Rong-Mei Wang

Curcumin Induces Apoptosis in SGC-7901 Gastric Adenocarcinoma Cells via Regulation of Mitochondrial Signaling Pathways

Curcumin, a polyphenol compound derived from the rhizome of the plant Curcuma longa L. has been verified as an anticancer compound against several types of cancer. However, understanding of the molecular mechanisms by which it induces apoptosis is limited. In this study, the anticancer efficacy of curcumin was investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that curcumin induced morphological changes and decreased cell viability. Apoptosis triggered by curcumin was visualized using Annexin V-FITC/7- AAD staining. Curcumin-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (MMP) and the release of cytochrome c into the cytosol. Furthermore, the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3 and increased cleaved PARP was observed in SGC-7901 cells treated with curcumin. Therefore, curcumin-induced apoptosis of SGC-7901 cells might be mediated through the mitochondria pathway, which gives the rationale for in vivo studies on the utilization of curcumin as a potential cancer therapeutic compound.

Strategies to release doxorubicin from doxorubicin delivery vehicles

Abstract Doxorubicin (DOX) is one of the most effective cytotoxic anticancer drugs and has been successfully applied in clinics to treat haematological malignancies and a broad range of solid tumours. However, the clinical applications of DOX have long been limited due to severe dose-dependent toxicities. Recent advances in the development of DOX delivery vehicles have addressed some of the non-specific toxicity challenges associated with DOX. These DOX-loaded vehicles are designed to release DOX in cancer cells effectively by cutting off linkers between DOX and carriers response to stimuli. This article focuses on various strategies that serve as potential tools to release DOX from DOX-loaded vehicles efficiently to achieve a higher DOX concentration in tumour tissue and a lower concentration in normal tissue. With a deeper understanding of the differences between normal and tumour tissues, it might be possible to design ever more promising prodrug systems for DOX delivery and cancer therapy in the near future.

Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells

Retigeric acid B (RAB), a natural compound isolated from lichen, has been demonstrated to inhibit cell growth and promote apoptosis in prostate cancer (PCa) cells. The present study evaluated the function of RAB combined with clinical chemotherapeutic drugs in PCa cell lines by MTT assay, reverse transcription quantitative polymerase chain reaction and western blot analysis, and identified that RAB at low doses produced significant synergistic cytotoxicity in combination with cisplatin (CDDP); however, no marked synergism between RAB and the other chemotherapeutics was observed. Additional studies revealed that RAB exerted an inhibitory effect on DNA damage repair pathways, including the nucleotide excision repair and mismatch repair pathways, which are involved in the sensitivity to CDDP-based chemotherapy, as suggested by the significantly downregulated expression of certain associated repair proteins. Notably, Excision repair cross-complementing 1, a critical gene in the nucleotide excision repair pathway, exhibited the most significant decrease. When combined with CDDP, RAB-mediated impairment of DNA repair resulted in prolonged DNA damage, as demonstrated by the long-lasting appearance of phosphorylation of histone H2AX at Ser139, which potentially enhanced the chemosensitivity to CDDP. Concurrently, the proapoptotic protein death receptor 5 (DR5) was activated by RAB, which also enhanced the chemotherapeutic response of CDDP. Knockdown of DR5 partially blocked RAB-CDDP synergism, suggesting the crucial involvement of DR5 in this event. The results of the present study identified that RAB functioned synergistically with CDDP to increase the efficacy of CDDP by inhibiting DNA damage repair and activating DR5, suggesting the mechanistic basis for the antitumor effect of RAB in combination with current chemotherapeutics.

Qualitative and quantitative analysis of Yifei Tongluo granules to identify main bioactive components using LC–DAD/MS and pharmacokinetic studies

&NA; A standard fingerprint containing twelve common peaks was constructed from ten batches of Yifei Tongluo granules to evaluate batch‐to‐batch consistency by using HPLC‐DAD. Additionally, the corresponding medicinal material attributes of these chemical constituents were analyzed according to the data acquired from the HPLC method and the identification was further carried out using the LC–MS/MS method. Comparing the retention time or accurate mass with previous studies or standards, the common components were tentatively identified in 50 min for ten batches of samples. At the same time, a reliable LC–MS/MS method was established to quantify marker substances simultaneously in 25 min, and the linear relationship of the standard curves was good in the experimental range. The validations of the method were successfully applied to the quality control and pharmacokinetic study. The results obtained from this study suggest that militarine was most abundant and the components in the granules caused pharmacokinetic herb‐drug interactions in rats. This study provides a meaningful basis for evaluating the viability of Yifei Tongluo granules for clinical applications.

Suppression of the NF‑κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute

Colorectal cancer (CRC) is a major cause of mortality and morbidity. Chronic inflammation is closely associated with the development, progression and prognosis of the majority of intestinal malignancies. In recent years, targeting the nuclear factor (NF)-κB signaling pathway for CRC therapy has become an attractive strategy. Riccardin D, a novel macrocyclicbis (bibenzyl) compound, was isolated from the Chinese liverwort plant. Previous studies have suggested that Riccardin D exerted chemo-preventative effects against the intestinal malignancy formation. In the present study, cell counting kit-8, Hochest 33258 staining, mitochondria membrane permeability assay, western blotting analysis, reverse transcription-polymerase chain reaction, luciferase reporter gene assay and molecular modeling analysis were performed to detect the effect and mechanisms of Riccardin D on human colon cancer cells. The results demonstrated that Riccardin D significantly inhibited the growth of HT-29 cells. In addition, the cDNA expression of cyclooxygenase-2, and the protein expression and activity of NF-κB and tumor necrosis factor-α were downregulated; however, the protein expression of cleaved caspase-3 and −9, and cleaved poly (adenosine diphosphate-ribose) polymerase, and the B-cell lymphoma (Bcl)-2: Bcl-2-associated X protein ratio were upregulated. Furthermore, Auto Dock analysis identified binding sites between Riccardin D and NF-κB. These results indicated that Riccardin D may inhibit cell proliferation and induce apoptosis in HT-29 cells, which may be associated with the blocking of the NF-κB signaling pathway. Thus, Riccardin D should be investigated as an NF-κB inhibitor in cancer therapy.

Acetyl-11-keto-β-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking Akt and Stat3 signaling, thus suppressing chemoresistant stem cell-like properties

Acquired docetaxel-resistance of prostate cancer (PCa) remains a clinical obstacle due to the lack of effective therapies. Acetyl-11-keto-β-boswellic acid (AKBA) is a pentacyclic triterpenic acid isolated from the fragrant gum resin of the Boswellia serrata tree, which has shown intriguing antitumor activity against human cell lines established from PCa, colon cancer, malignant glioma, and leukemia. In this study, we examined the effects of AKBA against docetaxel-resistant PCa in vitro and in vivo as well as its anticancer mechanisms. We showed that AKBA dose-dependently inhibited cell proliferation and induced cell apoptosis in docetaxel-resistant PC3/Doc cells; its IC50 value in anti-proliferation was ∼17 μM. Furthermore, AKBA dose-dependently suppressed the chemoresistant stem cell-like properties of PC3/Doc cells, evidenced by significant decrease in the ability of mammosphere formation and down-regulated expression of a number of stemness-associated genes. The activation of Akt and Stat3 signaling pathways was remarkably enhanced in PC3/Doc cells, which contributed to their chemoresistant stem-like phenotype. AKBA (10–30 μM) dose-dependently suppressed the activation of Akt and Stat3 signaling pathways in PC3/Doc cells. In contrast, overexpression of Akt and Stat3 significantly attenuated the inhibition of AKBA on PC3/Doc cell proliferation. In docetaxel-resistant PCa homograft mice, treatment with AKBA significantly suppresses the growth of homograft RM-1/Doc, equivalent to its human PC3/Doc, but did not decrease their body weight. In summary, we demonstrate that AKBA inhibits the growth inhibition of docetaxel-resistant PCa cells in vitro and in vivo via blocking Akt and Stat3 signaling, thus suppressing their cancer stem cell-like properties.