Physcion 8-O-β-glucopyranoside Research Articles

Physcion 8-O-β-glucopyranoside ameliorates liver fibrosis through inflammation inhibition by regulating SIRT3-mediated NF-κB P65 nuclear expression

Physcion 8-O-β-glucopyranoside (PSG), an anthraquinone extracted from Rumex japonicus Houtt, has various pharmacological effects, however, the effect of PSG on liver fibrosis and its related mechanism remain to be determined. We here showed that PSG ameliorated liver injury and liver fibrosis, decreased collagen deposition and inhibited inflammation in carbon tetrachloride (CCl4)-induced rats. Consistent with the in vivo results, PSG suppressed the transforming growth factor-β1 (TGF-β1)-induced cell viability, liver fibrosis and secretion of inflammatory factors in hepatic stellate cells (HSCs). Interestingly, PSG increased the enzyme activity and promoter activity of sirtuin 3 (SIRT3) in fibrotic liver and activated HSCs. In addition, PSG notably increased the mRNA and protein expression of SIRT3 both in vivo and in vitro. Depletion of SIRT3 either by using 3-TYP (SIRT3 selective inhibitor) or SIRT3 siRNA attenuated the anti-inflammatory effect of PSG in activated HSCs. Further study found that TGF-β1 increased the nuclear expression of NF-κB p65, but showed no obvious effect on the total NF-κB p65 expression. Compared to the control adenovirus (Ad.mk), overexpression of SIRT3 by infecting adenovirus encoding SIRT3 (Ad.SIRT3) notably decreased the nuclear expression of NF-κB p65 in activated HSCs. Our results demonstrated that PSG attenuated inflammation by regulating SIRT3-mediated NF-κB P65 nuclear expression in liver fibrosis, providing novel molecular insights into the anti-fibrotic effect of PSG.

Physcion 8-O-β-glucopyranoside exerts carcinostasis ability in Ishikawa cells via regulating lnc-SLC4A1-1/H3K27ac/NF-κB pathway.

This study aimed to investigate whether physcion 8-O-β-glucopyranoside (PG) exerted anti-tumor effects in endometrial cancer cells via regulating the long non-coding RNA lnc-SLC4A1-1. The anti-tumor effects of PG on endometrial cancer by evaluating Ishikawa cell growth and metastasis, and the expression of lnc-SLC4A1-1 was determined after PG treatment. Subsequently, the role and regulatory mechanism of lnc-SLC4A1-1 dysregulation in PG-treated endometrial cancer cells were explored. PG treatment resulted in dramatical depression of cell viability, remarkable promotion of cell apoptosis and dramatic suppression of migration and invasion in Ishikawa cells in a dose-dependent way. Moreover, PG decreased the level of lnc-SLC4A1-1, and high levels of lnc-SLC4A1-1 reversed the effects of PG on Ishikawa cells. Furthermore, lnc-SLC4A1-1 was transcriptionally activated by H3K27ac and interacted with NF-κB p65 in Ishikawa cells. PG treatment depressed the NF-κB signal in Ishikawa cells, which were significantly reversed after overexpression of lnc-SLC4A1-1. Our results indicate that PG exerts anti-tumor activity in endometrial cancer cells. Lnc-SLC4A1-1/H3K27ac/NF-κB pathway may be a possible mechanism to mediate the anti-tumor effects of PG, which provide a promising targeted strategy for treatment of endometrial cancer.

RETRACTED ARTICLE: Physcion 8-O-β-glucopyranoside mediates the NLRP3-associated pyroptosis and cell metastasis in the human osteosarcoma cells via ER stress activation.

To explore the antitumor effects of physcion 8-O-β-glucopyranoside (PG) on cell pyroptosis and metastasis in the human osteosarcoma (OS) cells and its underlying mechanisms of action. Human OS cell lines HOS and SAOS-2 cells were used in the present study. Cell viability was examined by the CCK-8 assay. Matrigel invasion and TUNEL staining assays were used to analyze cell invasion ability and pyroptosis. The expressions of pyroptosis, EMT, NLRP, and ERS-related proteins were assessed by western blot. Xenograft OS mice model was used for the in vivo experiments. Administration of PG (0 μM, 10 μM, 20 μM) significantly reduced the cell viability of the HOS and the SAOS-2 cells, while promoting the pyroptosis of these cells. PG showed a dose-dependent inhibition of the invasion and metastasis of the OS cells. However, inhibition of NLPR3 and the ER stress maker CHOP restored the effect of PG on pyroptosis and cell metastasis, suggesting that the PG-induced antitumor effects on the HOS and the SAOS-2 cells were mediated by the ER stress-activated NLRP3 inflammasome. Further, the in vivo experiments showed that PG reduced both tumor growth and invasion in the xenograft OS mice model. The results provide valuable insight into the possible underlying mechanisms of PG effects in the human osteosarcoma cells which could be used as a potential anticancer drug for OS treatment.

Physcion 8-O-β-glucopyranoside inhibits testicular germ cell tumors through regulating microRNA-199a.

Testicular germ cell tumors (TGCTs) are frequently diagnosed solid tumors in young adult males. The present study aimed to investigate the anti-tumor function of Physcion 8-O-β-Glucopyranoside (PG) in TGCTs, and to explore the underlying anti-tumor mechanism of PG in TGCTs. Cell viability was measured by a cell counting kit-8 (CCK-8) assay, and the cell cycle distribution was analyzed by flow cytometry. Cell apoptosis was measured using TUNEL staining and flow cytometry. The lactate dehydrogenase (LDH) release, glucose consumption, lactate production, and ATP generation were determined using a Flex Bioanalyzer. The expression of miR-199a was measured by qRT-PCR, and the expression of marker proteins were analyzed by western blotting. Moreover, a xenograft mouse model was used for investigating PG's antitumor effect in vivo. The results showed that PG significantly inhibited NTERA2 and NCCIT cell proliferation, blocked the cell cycle, and induced cell apoptosis. Furthermore, PG suppressed LDH release, glucose consumption, lactate production, and ATP generation in NTERA2 and NCCIT cells. The results of investigating the molecular mechanism of PG in TGCTs showed that miR-199a was decreased in TGCTs but was increased by PG in a dose-dependent manner. MiR-199a knockdown significantly increased NTERA2 and NCCIT cell proliferation, decreased the apoptotic cell rates, and promoted LDH release, glucose consumption, lactate production, and ATP generation. The effects of PG on TGCTs were reversed by miR-199a silencing. In addition, we found that PG significantly inhibited tumor growth in vivo. In conclusion, our study revealed that PG modulated cell proliferation, the cell cycle, apoptosis, and glucose metabolism in TGCTs through regulating miR-199a. These findings indicate a novel therapeutic strategy and a potential biomarker for TGCT treatment.

Physcion 8-O-β-Glucopyranoside Alleviates Oxidized Low-Density Lipoprotein-Induced Human Umbilical Vein Endothelial Cell Injury by Inducing Autophagy Through AMPK/SIRT1 Signaling.

Vascular endothelial cell dysfunction plays a crucial role in the initiation and development of atherosclerosis. Physcion 8-O-β-glucopyranoside (PG), an anthraquinone extracted from Polygonum cuspidatum, has a number of pharmacological functions. The aim of this study was to elucidate the protective effects of PG against oxidized low-density lipoprotein (ox-LDL) in VECs. Human umbilical vein endothelial cells (HUVECs) were used as the in vitro model. Cell viability and apoptosis were, respectively, assessed by CCK-8 assay and Annexin-V/PI staining. Formation of autophagosomes was visualized by acridine orange staining, and the autophagy flux was tracked after infecting the cells with the mRFP-GFP-LC3 adenovirus. The expression levels of various apoptosis and autophagy-associated marker proteins were detected by Western blotting. Pretreatment with PG protected the HUVECs from ox-LDL-induced apoptosis. In addition, PG promoted autophagy in HUVECs, which was responsible for its antiapoptotic effects. Finally, activation of AMPK/SIRT1 signaling was upstream of PG-induced autophagy. PG has potential pharmacological effects against oxidative damage-induced HUVEC injury through inducing AMPK/SIRT1-mediated autophagy.

Physcion 8-O-β-glucopyranoside exhibits anti-growth and anti-metastatic activities in ovarian cancer by downregulating miR-25.

Ovarian cancer ranks 5th leading cause of cancer-related death in females worldwide. Physcion 8-O-β-glucopyranoside (PG) is an anthraquinone compound isolated from Rumex japonicus Houtt. This study aimed at investigating the effect of PG on ovarian cancer cells. Cell viability was detected by CCK-8 assay. Colony formation assay evaluated whether PG could affect anchorage-independent growth. Whether PG affected cell cycle progression was examined by flow cytometry. The morphological changes caused by PG were visualized by microscopy. Apoptosis was quantitatively analyzed by flow cytometry. The effect of PG on cell migration and invasion was assessed by wound healing and transwell, respectively. The effect of PG on the expression of molecular markers was determined by Western blot. Microarray assay was performed to identify the potential target of PG. Results from the present study showed that PG decreased ovarian cancer cells viability. Colony formation assay also showed that PG suppressed the anchorage-independent growth of SKOV3 and OVCAR-3 cells. PG triggered cell cycle arrest at G1/G0 phase. The pro-apoptotic activity of PG was confirmed by flow cytometry, activation of caspase-3 and PARP, upregulation of Bax and downregulation of Bcl-2. The ability of PG to inhibit migration and invasion was evidenced by a decrease in wound healing and invasive cell number, as well as downregulation of MMP-2 and upregulation of TIMP-3. Microarray and qRT-PCR showed that miR-25 expression was downregulated by PG treatment. Moreover, our results indicated that the anti-cancer activities of PG were augmented by miR-25 knockdown and attenuated by ectopic miR-25 expression. PG exhibited anti-cancer activity in ovarian cancer by downregulating miR-25.

Physcion 8-O-β-Glucopyranoside Exerts Anti-Tumor Activity Against Non-Small Cell Lung Cancer by Targeting PPARγ.

Lung cancer is one of the most common causes of cancer related mortality. The present study is designed to investigate whether a naturally occurring anthraquinone compound, physcion 8-O-β-glucopyranoside (PG) could exert anti-cancer activity against non-small cell lung cancer (NSCLC). Cell viability was determined by Cell Counting Kit-8 (CCK-8) assay. Cell cycle distribution and cell apoptosis were determined by flow cytometry. Expressions of marker proteins were assessed by western blot analysis. To examine the role of PPARγ (peroxisome proliferator-activated receptor γ) in PG-induced apoptosis and cell cycle arrest, PPARγ was knockdown using siRNA. In addition, a xenograft model was established to investigate the effect of PG in vivo. The results showed that PG markedly induced cell cycle arrest and apoptosis in human NSCLC cell lines A549 and H358. The anti-tumor effect of PG in NSCLC cells was mediated by upregulation of PPARγ. Besides, in NSCLC cell lines, the anti-cancer activity of PG was also examined in the xenograft mice model, which showed that PG could significantly reduce tumor burden and activate apoptotic signaling. Our results demonstrated that PG can be regarded as a candidate chemotherapeutic agent for lung cancer. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc. Anat Rec, 302:785-793, 2019. © 2018 Wiley Periodicals, Inc.

Physcion 8‑O‑β‑glucopyranoside extracted from Polygonumcuspidatum exhibits anti‑proliferative and anti‑inflammatory effects on MH7A rheumatoid arthritis‑derived fibroblast‑like synoviocytes through the TGF‑β/MAPK pathway.

The present study aimed to investigate the anti-arthritic effect of physcion 8-O-β-glucopyranoside (POGD) and its possible mechanisms. The anti-proliferative effects of POGD on MH7A cells were detected using a CCK-8 assay, and the release of pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, IL-8, IL-12 and IL-17A, were determined by ELISA. A type II collagen-induced arthritis (CIA) rat model was established to evaluate the anti-arthritic effect of POGD in vivo. The paw volumes, arthritis indices and serum levels of tumor necrosis factor (TNF)-α, IL-1β, IL-6, IL-8, IL-17A were determined by ELISA. The mRNA expression levels of matrix metalloproteinase (MMP)-2, MMP-3, MMP-9, vascular endothelial growth factor and cyclooxygenase-2 were determined by reverse transcription-quantitative polymerase chain reaction analysis, and the expression levels of transforming growth factor (TGF)-β1, small mothers against decapentaplegic (Smad)4, Smad7, c-Jun N-terminal kinase (JNK), phosphorylated (p-)JNK, p-P38, P38, p-extracellular signal-regulated kinase (ERK)1/2, ERK1/2, nuclear factor (NF)-κB p65 in the nucleus (N), cytosolic NF-κB p65 (C), and inhibitor of NF-κB (IκB) were determined by western blot analysis. The results indicated that POGD significantly inhibited MH7A cell growth. POGD markedly inhibited paw swelling and the arthritis indices of the CIA rats, and POGD may also inhibit the release of pro-inflammatory cytokines. Furthermore, POGD downregulated the expression levels of TGF-β1, Smad4, NF-κB p65 (N), p38, p-p38, p-ERK1/2, JNK, p-JNK, TGF-β1, Smad4, p-JNK, JNK, p-P38, P38, p-ERK1/2, ERK1/2 and NF-κB p65 (N), and upregulated the Smad7, NF-κB p65 (C) and IκB in TNF-α induced MH7A cells. In conclusion, the results suggested that POGD is a promising potential anti-inflammatory drug, and that POGD may decrease the expression of pro-inflammatory cytokines and mediators via inhibiting the TGF-β/NF-κB/mitogen-activated protein kinase pathways.

Physcion 8-O-β-glucopyranoside exhibits anti-leukemic activity through targeting sphingolipid rheostat.

Acute lymphoblastic leukemia (ALL) is the most common fatal cancer in people younger than 20 years of age. This study was designed to explore the anti-leukemia activity of physcion 8-O-β-glucopyranoside (PG) in B-cell ALL. NALM6 and SupB15 cells were used as model cell lines. Cell viability, cell apoptosis, cell cycle distribution were determined by CCK-8 assay, DNA fragmentation assay and flow cytometry, and flow cytometry, respectively. Expression of proteins involved in cell apoptosis and cell cycle regulation was determined by western blot and the levels of ceramide and sphingosine 1-phosphate (S1P) were determined by ELISA. Activity of sphingosine kinase 1 (SphK1) was also determined with a Sphingosine Kinase Assay Kit. In the present study, both model cell lines were transfected with siRNA targeting SphK1 or an overexpression plasmid to examine the role of SphK1 in the anti-leukemia activity of PG. Moreover, the efficacy of PG was examined in vivo in a mouse model by measuring survival and spleen weight. Our results provided experimental evidence that PG could significantly induce apoptosis and cell cycle arrest in vitro. Mechanistically, the anti-leukemia activity of PG was mediated by its ability to repress SphK1 and thus modulate ceramide-S1P rheostat. Moreover, the anti-leukemia activity of PG was also verified in a murine model. Collectively, our results indicate that PG may be a promising agent for the treatment of B-cell leukemia.

In vivo and in vitro anti-sepsis effects of physcion 8-O-β-glucopyranoside extracted from Rumex japonicus

The present study was designed to investigate the anti-sepsis effects of physcion 8-O-β-glucopyranoside (POG) isolated from Rumex japonicas and explore its possible pharmacological mechanisms. POG was extracted from R. japonicas by bioactivity-guided isolation with the anti-sepsis agents. Survival analysis in septic mouse induced by LPS and heat-killed Escherichia coli were used to evaluate the protective effect of POG (40 mg·kg−1, i.p.) on sepsis. Cytokines including TNF-α, IL-1β and IL-6 in RAW 264.7 cells induced by LPS (100 ng·mL−1) were determined by ELISA. In addition, the proteins expressions of TLR2 and TLR4 were determined by Western blotting assay. Our results demonstrated that POG (40 mg·kg−1, i.p.) possessed significant protective activity on the endotoxemic mice. The POG treatment (20, 40, and 80 μg·mL−1) significantly decreased the TNF-α, IL-1β and IL-6 induced by LPS (P < 0.01) in a concentration-dependent manner. Furthermore, the TLR4 and TLR2 proteins were also down-regulated by POG at 20 (P < 0.01), 40 (P < 0.01), and 80 μg·mL−1 (P < 0.01). The present study demonstrated that the POG extracted from R. japonicas possessed significant anti-sepsis effect on endotoxemic mice, and can be developed as a novel drug for treating sepsis in the future.

Physcion 8-O-β-glucopyranoside suppresses the metastasis of breast cancer in vitro and in vivo by modulating DNMT1.

The present study is designed to explore the metastasis-inhibitory effect of physcion 8-O-β-glucopyranoside (PG) in human breast cancer, and the mechanisms underlying its role in tumor metastasis. Both in vitro and in vivo studies were conducted. Cell migration and invasion were analyzed by transwell assay. The translocation of β-catenin from the nucleus to cytoplasm membrane was demonstrated by immunofluorescent staining. The expression of signaling molecules was determined by Western blot or qRT-PCR. The present study showed that PG suppressed the migration, invasion, and EMT of breast cancer cells MDA-MB-231 in a dose-dependent manner. The results also revealed that impairment of the metastatic potential caused by PG was associated with the activation of AMPK and downregulation of both DNMT1 and Sp1. Moreover, the data from the in vivo model also supported the in vitro findings, which showed that inhibition of metastasis by PG was associated with the downregulation of DNMT1 and Sp1 as well as increased level of phosphorylated AMPK. The present study showed that PG could suppress the metastasis of breast cancer, which highlighted a novel pharmacological application of this compound. Given the aggressive properties of breast cancer, the current study suggests that PG can serve as a safe therapeutic agent for suppressing breast cancer metastasis, although additional data is necessitated.

Antitumor activity of physcion 8-o-β-glucopyranoside against cervical cancer by induction of apoptosis

Purpose: To investigate the antitumor activity of physcion8-O-β-glucopyranoside (PSG) against cervical cancer, as well as its mechanisms.Methods: The anti-proliferative effects of PSG on HeLa cells were determined by CCK-8 assay and the half maximal inhibitory concentration (IC50) values were calculated. Subsequently, a mouse xenograft model of HeLa cell line was established to investigate the antitumor effect of PSG in vivo. Furthermore, cell apoptosis was investigated by fluorescence microscopy via DAPI staining, and other mechanisms were determined by Western blot assay.Results: In vitro, PSG exhibited significant anti-proliferative effect on HeLa cells (p &lt;0.05) in concentration-and time-dependent manners, with an IC50 value of 41.34 μg/mL. In vivo, PSG also had significant anti-tumor activity in nude mouse xenograft model (p &lt; 0.05), inhibiting tumor growth. Furthermore, the results showed that treatment with PSG (20, 40 and 60 μg/mL) for 24 h resulted in significantly increased apoptosis in HeLa cells (p &lt; 0.05). Additionally, Western blot analysis revealed that after exposure to 20, 40 and 60 μg/mL of PSG for 24 h, protein expressions of C-caspase-3, Ccaspase-9 and Bax were markedly up-regulated (p &lt; 0.05) while Bcl-2 was significantly down-regulated (p &lt; 0.05). These results confirmed that PSG inhibited HeLa cell growth by inducing mitochondriamediated apoptosis via up-regulation of caspase-3 and caspase-9 and Bax, and down-regulation of Bcl-2.Conclusion: The results demonstrate that PSG possesses notable anti-tumor activity against cervical cancer and that the mechanisms involve induction of apoptosis by mitochondria-mediated signaling pathway.Keywords: Physcion 8-O-β-glucopyranoside, Cervical cancer, Apoptosis, HeLa cells, Caspase, Antitumour, Mouse xenograft

Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human oral squamous cell carcinoma cells via suppressing survivin expression.

A previous study has shown that physcion 8-O-β-glucopyranoside (PG) derived from Rumex japonicusHoutt causes apoptosis and blocks cell cycle progression in human lung cancer cells. In the present study we investigated the molecular mechanisms underlying PG-induced cancer cell apoptosis. Human OSCC-derived cell line KB was treated PG (10, 20, 50 μg/mL). Cell apoptosis was detected with flow cytometry. Mitochondrial membrane potential (MMP) and release of cytochome C from mitochondria were measured; the expression of relevant signaling proteins was analyzed using Western blotting or qRT-PCR. For evaluation of in vivo anticancer action, nude mice grafted with KB cells were treated with PG (10, 20, 40 mg·kg(-1)·d(-1), ip) for 24 days. PG dose-dependently suppressed cell proliferation and induced apoptosis in KB cells. PG-induced apoptosis was mediated via the intrinsic mitochondrial pathway, as evidenced by the decreased Bcl-2, increased Bax and Bax/Bcl-2 ratio, as well as the loss of MMP, caspase-9 activation, and increased cytosolic cytochrome c. Furthermore, PG suppressed the expression of survivin, whereas overexpression of survivin markedly attenuated PG-induced apoptosis. Meanwhile PG increased the expression of tumor suppressor PTEN, and decreased p-Akt, p-GSK3β and miR-21 levels. Pharmacological activation of Akt/GSK3β signaling or transfection with miR-21 mimic abolished PG-induced survivin reduction and cell apoptosis. Similar results were observed in PG-treated nude mice grafted with KB cells. Physcion 8-O-β-glucopyranoside induces mitochondria-dependent apoptosis of human OSCC cells by suppressing survivin expression via miR-21/PTEN/Akt/GSK3β signaling pathway.

Ameliorative effects of physcion 8-O-β-glucopyranoside isolated from Polygonum cuspidatum on learning and memory in dementia rats induced by Aβ1–40

Context: Polygonum cuspidatum Sieb. Et Zucc. (Polygonaceae) has been traditionally used in folk medicine to treat various diseases.Objective: This study investigates the ameliorative effects of physcion 8-O-β-glucopyranoside (PSG) isolated from P. cuspidatum on learning and memory in dementia rats induced by Aβ1–40.Materials and methods: Dementia rats were prepared by intracerebroventricular injection of Aβ1–40. PSG (5, 10, 20, and 40 mg/kg/d, for 5 d) was administered orally. Ameliorative activity of PSG in dementia rats was evaluated by the Morris water maze (MWM) test, and its mechanisms were explored by evaluating AchE activity, levels of DA, NE, and 5-HT in hippocampus, and drebrin protein expressions in hippocampus.Results: Our results indicated that PSG (5, 10, 20, and 40 mg/kg/d) significantly inhibited the prolonged latency in dementia rats (p < 0.05), and inhibitory rates were 16.5, 22.7, 33.0, and 44.8% after 5 d of learning, indicating that PSG improves learning and memory of dementia rats. Furthermore, PSG significantly decreased AchE activity (10, 20, and 40 mg/kg/d; p < 0.05), increased 5-HT (20 and 40 mg/kg/d, p < 0.05), NE (10, 20, and 40 mg/kg/d; p < 0.05), and DA levels (5, 10, 20, and 40 mg/kg; p < 0.05) in the hippocampus. Additionally, PSG obviously decreased the Aβ contents in hippocampus (10, 20, and 40 mg/kg/d; p < 0.05), and up-regulated drebrin protein expressions (5, 10, 20, and 40 mg/kg/d; p < 0.05).Conclusions: PSG can significantly enhance learning and memory in Aβ1–40-induced dementia rats, and the mechanisms may be related to increase levels of Ach, 5-HT, NE, and DA, decrease Aβ contents, and up-regulation of drebrin proteins in hippocampus.

Anti-proliferative of physcion 8-O-β-glucopyranoside isolated from Rumex japonicus Houtt. on A549 cell lines via inducing apoptosis and cell cycle arrest.

BackgroundLung cancers are leading causes of cancer death, and Rumex japonicus has been traditionally used in folk medicine as anti-microorganic, anti-inflammatory and anti-tumor agents. This study was designed to investigate the anti-proliferative activity of physcion 8-O-β-glucopyranoside (PG) isolated from Rumex japonicus Houtt. on A549 cell lines.MethodsIn our present study, PG was isolated and identified from the ethanol extracts of R. japonicus. MTT method was used to evaluate the anti-proliferative activity of PG on A549 cell lines, and cell cycle distribution assay, apoptosis assay, and western blot analysis in vitro were used to explore the possible mechanisms.ResultsFrom the results of our present study, cell viability was obviously inhibited by PG, in a dose- and time-dependent manner. Our results also suggested that the anti-proliferative effect of PG was related to cell cycle arrest at the G2/M phase through repression of cdc2 and Cyclin B1 protein expression. In addition, the results of apoptosis assay and western blot analysis indicated that the anti-proliferative activity could be related to apoptosis via up-regulating the expressions of Bax, caspase-3 and caspase-7, and down-regulating the expressions of Bcl-2.ConclusionsIn conclusion, the PG has significant anti-proliferative activity on A549 cell lines, and the possible mechanism was related to cell cycle arrest at the G2/M phase, and apoptosis via the regulations of Bax, Bcl-2, and caspase-3 and caspase-7.