.jpg)
Scientific studies on theaflavins
TFs have extensively been studied for their anticancer affects both in vitro and in vivo cancer models. Ovarian cancer caused the highest mortalities in the cancerous gynecologic issues, and TF3 has effective role to diminish this. TF3 stimulates programmed cell death via an apoptotic pathway in the ovarian carcinoma-derived OVCAR-3 cell line [16]. TF3 increases the rate of apoptosis in rate-3 cells following a dose-dependent manner by significantly enhancing the expression of cleaved poly (ADP-ribose) polymerase 1 (PARP-1) and triggered various caspases, viz., casp-3, casp-7, casp-8, and casp-9 [16]. The casp-8 triggers downstream effector caspases responsible for the cleavage of their respective proteins, such as PARP-1. The initiation of the PARP-1 cleavage is mainly done by the caspases that initiates apoptosis by the intervention of TF3 [16, 17]. In an in vitro study, various concentrations of TF3 showed a strong but targeted effect on the growth and proliferation of human oral squamous carcinoma (HSC-2 cell line); however, no effect was seen on the normal GN46 fibroblast cells [18]. Moreover, HSC-2 cells were forced to apoptose by TF3-mediated cleavage of the PARP-1, leading to the increased expression of casp-3 levels. While, in GN46 fibroblast cells, no any alteration in the protein expression of casp-3 was seen [18]. Thus, TF3 depicted little or no harm to normal ovarian cells but combined with cisplatin, and it possesses a multifold strong antiproliferation effect against A2780/CP70 and OVCAR3 ovarian cancer cells [19]. The underlying mechanism for this combined anticancer effect of TF3 + cisplatin is the increased accumulation of platinum, and its adduct complex with DNA (Pt-DNA), which may increase DNA damage, reduced the glutathione expression with the increased expression of copper transporter 1 (CTR1) protein in the cancer cell lines [19]. Herein, TF3 may facilitate the initiation of cisplatin-induced inhibitory effects in cancer cells. The ovarian cancer stem cells (CSCs) facilitate cancer recurrence and drug resistance to lessen the long-term survival ratio in patients suffering from advanced ovarian cancer [12]. TF3 inhibited the active growth of A2780/CP70 and OVCAR3 tumorsphere cells by decreasing cell viability and colony formation capability while upregulated the protein expression of casp-3 and casp-7 in cancer cells following the Wnt/β-catenin signaling cascade [12].