Purified Tea (Camellia sinensis (L.) Kuntze) Flower Saponins Induce the p53-Dependent Intrinsic Apoptosis of Cisplatin-Resistant Ovarian Cancer Cells

Abstract

Ovarian cancer is currently ranked at fifth in cancer deaths among women. Patients who have undergone cisplatin-based chemotherapy can experience adverse effects or become resistant to treatment, which is a major impediment for ovarian cancer treatment. Natural products from plants have drawn great attention in the fight against cancer recently. In this trial, purified tea (Camellia sinensis (L.) Kuntze) flower saponins (PTFSs), whose main components are Chakasaponin I and Chakasaponin IV, inhibited the growth and proliferation of ovarian cancer cell lines A2780/CP70 and OVCAR-3. Flow cytometry, caspase activity and Western blotting analysis suggested that such inhibitory effects of PTFSs on ovarian cancer cells were attributed to the induction of cell apoptosis through the intrinsic pathway rather than extrinsic pathway. The p53 protein was then confirmed to play an important role in PTFS-induced intrinsic apoptosis, and the levels of its downstream proteins such as caspase families, Bcl-2 families, Apaf-1 and PARP were regulated by PTFS treatment. In addition, the upregulation of p53 expression by PTFSs were at least partly induced by DNA damage through the ATM/Chk2 pathway. The results help us to understand the mechanisms underlying the effects of PTFSs on preventing and treating platinum-resistant ovarian cancer.

Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy

“…A few examples of saponins with biological importance include ginsenoside RK1, panax notoginsen, panax quinquefolius, and paris saponin-II [156][157][158]. In addition, saponins collected from flowers, such as Camellia sinensis, appear to sensitize cisplatin-resistant cells by inducing apoptosis in certain ovarian cancers [159,160]. A synergistic effect of saponins, such as β-elemene (Rhizoma zedoariae) and from medicago species, has been observed in cervical and breast cancer when treated in combination with cisplatin [161,162].…”

Pharmacological Approaches to Attenuate Inflammation and Obesity with Natural Products Formulations by Regulating the Associated Promoting Molecular Signaling Pathways

“…Green tea ( C. sinensis ) contains many bioactive compounds, including catechins, caffeine, saponins, theanine, vitamins, mineral oil, and trace elements [ 51 , 52 ]. Green tea components have many biological and biochemical effects, including antimutation [ 53 ], anticarcinogenesis [ 54 ], antioxidation [ 55 ], apoptosis-inducing [ 41 ], and antiangiogenesis effects. Major bioactive compounds present in green tea seeds include flavonoids, EGCG, saponin glycosides, kaempferol, and naringenin [ 56 – 59 ].…”

Co-Chemotherapy Effect of The Extract of Hibiscus Sabdariffa and Cisplatin Against Apoptosis and Anti-Proliferation on T47d and Vero Cells

“…Another study found that saponins can protect against nephrotoxicity induced by cisplatin. Saponins cause cell resistance because cisplatin becomes sensitized by inducing apoptosis in ovarian cancer 36 . The synergistic increase in cytotoxic effect that occurs in the combination of HSE and cisplatin needs to be investigated further.…”