Anti-Tumor Effects of Flavonoids from the Ethnic Medicine Docynia delavayi (Franch.) Schneid. and Its Possible Mechanism

Abstract

This study investigated the active components and the anti-tumor efficacy and mechanisms of the flavonoids from Docynia delavayi (Franch.) Schneid. (DDS). MTT assay was used to examine the growth inhibitory effects of the four flavonoids, including chrysin, quercetin, naringenin, and avicularin that were isolated from the rhizome of DDS, on human hematomas cell (HepG2), esophageal carcinoma cell (EC109), human cervical adenocarcinoma cell (Hela), human colon adenocarcinoma cell (SW480), and African green monkey kidney cell (Vero cells). The anti-tumor mechanism of chrysin on HepG2 was further investigated by the methods of fluorescence staining, flow cytometry, and immunoblotting. The results showed that the inhibitory activity of chrysin was much stronger than the other three flavonoids on HepG2, EC109, Hela, and SW480 cells for 48 h treatment in vitro. Moreover, no inhibiting effect of chrysin on the proliferation of normal cells (Vero cells) was observed. Further study revealed that chrysin caused HepG2 cell shrinkage, membrane blebbing, and apoptotic body formation, all of which were typical characteristics of apoptosis programmed cell death. Flow cytometric analysis demonstrated that chrysin increased the sub G0/G1 population, which indicated the increased cell apoptosis, thus preventing cells from entering the S phase as the population in G2/M or S phase declined; whereas in G0/G1 phase, it increased. In addition, immunoblot results showed that chrysin significantly increased the expression levels of caspase-3 and Bax proteins, and it decreased the expression level of B-cell lymphoma/leukemia-2 (Bcl-2) protein. These findings indicate that chrysin is the major flavonoid present in DDS, and it induces HepG2 cell death via apoptosis, probably through the participation of caspase-3, Bax, and Bcl-2 proteins.

Metformin Induced AMPK Activation, G0/G1 Phase Cell Cycle Arrest and the Inhibition of Growth of Esophageal Squamous Cell Carcinomas In Vitro and In Vivo

“…This study was approved and monitored by the Ethics Committees of the First Affiliated Hospital of Shantou Medical University. Human esophageal squamous cell carcinoma cell lines, EC109 [ 18 , 19 ] and EC9706 [ 20 , 21 ], were obtained from the Chinese Academy of Sciences and from The Cell Bank of Type Culture Collection of Chinese Academy of Sciences (CAS, Shanghai). Cells (1 × 10 5 ) were grown in RPMI1640 medium (ICN; Biomedicals Inc.) supplemented with 10% fetal calf serum, 100 units/ml penicillin and 100 units/ml streptomycin (Invitrogen).…”

Characteristic Features of Cytotoxic Activity of Flavonoids on Human Cervical Cancer Cells

“…Flavonoids constitute a class of more than 4000 phenylbenzopyrones and even minor modifications in their structure can be responsible for strong variations in the spectrum of biological activities (Cherng et al, 2007;Mamadalieva et al, 2011). These compounds possess multiple anticancer effects including antioxidant activity, antiproliferation, cell cycle arrest, promotion of apoptosis, modulation of signal transduction pathways and regulation of hormone receptors, inhibition of cancer cell migration, invasion and angiogenesis, and reversal of multidrug resistance (Totta et al, 2004;Kanno et al, 2005;Yang et al, 2009;Chen et al, 2013a;Ramesh and Alshatwi, 2013;Deng et al, 2014;Hu et al, 2014). The selectivity of flavonoids on their molecular targets is probably much higher than previously expected making these compounds very interesting lead structures for the development of novel chemotherapeutic agents (Mamadalieva et al, 2011).…”

“…Although the treatment of human cervical cancer cells (positive for HPV16 or HPV18) with widespread dietary flavanones including fruit flavonoids hesperetin, naringenin and naringin can lead to a dose-and timedependent inhibition of proliferation (see Table 2), this activity reveals only at rather high concentrations (usually more than 100μM) and there are no cytotoxic effects on the cell viability at lower doses (Virgili et al, 2004;Kanno et al, 2005;Liu et al, 2011;Kim et al, 2012;Xie SR et al, 2012;Alshatwi et al, 2013;Ramesh and Alshatwi, 2013;Deng et al, 2014). This anticancer action occurs through induction of cell cycle arrest and promotion of apoptosis.…”

Molecular mechanisms of ampelopsin from Ampelopsis megalophylla induces apoptosis in HeLa cells

“…In the intrinsic pathway, caspase activation is associated with permeabilization of the outer mitochondrial membrane by pro-apoptotic members of the B-cell lymphoma (Bcl) family ( 11 ). Upon disruption of the outer mitochondrial membrane, a set of proteins, typically located in the space between the inner and outer mitochondrial membranes, are released, including cytochrome c (Cyt- c ), second mitochondria-derived activator of caspases/direct inhibitor of apoptosis-binding protein with low pI and apoptosis-inducing factor ( 12 , 13 ). The mitochondrial pathway served a function in the death of tumor cells and is suggested to be the primary underlying molecular mechanism of cancer cell death.…”