Green tea catechins and intracellular calcium dynamics in prostate cancer cells

• Main Author: Carla Marchetti
• Format: Article
• Language: English
• Published: AIMS Press 2021-01-01
• Series: AIMS Molecular Science
• Subjects: androgen-resistant prostate cancer pc3 cells; du145 cells; green tea extract; internal ca2+ release
• Online Access: http://www.aimspress.com/article/doi/10.3934/molsci.2021001?viewType=HTML

Perturbations of internal Ca²⁺ ([Ca²⁺]_i) homeostasis play a key role in several pathologies and in neoplastic transformation, where deregulated cell proliferation, together with the suppression of apoptosis, provides the condition for abnormal tissue growth and invasion. Green tea catechins have been shown to affect cancer development by interference with basic cellular functions, most of which are mediated by [Ca²⁺]_i. Prostate cancer (PCa) is one of the most common malignancy in men in Western countries and the androgen-independent carcinoma is a lethal form for which there is still no effective therapy. Different evidences suggested that consumption of green tea may have beneficial effects against PCa. We have previously described how the main green tea flavonoid, (−)-epigallocatechin-3-gallate (EGCG), inhibited proliferation and induced dose-dependent peaks of [Ca²⁺]_i in metastatic androgen-insensitive DU145 and PC3 PCa cells, by a mechanism that combined Ca²⁺ entry and Ca²⁺-induced Ca²⁺ release. In the present study, we studied the effect of green tea extract (GTE) on the same cell lines. Proliferation, measured by MTT assay, was inhibited by GTE with IC₅₀ close to 60 µg/ml, a value that is higher than that expected by EGCG effect alone. [Ca²⁺]_i, measured in real time by the fluorescent dye Fura-2, was transiently increased by GTE by a mechanism that resembled that described for EGCG, but was largely independent of external Ca²⁺. These observations suggested that other components, acting in synergy with EGCG, were involved in GTE effect, and confirmed the view that the alleged health benefits of green tea for PCa prevention may be related to [Ca²⁺]_i deregulation in malignant cells. These results may be significant to understand the functional mechanisms by which flavonoids exert their beneficial or toxic actions.