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Overexpressed gastrin is reported to promote oncogenesis and development of gastric cancer by inhibiting apoptosis of cancer cells; however, the underlying mechanism remains unclear. Our study is aimed at revealing the mechanism underlying the effect of gastrin on apoptosis of gastric cancer cells. Gastrin-interfering cell line was constructed by stably transfecting gastrin-specific pshRNA plasmid to gastric cancer cell line BGC-823. Then, differentially expressed proteins between untreated BGC-823 and gastrin-interfering BGC-823 cell lines were detected by the iTRAQ technique. GO and KEGG analysis was used to analyze the differentially expressed genes that code these differentially expressed proteins. The Annexin V-FITC staining assay was used to detect gastric cancer cell apoptosis. The DCFH-DA fluorescent probe staining assay was used to measure intracellular ROS. Mitochondrial membrane potential was detected by flow cytometry. Western blot was used to analyze the mitochondria respiratory chain proteins and apoptosis-related proteins. A total of 107 differentially expressed proteins were identified by iTRAQ. GO and KEGG analysis showed that proteins coded by the corresponding differentially expressed genes were mainly enriched in the mitochondrial oxidative respiratory chain, and the expression of three proteins (COX17, COX5B, ATP5J) was upregulated. The three proteins with higher scores were verified by Western blot. The apoptosis rate of the gastrin knockdown cancer cell was significantly increased; meanwhile, gastrin knockdown leads to increase of membrane potential and decrease of intracellular ROS production. Additionally, Bax was significantly increased, whereas NF-κB-p65 and Bcl-2 were downregulated after knockdown of gastrin. Concomitantly, pretreatment with NAC reversed the effect of gastrin on the Bax and Bcl-2 expression. Gastrin promotes the production of ROS from mitochondria, activates NF-κB, and inhibits apoptosis via modulating the expression level of Bcl-2 and Bax. [ABSTRACT FROM AUTHOR]

The extract of Broussonetia papyrifera has been proved to have antitumor activity. However, the underlying mechanism remains unclear. This study aimed to elucidate the mechanism of apoptosis of HepG2 cells induced by polyphenols from Broussonetia papyrifera (PBPs). The results revealed that PBPs inhibited the proliferation of HepG2 cells in a dose-dependent and time-dependent manner. Flow cytometry analysis showed that PBPs increased the apoptosis ratio of HepG2 cells significantly. PBPs increased intracellular reactive oxygen species (ROS) production and decreased intracellular superoxide dismutase (SOD) level of HepG2 cells. PBPs induced cell cycle arrest at G1 phase. Western blotting showed that PBPs upregulated the ratio of Bax/Bcl-2 and the expression level of Caspase-3, and activated p53 in HepG2 cells. The inhibition of proliferative relative signals (protein kinase B, PKB/AKT) and survival relative signals (extracellular signal-regulated kinase, ERK) were also observed in PBP-treated HepG2 cells. Our findings suggest that apoptosis of HepG2 cells induced by PBPs is mitochondria-mediated via inactivation of ERK and AKT signaling pathways. [ABSTRACT FROM AUTHOR]

Dendrobium officinale (Tie Pi Shi Hu in Chinese) has been widely used to treat different diseases in China. Anticancer effect is one of the important effects of Dendrobium officinale. However, the molecular mechanism of its anticancer effect remains unclear. In the present study, gastric carcinogenesis in rats was used to evaluate the effect of Dendrobium officinale on cancer, and its pharmacological mechanism was explored. Dendrobium officinale extracts (4.8 and 2.4 g/kg) were orally administered to the rats of the gastric carcinogenesis model. Compared with the cancer model group, the high dose of Dendrobium officinale extracts significantly inhibited the rate of carcinogenesis. Further analysis revealed that Dendrobium officinale extracts could regulate the DNA damage, oxidative stress, and cytokines related with carcinogenesis and induce cell apoptosis in order to prevent gastric cancer. [ABSTRACT FROM AUTHOR]

Breast cancer is considered the most prevalent malignancy due to its high incidence rate, recurrence, and metastasis in women that makes it one of the deadliest cancers. The current study aimed to predict the genes associated with the recurrence and metastasis of breast cancer and to validate their effect on MDA-MB-231 cells. Through the bioinformatics analysis, the transcription factor 7 cofactor (MLLT11) as the target gene was obtained. MLLT11-specific siRNA was synthesized and transfected into MDA-MB-231 cells. The results demonstrated that the siRNA significantly reduced the MLLT11 mRNA levels. Moreover, cell migration and invasion, as well as the protein levels of phosphatidylinositol 3-kinase (PI3K), AKT, matrix metalloproteinase (MMP) 2, and MMP9, were significantly lower in the groups treated with siRNA while the apoptosis was augmented. Collectively, MLLT11 siRNA elicited ameliorative properties on breast cancer cells, possibly via the inhibition of the PI3K/AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Isodon lophanthoides var. gerardianus (Benth.) H. Hara, a native medicinal plant produced chiefly across Southern China, is one of the mainstream varieties of Xihuangcao, which has long been applied in preventing and treating some common liver or gall diseases. Water-soluble total flavonoids (WSTF) extracted from folk herbal medicine have many pharmacological effects. The objective of the paper is to investigate the synergy of WSTF with 5-fluorouracil (5-FU) on HCC and the related mechanisms. Cells were exposed to WSTF alone or combination treatment with 5-FU. Then, in this study, we conducted cell viability test, cell cycle and clone forming test, apoptosis assay, reactive oxygen species (ROS), Western blotting, immunohistochemistry, and a xenograft tumor growth model for investigating the role of WSTF in HCC in vivo and in vitro. It was discovered that WSTF caused cell cycle arrest at the G0/G1 phase while increasing the ROS contents. The generation of ROS levels could cause cell apoptosis and inhibit colony formation. WSTF decreased the Bcl-2 level but promoted the Bax level. These showed the mitochondrial dependence of WSTF-mediated apoptosis. WSTF combined with 5-FU have a synergistic effect to significantly inhibit carcinogenicity in vivo and in vitro. The reduced ROS changed the synergy of WSTF with 5-FU. At last, WSTF inhibit the growth of HCC and promote the HCC sensitivity to 5-FU through ROS accumulation. WSTF-increased ROS levels may partially or completely contribute to enhanced toxicity. WSTF combined with 5-FU in HCC can play a synergistic effect when applied in the clinical setting. [ABSTRACT FROM AUTHOR]

The regulatory effect of luteolin on the progression of Alzheimer's disease (AD) remains unclear from the perspective of apoptosis. The present study aimed to investigate the protective effects of luteolin against Aβ25-35-induced cell apoptosis in pheochromocytoma (PC-12) cells. Aβ25-35 was used to induce an in vitro model of AD. Estradiol was used as a positive control. The PC-12 cells were incubated with luteolin alone or in combination with fulvestrant or U0126. The results showed that luteolin treatment significantly prevents Aβ25-35-induced decrease in cell viability and inhibits Aβ25-35-induced cell apoptosis. After the addition of fulvestrant and U0126, the apoptosis rate of PC-12 cells increased significantly. In addition, luteolin treatment significantly upregulated the expression of Bcl-2 and downregulated the expression of Bax and caspase-3, whereas fulvestrant and U0126 partially reversed the effects of luteolin. Moreover, luteolin treatment upregulated the expression of ERβ and p-ERK1/2, whereas fulvestrant blocked the expression of p-ERK1/2. The study showed that luteolin could activate the ER/ERK/MAPK signalling pathway to protect PC-12 cells against Aβ25-35-induced cell apoptosis via selectively acting on ERβ. Thus, luteolin may be considered as a potential novel therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid 2-related factor 2 (Nrf2) is involved in tumor drug resistance, but its role in imatinib resistance of chronic myeloid leukemia (CML) remains elusive. We aimed to investigate the effects of Nrf2 on drug sensitivity, thioredoxin reductase (TrxR) expression, reactive oxygen species (ROS) production, and apoptosis induction in imatinib-resistant CML K562/G01 cells and explored their potential mechanisms. Stable K562/G01 cells with knockdown of Nrf2 were established by infection of siRNA-expressing lentivirus. The mRNA and protein expression levels of Nrf2 and TrxR were determined by real-time quantitative polymerase chain reaction and western blot, respectively. ROS generation and apoptosis were assayed by flow cytometry, while drug sensitivity was measured by the Cell Counting Kit-8 assay. Imatinib-resistant K562/G01 cells had higher levels of Nrf2 expression than the parental K562 cells at both mRNA and protein levels. Expression levels of Nrf2 and TrxR were positively correlated in K562/G01 cells. Knockdown of Nrf2 in K562/G01 cells enhanced the intracellular ROS level, suppressed cell proliferation, and increased apoptosis in response to imatinib treatments. Nrf2 expression contributes to the imatinib resistance of K562/G01 cells and is positively correlated with TrxR expression. Targeted inhibition of the Nrf2-TrxR axis represents a potential therapeutic approach for imatinib-resistant CML. [ABSTRACT FROM AUTHOR]