scholarly journals In Vitro Assessment of Efficacy and Cytotoxicity of Prunus africana Extracts on Prostate Cancer C4-2 Cells

2021 ◽  
Author(s):  
Peace C. Asuzu ◽  
Alberta N.A. Aryee ◽  
Nicholas Trompeter ◽  
Yasmin Mann ◽  
Samuel A. Besong ◽  
...  

AbstractPhenolic compounds are products of secondary plant metabolism known for their biological activity including their antimicrobial, antioxidant, analgesic, stimulant, anti- carcinogenic, and aphrodisiac properties. The main objective of this study was to assess the potency/cytotoxic effects of Prunus africana extracts on prostate cancer cells in vitro. Using different concentrations of P. africana extracts, prostate cancer C4-2 cells, a hormonally insensitive subline of LNCaP cells, were treated in a proliferation assay. A concentration dependent inhibition of cell growth in cells treated with P. africana bark and root extracts was present from days 1 through 3 of incubation, with the methanol extract of the bark showing the strongest effect. Compared to other plant parts, leaf extracts were significantly less cytotoxic at the same concentrations. As C4-2 cells are hormonally insensitive and designed to mimic advanced prostate cancer, crude extracts of P. africana are a possible treatment option, not only for hormone sensitive prostate cancer, but also advanced, hormonally insensitive prostate cancer.

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Emmanuel Mouafo Tekwu ◽  
Kwabena Mante Bosompem ◽  
William Kofi Anyan ◽  
Regina Appiah-Opong ◽  
Kofi Baffour-Awuah Owusu ◽  
...  

Schistosomiasis is a Neglected Tropical Diseases which can be prevented with mass deworming chemotherapy. The reliance on a single drug, praziquantel, is a motivation for the search of novel antischistosomal compounds. This study investigated the anthelmintic activity of the stem bark and roots ofRauwolfia vomitoriaagainst two life stages ofSchistosoma mansoni. Both plant parts were found to be active against cercariae and adult worms. Within 2 h of exposure all cercariae were killed at a concentration range of 62.5–1000 µg/mL and 250–1000 µg/mL ofR. vomitoriastem bark and roots, respectively. The LC50values determined for the stem bark after 1 and 2 h of exposure were 207.4 and 61.18 µg/mL, respectively. All adult worms exposed to the concentrations range of 250–1000 µg/mL for both plant parts died within 120 h of incubation. The cytotoxic effects against HepG2 and Chang liver cell assessed using MTT assay method indicated that both plant extracts which were inhibitory to the proliferation of cell lines with IC50> 20 μg/mL appear to be safe. This report provides the first evidence of in vitro schistosomicidal potency ofR. vomitoriawith the stem bark being moderately, but relatively, more active and selective against schistosome parasites. This suggests the presence of promising medicinal constituent(s).


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 250-250
Author(s):  
Goutam Chakraborty ◽  
Rahim Hirani ◽  
Subhiksha Nandakumar ◽  
Teja Muralidhar Kalidindi ◽  
Deborah Fidele ◽  
...  

250 Background: Prostate cancer (PC) is a major health problem for men in the U.S. and is the second most common cause of cancer-related deaths in males. Although most PCs are initially sensitive to androgen-deprivation therapy (ADT), the duration of response is variable, and eventually, the cancer becomes resistant to ADT and progresses to metastatic castration-resistant prostate cancer (mCRPC). For mCRPC patients, many initially respond to second-line ARIs (eg. enzalutamide and abiraterone) or docetaxel-based chemotherapy however durable responses are rare. Therefore, it is vital to investigate additional therapeutic strategies to delay or prevent the transition of castration-sensitive prostate cancer (CSPC) to mCRPC. Methods: We treated castration-sensitive human PC cells with various anti-androgen inhibitors to investigate the direct association between Bcl2 expression and AR-pathway. We used a lentiviral-based over-expression method to develop BCL2 over-expressed experimental PC cell line systems and subjected them to various in -vitro and in vivo studies. We studied the combinational effect of Bcl2 and AR inhibitor on the in vitro growth of hormone-sensitive human PC cells and in vivo mice model. Results: We observed that treatment with androgen inhibits but ARIs (eg enzalutamide, apalutamide) restore Bcl2 expression in human CSPC cell lines indicating there is possible direct negative-regulation of the Bcl2 by the AR-signaling pathway. BCL2 over-expressed LNCaP cells show deregulation of the AR pathway, induces PSMA expression, and exhibit relative resistance to enzalutamide indicating that over-expression of BCL2 induces castration resistance in hormone-sensitive PC cells. Our cell growth inhibition assay showed an overall strong additive effect on growth inhibition with enzalutamide and the pharmacological Bcl2 inhibitor (venetoclax) combination on LNCaP cells and 22Rv1 cells. We also observed a negative association between BCL2 and AR pathway in clinical PC cohorts (Localized and mCRPC). In the isograft mice model, we showed the combination of enzalutamide and venetoclax significantly reduces subcutaneous prostate tumor growth and increases overall survival (~2 weeks) compare to control groups of mice. Moreover, using Isogenic cell lines (control and BCL2 over-expressed LNCaP) we showed higher uptake of [68Ga]-PSMA-11 in BCL2 over-expressed prostate tumors compared to control tumors in immunodeficient mice indicating that BCL2 over-expressed PC can monitor non-invasively by PSMA-PET imaging. Conclusions: Our current study develops a rationale for combining ADT with Bcl2-inhibitors for CSPC. We believe this combinatorial therapeutic approach will show great potential for future clinical trials of high-risk hormone-sensitive PC patients and may block the ADT-induced shift of CSPC to mCRPC.


2021 ◽  
Vol 8 (02) ◽  
pp. e62-e68
Author(s):  
Jeeta Sarkar ◽  
Nirmalya Banerjee

AbstractSteroid alkaloid solasodine is a nitrogen analogue of diosgenin and has great importance in the production of steroidal medicines. Solanum erianthum D. Don (Solanaceae) is a good source of solasodine. The aim of this study was to evaluate the effect of different cytokinins on the production of secondary metabolites, especially solasodine in the in vitro culture of S. erianthum. For solasodine estimation, field-grown plant parts and in vitro tissues were extracted thrice and subjected to high-performance liquid Chromatography. Quantitative analysis of different secondary metabolites showed that the amount was higher in the in vitro regenerated plantlets compared to callus and field-grown plants. The present study critically evaluates the effect of the type of cytokinin used in the culture medium on solasodine accumulation in regenerated plants. The highest solasodine content (46.78±3.23 mg g-1) was recorded in leaf extracts of the in vitro grown plantlets in the presence of 6-γ,γ-dimethylallylamino purine in the culture medium and the content was 3.8-fold higher compared to the mother plant.


2018 ◽  
Vol 34 (5) ◽  
pp. 659-667 ◽  
Author(s):  
Abel Joël Yaya Gbaweng ◽  
Hadidjatou Daïrou ◽  
Stephane Zingué ◽  
Talla Emmanuel ◽  
Alembert Tiabou Tchinda ◽  
...  

Planta Medica ◽  
2018 ◽  
Vol 85 (02) ◽  
pp. 118-125 ◽  
Author(s):  
Iwona Stanisławska ◽  
Sebastian Granica ◽  
Jakub Piwowarski ◽  
Joanna Szawkało ◽  
Krzysztof Wiązecki ◽  
...  

AbstractThe gut microbiota-derived metabolites of ellagitannins and green tea catechins, urolithin A (uroA) and 5-(3′,4′,5′-trihydroxyphenyl)-γ-valerolactone (M4), respectively, are among the main compounds absorbed into human system after ingestion of these polyphenols. The aim of this study was to establish the effects of M4, uroA, and their combinations on LNCaP cells, an androgen dependent prostate cancer in vitro model.. The LNCaP cells were incubated with increasing concentrations of tested metabolites. The cell proliferation was determined by measurement of DNA-bisbenzimide H 33 258 complexes fluorescence. The isobolographic analysis was used to establish the type of interaction between metabolites. The apoptosis, androgen receptor (AR) localization, and phosphorylation of Akt kinase were measured by flow cytometry. Prostate-specific antigen (PSA) secretion was determined by ELISA. M4 showed modest antiproliferative activity in LNCaP cells (IC50 = 117 µM; CI: 81 – 154). UroA decreased proliferation (IC50 = 32.7 µM; CI: 24.3 – 41.1) and induced apoptosis of LNCaP cells. The mixture of M4 with uroA had synergistic antiproliferative effect. Moreover, M4 potentiated inhibition of PSA secretion and enhanced retention of AR in cytoplasm caused by uroA. Interestingly, uroA increased levels of pSer473 Akt in LNCaP cells. These results show that colonic metabolites may contribute to chemoprevention of prostate cancer by varied polyphenol-rich diet or composite polyphenol preparations.


2016 ◽  
Vol 15 (4) ◽  
Author(s):  
L.A. Cunha ◽  
T.C. Mota ◽  
P.C.S. Cardoso ◽  
D.D.F.A. Alcântara ◽  
R.M.R. Burbano ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Richard Komakech ◽  
Youngmin Kang ◽  
Jun-Hwan Lee ◽  
Francis Omujal

Prostate cancer remains one of the major causes of death worldwide. In view of the limited treatment options for patients with prostate cancer, preventive and treatment approaches based on natural compounds can play an integral role in tackling this disease. Recent evidence supports the beneficial effects of plant-derived phytochemicals as chemopreventive and chemotherapeutic agents for various cancers, including prostate cancer. Prunus africana has been used for generations in African traditional medicine to treat prostate cancer. This review examined the potential roles of the phytochemicals from P. africana, an endangered, sub-Saharan Africa plant in the chemoprevention and chemotherapy of prostate cancer. In vitro and in vivo studies have provided strong pharmacological evidence for antiprostate cancer activities of P. africana-derived phytochemicals. Through synergistic interactions between different effective phytochemicals, P. africana extracts have been shown to exhibit very strong antiandrogenic and antiangiogenic activities and have the ability to kill tumor cells via apoptotic pathways, prevent the proliferation of prostate cancer cells, and alter the signaling pathways required for the maintenance of prostate cancer cells. However, further preclinical and clinical studies ought to be done to advance and eventually use these promising phytochemicals for the prevention and chemotherapy of human prostate cancer.


2005 ◽  
Vol 16 (4) ◽  
pp. 417-422 ◽  
Author(s):  
Aur??lie Cabrespine ◽  
Jacques-Olivier Bay ◽  
Chantal Barthomeuf ◽  
Herv?? Cur?? ◽  
Philippe Chollet ◽  
...  

2020 ◽  
Author(s):  
Yongheng Ye ◽  
Lingli Zhang ◽  
Yuhu Dai ◽  
Zhi Wang ◽  
Cuie Li ◽  
...  

Abstract Treatment of bone metastasis of prostate cancer remains a formidable challenge. The skeleton has a poorer blood supply, leading to inadequate drug distribution into the bone after administration. This study aimed to develop aptamer-anchored hyperbranched poly (amido amine) (HPAA) for the systemic delivery of miRNA-133a-3p and to evaluate its therapeutic potential against bone metastasis of prostate cancer in vivo and in vitro. A glutathione (GSH)-responsive cationic HPAA was prepared by the Michael addition reaction. Furthermore, HPAA-PEG was produced by PEGylation, and then the aptamer targeted to prostate-specific membrane antigen (PSMA) was conjugated to the HPAA-PEG. The obtained HPAA-PEG-APT could form nanocomplexes with miRNA-133a-3p through electrostatic adsorption. The results of immunocytochemistry indicated that the complexes could target PSMA-expressing LNCaP cells. The ability of HPAA-PEG-APT to facilitate the delivery of miRNA-133a-3p into LNCaP cells was proven, and HPAA-PEG-APT/miRNA-133a-3p demonstrated enhanced antitumor activity, lower cytotoxicity and better biocompatibility in vitro. Moreover, in a mouse tibial injection tumor model, the intravenous injection of the HPAA-PEG-APT/miRNA-133a-3p complex significantly inhibited cancer growth and extended the survival time. In summary, this study provided an aptamer-anchored HPAA-loaded gene system to deliver miRNA-133a-3p for better therapeutic efficacy of bone metastasis of prostate cancer.


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