 34betaE12 -, P504S - and CD3 - in Case 2. Case 1 received chemotherapy combined with radiotherapy, relapsed 4 years later and stabilized by repeated chemotherapy. Case 2 experienced no recurrence after treated by chemotherapy.

CONCLUSIONSurgical treatment could be avoided by preoperative pathological diagnosis of primary NHL of the prostate, for which combined chemotherapy should be the first preference.

Aged ; Antigens, CD20 ; analysis ; Follow-Up Studies ; Humans ; Immunohistochemistry ; Lymphoma, Non-Hodgkin ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Prognosis ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology

BACKGROUNDEpidemiological studies have shown that lycopene has anti-prostate cancer effect. In vitro tests also confirmed that it can promote apoptosis of prostate cancer cells. We investigated the effect of whole-tomato supplement lycopene on the prostate-specific antigen velocity in selected prostate cancer patients.

METHODSTwenty selected prostate cancer patients were given whole-tomato supplement lycopene 10 mg per day for about 6 months. Blood samples of patients were collected weekly to measure serum prostate-specific antigen (PSA) values. PSA velocity slope, which reflects the change of PSA, and the degree of change were also calculated. By comparing the values of average PSA velocity slope (rise or fall of PSA) before and after the administration of lycopene, the effect of lycopene can be evaluated. Blood chemistry analysis was regular followed as safety control.

RESULTSThree patients in the research group withdrew within 3 weeks because of inability to conform. The rest 17 patients continued for an average period of 6 months. Two patients withdrew because of cancer progression (PSA rise) who later received active treatment. The average fall in PSA was equivalent to 2.56% over (i.e. an average slope/d of -0.000 28) the first 3 months. In the last 3 months, average fall in PSA was equivalent to 31.58% (i.e. an average slope/d of -0.003 51). The Wilcoxon rank-sum test showed a statistically significant decrease of PSA velocity slope overall (P = 0.000 9). Analysis of the PSA doubling time (pre- vs. post-treatment) showed a median increase over 3 months but this was not statistically significant (P = 0.21). No toxic side effect was observed during the whole process. The results indicate that the average PSA change is "decline" in patients, and the degree of the decline is accelerated.

CONCLUSIONAdministration of lycopene was able to reduce PSA velocity in this study group.

Aged ; Carotenoids ; therapeutic use ; Dietary Supplements ; Female ; Humans ; Male ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; blood ; drug therapy

The prevalence of prostate cancer, a common malignancy of urinary system in elderly males, has increased rapidly in China in recent years. Currently most prostate cancer patients are treated with androgen deprivation therapy (ADT). However, ADT-induced metabolic disorders such as metabolic syndrome has remarkably impaired the quality of life and decreased the survival rate.
Androgen Antagonists ; adverse effects ; therapeutic use ; Humans ; Male ; Metabolic Diseases ; chemically induced ; Prostatic Neoplasms ; drug therapy ; metabolism

OBJECTIVETo investigate targeted degradation of the androgen receptor (AR) by chimeric molecules (DHT-PROTAC) via the ubiquitin-proteasome pathway in androgen-independent prostate cancer CA-2B cells, and explore the proliferation, secretion and apoptosis of the treated cells.

METHODSC4-2B cells were treated with DHT-PROTAC, and then the expressions of the AR protein and caspase3 in the C4-2B cells were detected by immunohistochemistry and Western blot. The concentration of PSA in the supernatant was examined by ELISA. The cells were counted and their proliferation analyzed by a growth curve. The inhibitory effect on the growth of C4-2B cells was evaluated by MIT assay.

RESULTSCompared with the control group, the DHT-PROTAC-treated group showed an obviously decreased expression of AR proteins with a significant attenuation of the band signals (P < 0.05), a 40% reduction of the AR-positive cells and a 60% decrease of the PSA concentration in the supernatant (P < 0.05). DHT-PROTAC exhibited an inhibitory effect on the C4-2B cells in a time-dependant manner (P < 0.05).

CONCLUSIONThe chimeric molecule (DHT-PROTAC) can target the degradation of androgen receptors, reduce the secretion of PSA and repress the in vitro growth of C4-2B cells.

Antineoplastic Agents ; pharmacology ; Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; Humans ; Male ; Prostate-Specific Antigen ; metabolism ; Prostatic Neoplasms ; drug therapy ; metabolism ; pathology ; Receptors, Androgen ; metabolism

Most prostate cancers initially respond to androgen deprivation therapy (ADT). With the long-term application of ADT, localized prostate cancer will progress to castration-resistant prostate cancer (CRPC), metastatic CRPC (mCRPC), and neuroendocrine prostate cancer (NEPC), and the transcriptional network shifted. Forkhead box protein A1 (FOXA1) may play a key role in this process through multiple mechanisms. To better understand the role of FOXA1 in prostate cancer, we review the interplay among FOXA1-targeted genes, modulators of FOXA1, and FOXA1 with a particular emphasis on androgen receptor (AR) function. Furthermore, we discuss the distinct role of FOXA1 mutations in prostate cancer and clinical significance of FOXA1. We summarize possible regulation pathways of FOXA1 in different stages of prostate cancer. We focus on links between FOXA1 and AR, which may play different roles in various types of prostate cancer. Finally, we discuss FOXA1 mutation and its clinical significance in prostate cancer. FOXA1 regulates the development of prostate cancer through various pathways, and it could be a biomarker for mCRPC and NEPC. Future efforts need to focus on mechanisms underlying mutation of FOXA1 in advanced prostate cancer. We believe that FOXA1 would be a prognostic marker and therapeutic target in prostate cancer.
Humans ; Male ; Androgen Antagonists/therapeutic use* ; Androgens/metabolism* ; Hepatocyte Nuclear Factor 3-alpha/metabolism* ; Mutation ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Receptors, Androgen/metabolism*

Glycogen synthase kinase3 (GSK3α and GSK3β) are serine/threonine protein kinases acting on numerous substrates and involved in the regulation of various cellular functions such as their proliferation, survival, glycogen metabolism, and autophagy. Accumulating evidence indicates that the expression of GSK3α is increased mainly in androgendependent while that of GSK3β in androgenindependent prostate cancer, and that GSK3β is also involved in the regulation of the transactivation of the androgen receptor (AR) and growth of prostate cancer. Animal experiments have proved that some GSK3 inhibitors, such as lithium, can significantly suppress tumor growth in different animal models of prostate cancer. The GSK3 inhibitor is promising to be an important agent for the clinical management of prostate cancer.
Androgens ; Animals ; Cell Line, Tumor ; Glycogen Synthase Kinase 3 ; antagonists & inhibitors ; metabolism ; Glycogen Synthase Kinase 3 beta ; antagonists & inhibitors ; metabolism ; Humans ; Male ; Neoplasm Proteins ; metabolism ; Neoplasms, Hormone-Dependent ; enzymology ; metabolism ; Prostatic Neoplasms ; drug therapy ; enzymology ; pathology ; Receptors, Androgen ; metabolism