Antitumor Activities of Green Tea by Up-regulation of miR-181a Expression in LNCaP Cells Using 3D Cell Culture Model

Abstract

Background: Prostate Cancer (PCa) is the major reason for the high mortality rates among men worldwide. In fact, current therapeutic approaches are not successful. It appears that discovering more effective methods considering several parameters such as availability, low cost, and no toxicity to normal cells is one of the biggest challenges for interested researchers. Green tea (extracted from the plant Camellia sinensis) with high level of polyphenolic compounds and as the most globally consumed beverage has attracted considerable interest. MicroRNAs (or miRNAs) were considered as novel tools in cancer therapy which modulate various biological events in cell by regulation of gene expression. The aim of the current study was to evaluate the antitumor activity of green tea in LNCaP cells through up-regulation of miR-181a expression.
 Methods: First, LNCaP cells were cultured and by using quantitative real time PCR (qRT-PCR) and western blot methods, the expression levels of Bax and BCL2 were analyzed. Next, a 3D cell culture model was applied to evaluate the expression of miRNA-181a in LNCaP cells. 
 Results: It was shown that green tea induced cellular apoptosis. The high number of apoptotic nuclei was also shown by using DAPI staining. The inhibition of tumor growth was revealed by analyzing the size and number of spheroids. Also, up-regulation of miR-181a expression in LNCaP cells was revealed after treatment with green tea.
 Conclusion: Our results are helpful to design antitumor regimens based on consumption of green tea through up-regulation of miRNA-181a expression and induction of apoptosis.

Comparative Anticancer Potential of Green Tea Extract and Epigallocatechin-3-gallate on Breast Cancer Spheroids

“…Additionally, changes in the adhesion behavior of treated cells consistent with a reduction in the formation of colonies were also reported [ 41 ]. GTE’s ability to reduce spheroid growth has been demonstrated in 3D cultures of 4T1 murine mammary carcinoma cells [ 42 ] and prostate LNCaP [ 43 ]. We also demonstrated that spheroid formation was impaired in a GTE-containing medium, leading to irregular aggregates.…”

“…The GT mechanisms of action on MMPs can also be seen through the control of their translation, and in this field the modulation of microRNAs may offer a therapeutic alternative. The exposure of LNCaP prostate cancer spheroids to 100–1000 µg/mL of GTE for 48 h led to an increase in miR-181a expression [ 43 ]. MiR-181a are known to inhibit migration and angiogenesis through the regulation of MMP-14 in SK-3 breast cancer cells [ 46 ].…”

Let’s Go 3D! New Generation of Models for Evaluating Drug Response and Resistance in Prostate Cancer

“…Curcumin is one of the most investigated natural compounds in this context, and it has demonstrated anti-tumor effects on many tumor types, including prostate [ 113 , 176 , 177 ]. However, the search for new natural inhibitors continues, as many are being tested on PC spheroids, such as flavokawain A [ 178 ], brachydin A [ 109 ], green tea extract [ 110 ], rosmarinic acid [ 116 ], or grape seed extract [ 115 ].…”

Polyphenon E Effects on Gene Expression in PC-3 Prostate Cancer Cells

“…The major polyphenolic constituent of Poly E, EGCG, has been reported to regulate several key cellular signaling pathways [12][13][14], proinflammatory factors [15,16], and apoptosis [17,18]. It has been suggested that EGCG is less effective alone in its beneficial health properties than it is in conjunction with the other polyphenolic compounds naturally found in green tea, and in Poly E [19].…”