L-securinine inhibits cell growth and metastasis of human androgen-independent prostate cancer DU145 cells via regulating mitochondrial and AGTR1/MEK/ERK/STAT3/PAX2 apoptotic pathways

Abstract The present study aims to evaluate the anticancer effect of L-securinine on androgen-independent prostate cancer (AIPC) DU145 cells. L-securinine (2.5, 5, and 10 μM) treatment for 24, 48 and 72 h displayed strong growth inhibitory effect on DU145 cells in a concentration and time-dependent fashion but has less toxicity toward normal androgen-dependent LNCaP cells. Hoechst 332582 staining of DU145 cells and Annexin V-FITC/ PI dual-labeling followed by flow cytometry assay identified that this growth inhibition by L-securinine would be due to the induction of apoptosis. Moreover Transwell assay revealed that L-securinine significantly inhibited the cell migration/invasion ability of DU145 cells. Furthermore, results of western blotting showed that the involvement of mitochondrial apoptotic pathway in the L-securinine-induced apoptosis of DU145 cell, as evidenced by an increase in the protein expression of Bax, cleaved caspase-9, cleaved caspase-3, cytosolic cytochrome c, and cleaved PARP, together with a unchanged cleaved caspase-8 and decreased Bcl-2 protein expression. Also, L-securinine-induced antimetastatic activity in DU145 cells was associated with decreased protein expression of MMP-2 and MMP-9 and concurrent reduction of VEGF. In addition, further studies revealed that L-securinine may inhibit the protein expression of AGTR1, p-MEK1/2, p-ERK1/2, p-STAT3, PAX2, and p-PAX2, while the expression of ERK1/2, MEK1/2, and STAT3 protein retains intact. These findings suggest that L-securinine may be a promising chemopreventive agent against AIPC.

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tRNALys-Derived Fragment Alleviates Cisplatin-Induced Apoptosis in Prostate Cancer Cells

Pharmaceutics ◽

10.3390/pharmaceutics13010055 ◽

2021 ◽

Vol 13 (1) ◽

pp. 55

Author(s):

Changwon Yang ◽

Minkyeong Lee ◽

Gwonhwa Song ◽

Whasun Lim

Keyword(s):

Prostate Cancer ◽

Cancer Cells ◽

Suppressor Gene ◽

Prostate Cancer Cells ◽

Apoptotic Pathway ◽

Normal Prostate ◽

Prostate Cells ◽

Du145 Cells ◽

Induced Apoptosis ◽

Related Proteins

Cisplatin is a standard treatment for prostate cancer, which is the third leading cause of cancer-related deaths among men globally. However, patients who have undergone cisplatin can rxperience relapse. tRNA-derived fragments (tRFs) are small non-coding RNAs generated via tRNA cleavage; their physiological activities are linked to the development of human diseases. Specific tRFs, including tRF-315 derived from tRNALys, are highly expressed in prostate cancer patients. However, whether tRF-315 regulates prostate cancer cell proliferation or apoptosis is unclear. Herein, we confirmed that tRF-315 expression was higher in prostate cancer cells (LNCaP, DU145, and PC3) than in normal prostate cells. tRF-315 prevented cisplatin-induced apoptosis and alleviated cisplatin-induced mitochondrial dysfunction in LNCaP and DU145 cells. Moreover, transfection of tRF-315 inhibitor increased the expression of apoptotic pathway-related proteins in LNCaP and DU145 cells. Furthermore, tRF-315 targeted the tumor suppressor gene GADD45A, thus regulating the cell cycle, which was altered by cisplatin in LNCaP and DU145 cells. Thus, tRF-315 protects prostate cancer cells from mitochondrion-dependent apoptosis induced by cisplatin treatment.

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Poly-L-arginine: Enhancing Cytotoxicity and Cellular Uptake of Doxorubicin and Necrotic Cell Death

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520618666180412114750 ◽

2019 ◽

Vol 18 (10) ◽

pp. 1448-1456 ◽

Cited By ~ 3

Author(s):

Bahareh Movafegh ◽

Razieh Jalal ◽

Zobeideh Mohammadi ◽

Seyyede A. Aldaghi

Keyword(s):

Cell Death ◽

Cellular Uptake ◽

Combined Treatment ◽

Annexin V ◽

Cell Penetrating Peptides ◽

Short Exposure ◽

Dependent Manner ◽

Du145 Cells ◽

Induced Apoptosis ◽

Resistance To Doxorubicin

Objective: Cell resistance to doxorubicin and its toxicity to healthy tissue reduce its efficiency. The use of cell-penetrating peptides as drug delivery system along with doxorubicin is a strategy to reduce its side effects. In this study, the influence of poly-L-arginine on doxorubicin cytotoxicity, its cellular uptake and doxorubicin-induced apoptosis on human prostate cancer DU145 cells are assessed. Methods: The cytotoxicity of doxorubicin and poly-L-arginine, alone and in combination, in DU145 cells was evaluated at different exposure times using MTT assay. The influence of poly-L-arginine on doxorubicin delivery into cells was evaluated by fluorescence microscopy and ultraviolet spectroscopy. DAPI and ethidium bromide- acridine orange stainings, flow cytometry using annexin V/propidium iodide, western blot analysis with anti-p21 antibody and caspase-3 activity were used to examine the influence of poly-L-arginine on doxorubicininduced cell death. Results: Poly-L-arginine had no cytotoxicity at low concentrations and short exposure times. Poly-L-arginine increased the cytotoxic effect of doxorubicin in DU145 cells in a time-dependent manner. But no significant reduction was found in HFF cell viability. Poly-L-arginine seems to facilitate doxorubicin uptake and increase its intracellular concentration. 24h combined treatment of cells with doxorubicin (0.5 µM) and poly-L-arginine (1 µg ml-1) caused a small increase in doxorubicin-induced apoptosis and significantly elevated necrosis in DU145 cells as compared to each agent alone. Conclusion: Our results indicate that poly-L-arginine at lowest and highest concentrations act as proliferationinducing and antiproliferative agents, respectively. Between these concentrations, poly-L-arginine increases the cellular uptake of doxorubicin and its cytotoxicity through induction of necrosis.

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Myeloid cell leukemia-1 is a key molecular target for mithramycin A-induced apoptosis in androgen-independent prostate cancer cells and a tumor xenograft animal model

Cancer Letters ◽

10.1016/j.canlet.2012.09.009 ◽

2013 ◽

Vol 328 (1) ◽

pp. 65-72 ◽

Cited By ~ 25

Author(s):

Eun-Sun Choi ◽

Ji-Youn Jung ◽

Jin-Seok Lee ◽

Jong-Hwan Park ◽

Nam-Pyo Cho ◽

...

Keyword(s):

Prostate Cancer ◽

Animal Model ◽

Myeloid Cell ◽

Molecular Target ◽

Tumor Xenograft ◽

Cell Leukemia ◽

Prostate Cancer Cells ◽

Mithramycin A ◽

Induced Apoptosis ◽

Androgen Independent

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Induction of cell death in prostate cancer cells by escopoletin, a promising treatment strategy

Bangladesh Journal of Pharmacology ◽

10.3329/bjp.v10i3.23095 ◽

2015 ◽

Vol 10 (3) ◽

pp. 500 ◽

Cited By ~ 1

Author(s):

Da Chen ◽

Xiao-Yi Zhang ◽

Fa-Zhu Zheng ◽

Hai-Tao Wang ◽

Jian-Liang Cai ◽

...

Keyword(s):

Prostate Cancer ◽

Cell Death ◽

Antioxidant Activities ◽

Apoptotic Cell ◽

Annexin V ◽

Cycle Arrest ◽

Anti Cancer ◽

Enhanced Expression ◽

Promising Treatment ◽

Du145 Cells

<p>Escopoletin, a phenolic compound belonging to anthocyanin family shows promising antioxidant activities. In the present study, anti-cancer effects of escopoletin treatment in DU145 cells were investigated. The sulphorhodamine-B staining and annexin V and propidium iodide were respectively used for the analysis of cell viability and death. The results revealed a significantly higher cytotoxicity by escopoletin that caused cell death in DU145 cells. Escopoletin treatment in DU145 cells markedly inhibited cell growth through non-apoptotic cell death and induced significant reactive oxygen species (ROS) production. It also induced G1 cell cycle arrest and cyclin D1 accumulation through the enhanced expression of p21. However, the effect of escopoletin on DU145 cells was reversed by pretreatment with glutathione antioxidant. This suggests that escopoletin induced generation of ROS is responsible for the increased cytotoxicity in DU145 cells. Thus, escopoletin exhibits potential therapeutic efficacy for the treatment of prostate cancer.</p><p> </p>

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Vulpinic Acid as a Natural Compound Inhibits the Proliferation of Metastatic Prostate Cancer Cell by Inducing Apoptosis

10.21203/rs.3.rs-515712/v1 ◽

2021 ◽

Author(s):

Demet Cansaran Duman ◽

Gamze Guney Eskiler ◽

Betül Çolak ◽

Elif Sozen Kucukkara

Keyword(s):

Prostate Cancer ◽

Metastatic Prostate Cancer ◽

Molecular Mechanisms ◽

Treatment Options ◽

Annexin V ◽

Current Treatment ◽

Pcr Analysis ◽

G1 Arrest ◽

Advanced Analysis ◽

Induced Apoptosis

Abstract Lichen secondary metabolites have drawn considerable attention in recent years due to limitations of current treatment options. Vulpinic acid (VA) obtained from Letharia vulpina lichen species exerts a remarkable cytotoxic effect on different cancer types. However, the therapeutic efficacy of VA in metastatic prostate cancer (mPC) cells has not been investigated. In the present study, we aimed to identify VA-mediated cytotoxicity in PC-3 mPC cells compared with control cells. After identification of the cytotoxic concentrations of VA, VA induced apoptosis was analyzed by Annexin V, cell cycle, acridine orange and propidium iodide staining and RT-PCR analysis. Our findings showed that VA significantly decreased the viability of PC-3 cells (p < 0.01) and caused a considerable early apoptotic effect through G0/G1 arrest, nuclear bleebing and the activation of particularly initiator caspases. Therefore, VA may be a potential treatment option for mPC patients. However, the underlying molecular mechanisms of VA-induced apoptosis with advanced analysis should be further performed.

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The Study of Anticancer Activity of Satureja Khuzestanica Alcoholic Extracts On Expression of Bcl2 And Bax Genes In The Pc3 Cell Line

10.21203/rs.3.rs-296598/v1 ◽

2021 ◽

Author(s):

Saman Kazemi ◽

asghar tanomand ◽

Hossein Soltanzadeh ◽

Gholamreza Shahsavari

Keyword(s):

Gene Expression ◽

Prostate Cancer ◽

Cancer Cells ◽

Rna Extraction ◽

Inhibitory Effect ◽

Chloroform Extract ◽

Antioxidant Compounds ◽

Anticancer Properties ◽

Satureja Khuzestanica ◽

Induced Apoptosis

Abstract Introduction: Prostate cancer is the most common cancer among men after lung cancer. It has grown in Iran in recent years. The use of medicinal plants is one of the most useful ways that causes the least side effects. Due to high levels of antioxidant compounds, Satureja khuzestanica is a good source for drug use to treat and prevent the development and progress of cancers. The aim of the present study was to evaluate the anti-cancer property of Satureja khuzestanica extract on the expression of Bcl2 and Bax genes in prostate cancer cell lines.Methodology: After collecting the plant in spring, the chloroform extract was prepared by rotary device. PC3 cancer cells were incubated at different concentrations of the extract for 24 hours. The inhibitory effect of the extract was evaluated using MTT assay as IC50. To evaluate apoptosis, the level of expression of Bax and BCL-2 genes after RNA extraction and transformation to cDNA were evaluated using Real Time PCR. All data were analyzed using REST software.Results: The results revealed a direct and significant relationship between the two variables of drug composition and rate of PC3 cell death. This composition increased Bax gene expression and decreased BCL-2 gene expression and induced apoptosis (P <0.05).Discussion and Conclusion: Based on the results, Satureja khuzestanica extract is likely to have anticancer properties and seems to be a new drug for killing prostate cancer cells.

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Dehydroepiandrosterone Administration or Gαq Overexpression Induces β-Catenin/T-Cell Factor Signaling and Growth via Increasing Association of Estrogen Receptor-β/Dishevelled2 in Androgen-Independent Prostate Cancer Cells

Endocrinology ◽

10.1210/en.2009-0885 ◽

2010 ◽

Vol 151 (4) ◽

pp. 1428-1440 ◽

Cited By ~ 11

Author(s):

Xunxian Liu ◽

Julia T. Arnold ◽

Marc R. Blackman

Keyword(s):

Prostate Cancer ◽

Estrogen Receptor ◽

T Cell ◽

Cell Growth ◽

Protein Expression ◽

Cyclin D1 ◽

D1 Protein ◽

Nutritional Supplement ◽

T Cell Factor ◽

Androgen Independent

β-Catenin/T-cell factor signaling (β-CTS) plays multiple critical roles in carcinogenesis and is blocked by androgens in androgen receptor (AR)-responsive prostate cancer (PrCa) cells, primarily via AR sequestration of β-catenin from T-cell factor. Dehydroepiandrosterone (DHEA), often used as an over-the-counter nutritional supplement, is metabolized to androgens and estrogens in humans. The efficacy and safety of unregulated use of DHEA are unclear. We now report that DHEA induces β-CTS via increasing association of estrogen receptor (ER)-β with Dishevelled2 (Dvl2) in AR nonresponsive human PrCa DU145 cells, a line of androgen-independent PrCa (AiPC) cells. The induction is temporal, as assessed by measuring kinetics of the association of ERβ/Dvl2, protein expression of the β-CTS targeted genes, c-Myc and cyclin D1, and cell growth. However, in PC-3 cells, another human AiPC cell line, DHEA exerts no detectible effects, partly due to their lower expression of Gα-subunits and DHEA down-regulation of ERβ/Dvl2 association. When Gαq is overexpressed in PC-3 cells, β-CTS is constitutively induced, including increasing c-Myc and cyclin D1 protein expression. This effect involved increasing associations of Gαq/Dvl2 and ERβ/Dvl2 and promoted cell growth. These activities require ERβ in DU-145 and PC-3 cells because they are blocked by ICI 182–780 treatment inactivating ERβ, small interfering RNA administration depleting ERβ, or AR overexpression arresting ERβ. These data suggest that novel pathways activating β-CTS play roles in the progression of AiPC. Although DHEA may enhance PrCa cell growth via androgenic or estrogenic pathways, the effects of DHEA administration on clinical prostate function remain to be determined.

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Abstract 1324: PMEPA1 enhances the prostate cancer cell growth inhibitory effect of MDV3100 and bicalutamide.

10.1158/1538-7445.am2013-1324 ◽

2013 ◽

Author(s):

Hua E. Li ◽

Daniel Heidenberg ◽

Albert Dobi ◽

Shiv Srivastava

Keyword(s):

Prostate Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Inhibitory Effect ◽

Growth Inhibitory Effect ◽

Cancer Cell Growth ◽

Growth Inhibitory

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Inhibition of LOXL2 Enhances the Radiosensitivity of Castration-Resistant Prostate Cancer Cells Associated with the Reversal of the EMT Process

BioMed Research International ◽

10.1155/2019/4012590 ◽

2019 ◽

Vol 2019 ◽

pp. 1-10 ◽

Cited By ~ 7

Author(s):

Peng Xie ◽

Hongliang Yu ◽

Feijiang Wang ◽

Feng Yan ◽

Xia He

Keyword(s):

Prostate Cancer ◽

Cell Apoptosis ◽

Castration Resistant Prostate Cancer ◽

Prostate Cancer Cells ◽

Castration Resistant ◽

Du145 Cells ◽

Androgen Independent

Introduction. Radiotherapy is the mainstay in the treatment of prostate cancer. However, significant radioresistance of castration-resistant prostate cancer (CRPC) cells constitutes a main obstacle in the treatment of this disease. By using bioinformatic data mining methods, LOXL2 was found to be upregulated in both androgen-independent prostate cancer cell lines and radioresistant tumor samples collected from patients with prostate cancer. We speculate that LOXL2 may play an important role in the radioresistance of CRPC cells. Methods. The effect of LOXL2 knockdown on the radiosensitivity of androgen-independent prostate cancer cells lines was measured by the clonogenic assay and xenograft tumor experiments under in vitro and in vivo conditions, respectively. In studies on the mechanism, we focused on the EMT phenotype changes and cell apoptosis changes induced by LOXL2 knockdown in DU145 cells. The protein levels of three EMT biomarkers, namely, E-cadherin, vimentin, and N-cadherin, were measured by western blotting and immunohistochemical staining. Cell apoptosis after irradiation was measured by flow cytometry and caspase-3 activity assay. Salvage experiment was also conducted to confirm the possible role of EMT in the radiosensitization effect of LOXL2 knockdown in CRPC cells. Results. LOXL2 knockdown in CRPC cells enhanced cellular radiosensitivity under both in vitro and in vivo conditions. A significant reversal of EMT was observed in LOXL2-silenced DU145 cells. Cell apoptosis after irradiation was significantly enhanced by LOXL2 knockdown in DU145 cells. Results from the salvage experiment confirmed the key role of EMT process reversal in the radiosensitization effect of LOXL2 knockdown in DU145 cells. Conclusions. LOXL2 plays an important role in the development of cellular radioresistance in CRPC cells. Targeting LOXL2 may be a rational avenue to overcome radioresistance in CRPC cells. A LOXL2-targeting strategy for CRPC treatment warrants detailed investigation in the future.

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