The Antiproliferative Effect of Chakasaponins I and II, Floratheasaponin A, and Epigallocatechin 3-O-Gallate Isolated from Camellia sinensis on Human Digestive Tract Carcinoma Cell Lines

Abstract

Acylated oleanane-type triterpene saponins, namely chakasaponins I (1) and II (2), floratheasaponin A (3), and their analogs, together with catechins—including (–)-epigallocatechin 3-O-gallate (4), flavonoids, and caffeine—have been isolated as characteristic functional constituents from the extracts of “tea flower”, the flower buds of Camellia sinensis (Theaceae), which have common components with that of the leaf part. These isolates exhibited antiproliferative activities against human digestive tract carcinoma HSC-2, HSC-4, MKN-45, and Caco-2 cells. The antiproliferative activities of the saponins (1–3, IC50 = 4.4–14.1, 6.2–18.2, 4.5–17.3, and 19.3–40.6 µM, respectively) were more potent than those of catechins, flavonoids, and caffeine. To characterize the mechanisms of action of principal saponin constituents 1–3, a flow cytometric analysis using annexin-V/7-aminoactinomycin D (7-AAD) double staining in HSC-2 cells was performed. The percentage of apoptotic cells increased in a concentration-dependent manner. DNA fragmentation and caspase-3/7 activation were also detected after 48 h. These results suggested that antiproliferative activities of 1–3 induce apoptotic cell death via activation of caspase-3/7.

Inhibitory Effects of Total Triterpenoid Saponins Isolated from the Seeds of the Tea Plant (Camellia sinensis) on Human Ovarian Cancer Cells

“…For instance, Theasaponin E 1 has been theorized as a possible cancer treatment option because of its anti-angiogenesis mechanisms [ 35 ]. Chakasaponins I and II and floratheasaponin A showed anti-proliferative activities through apoptotic-induced cell death by activation of caspase-3/7 in HSC-2 cells [ 38 ]. Little research has been published on tea saponins beneficial biological activities on ovarian carcinoma.…”

“…TS has been demonstrated as being an excellent bio-surfactant with numerous pharmacological activities. TS has been documented as having gastroprotective [ 33 ], anti-fungal [ 34 ], anti-viral [ 25 ], anti-oxidative [ 24 ], anti-obesity [ 35 ], anti-inflammatory [ 24 , 28 ], anti-hyperglycemic [ 27 ], immunomodulatory [ 36 ], and anti-tumor [ 35 , 37 , 38 ] tendencies. However, unlike other phenolic compounds, EGCG [ 39 , 40 , 41 ] and TFs [ 37 , 42 ] separated from tea plants, TS has not been reported as having pharmacological influences on human ovarian cancer.…”

Standardized Saponin Extract from Baiye No.1 Tea (Camellia sinensis) Flowers Induced S Phase Cell Cycle Arrest and Apoptosis via AKT-MDM2-p53 Signaling Pathway in Ovarian Cancer Cells

“…Kitagawa et al showed that Chakasaponin I, II, and Floratheasaponin A have inhibitory effects on human gastrointestinal cancer cells HSC-2, HSC-4, MKN-45, and Caco-2, and the effect is stronger than catechin, flavonoids, and caffeine. The inhibition of HSC-2 cell proliferation may be due to the induction of cell cycle arrest in the G2/M phase and activation of apoptosis [16]. Previously, we also reported the effects of tea flower saponins containing Chakasaponin II and other 13 monomers on ovarian cancer cells; the results demonstrated that tea flower saponins shows strong anticancer activity by inducing apoptosis and S phase cell cycle arrest in human OVCAR-3 and A2780/CP70 cancer cells [17].…”

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

“…We previously identified 21 triterpenoid saponins in extracts from tea flowers in selected cultivars [23]. In recent years, the bio-functional effects of tea flower saponins such as antihyperlipidemic, antihyperglycemic, anti-obesity, anti-cancer, and gastroprotective effects have been reported [24][25][26], among which Chakasaponin I has been reported to have antihyperlipidemic and antihyperglycemic [27], anti-cancer [26], and anti-obesity [28] effects. We previously reported that tea flower saponins containing 14 triterpenoid saponins could induce cell cycle arrest and apoptosis in human ovarian cancer cells [29].…”