Epigallocatechin-3-Gallate: The Prospective Targeting of Cancer Stem Cells and Preventing Metastasis of Chemically-Induced Mammary Cancer in Rats

Abstract

Background: Cancer stem cells are a subpopulation of tumor cells that are capable of self-renewal, capable of tumor recurrence and metastasis, and in addition are resistant to current cancer therapies. Epigallocatechin-3-gallate is a type of catechin found in green tea that is known for its powerful chemoprotective ability. Hence, this study aimed to investigate the effect of epigallocatechin-3-gallate on 7, 12 dimethylbenzanthracene-induced tumor metastasis, angiogenesis and cancer stem cells.

Materials and methods: For this purpose, 3 groups of virgin femal rats with 7,12 dimethylbenzanthracene-induced mammary cancer were treated using epigallocatechin-3-gallate, paclitaxel or their combination.

Results: It was found that epigallocatechin-3-gallate exhibited significant chemopreventive effects and anti-cancer stem cell activity through several pathways, including a significant decrease in the size and number of tumors per rat, significant amelioration of the oxidative stress markers' alterations and significant inhibition of CD44, VEGF, Ki-67 and MMP-2 expression associated with a significantly increased expression of caspase-3. Histopathologically, therapy with epigallocatechin-3-gallate resulted in marked necrosis of the neoplastic cells and the tumor masses were mostly replaced by proliferated fibrous tissue so that histological confirmation of a previous tumor was not possible at that site. However, in the combination therapy the neoplastic cells showed marked vacuolation, haphazard arrangement and extensive nuclear pyknosis accompanied with many apoptotic bodies. Therapy with the sole paclitaxel caused variable degrees of necrosis among the neoplastic cells. Additionally, the combination of epigallocatechin-3-gallate and paclitaxel significantly enhanced the later anticancer efficacy.

Conclusions: Epigallocatechin-3-gallatecould be offered as an unprecedented curative strategy to eradicate cancer.

Keywords: Antioxidant; CD44; Cancer stem cells; Epigallocatechin gallate; Ki-67; Mammary tumor.