Biogenic selenium and its hepatoprotective activity.

Elemental selenium nanoparticles (SeNPs) have multiple biological activities. In this study, we investigated the protective effects of biogenic SeNPs (BioSeNPs) on CCl4-induced liver damage in mice. The results showed that: (i) when compared to sodium selenite (SS), BioSeNPs has a similar tissue distribution after intragastrical administration to mice; (ii) BioSeNPs and SS showed comparable efficacy in increasing the activities of glutathione peroxidase and thioredoxin reductase in liver cell lines, mice blood and liver; (iii) pretreatment with BioSeNPs inhibiting the elevation of activities of various enzymes significantly which included aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, lactate dehydrogenase and liver lipid peroxide (p < 0.05 or p < 0.01) in CCl4-treated mice; (iv) activities of antioxidant enzymes (superoxide dismutase, catalase, and glutathione peroxidase) were significantly increased (p < 0.05 or p < 0.01) after a pretreatment with BioSeNPs in CCl4-treated mice; (v) histopathological damages in the liver from CCl4-treated mice were ameliorated by a pretreatment with BioSeNPs. In conclusion, these results have shown that BioSeNPs is able to protect the liver from CCl4-induced hepatic damage via increasing the antioxidant capacity and inhibiting oxidative damage. BioSeNPs may have the potential to be used as a trace element food supplement inducing antioxidant bioactivities.

Functional proteomic analysis revels that the ethanol extract of Annona muricata L. induces liver cancer cell apoptosis through endoplasmic reticulum stress pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Annona muricata L. is used to treat cancer in some countries. Extracts of Annona muricata have been shown to cause apoptosis of various cancer cells in vitro, and inhibit tumor growth in vivo in animal models. However, the molecular mechanisms underlying its anti-cancer and apoptotic effects of the herb remain to be explored. AIM OF STUDY: The study investigated the molecular mechanisms underlying liver cancer cell apoptosis triggered by the ethanol extract of leaves of Annona muricata L. MATERIALS AND METHODS: Liver cancer HepG2 cells were used as experimental model. MTT assay was employed to evaluate cell viability. Flow cytometry and TUNEL assays were performed to confirm apoptosis. We employed functional proteomic analysis to delineate molecular pathways underlying apoptosis triggered by the herbal extract. RESULTS: We showed that the extract was able to reduce viability and trigger apoptosis of the cancer cells. Proteomic analysis identified 14 proteins associated with the extract-elicited apoptosis, which included the increased expression levels of HSP70, GRP94 and DPI-related protein 5. Western blot analysis confirmed that the extract did up-regulated the protein levels of HSP70 and GRP94. Results from bioinformatic annotation pulled out two molecular pathways for the extract, which, notably, included endoplasmic reticulum (ER) stress which was evidenced by the up-regulation of HSP70, GRP94 and PDI-related protein 5. Further examinations of typical protein signaling events in ER stress using western blot analysis have shown that the extract up-regulated the phorsphorelation of PERK and eIF2α as well as the expression level of Bip and CHOP. CONCLUSION: Our results indicate that the ethanol extract of leaves of Annona muricata L. causes apoptosis of liver cancer cells through ER stress pathway, which supports the ethnomedicinal use of this herb as an alternative or complementary therapy for cancer.

Overcome Cancer Cell Drug Resistance Using Natural Products.

Chemotherapy is one of the major treatment methods for cancer. However, failure in chemotherapy is not uncommon, mainly due to dose-limiting toxicity associated with drug resistance. Management of drug resistance is important towards successful chemotherapy. There are many reports in the Chinese literature that natural products can overcome cancer cell drug resistance, which deserve sharing with scientific and industrial communities. We summarized the reports into four categories: (1) in vitro studies using cell line models; (2) serum pharmacology; (3) in vivo studies using animal models; and (4) clinical studies. Fourteen single compounds were reported to have antidrug resistance activity for the first time. In vitro, compounds were able to overcome drug resistance at nontoxic or subtoxic concentrations, in a dose-dependent manner, by inhibiting drug transporters, cell detoxification capacity, or cell apoptosis sensitivity. Studies in vivo showed that single compounds, herbal extract, and formulas had potent antidrug resistance activities. Importantly, many single compounds, herbal extracts, and formulas have been used clinically to treat various diseases including cancer. The review provides comprehensive data on use of natural compounds to overcome cancer cell drug resistance in China, which may facilitate the therapeutic development of natural products for clinical management of cancer drug resistance.

Evidence for Oldenlandia diffusa-evoked cancer cell apoptosis through superoxide burst and caspase activation.

BACKGROUND & OBJECTIVE: Oldenlandia diffusa (Bai Hua She She Cao) is one of the herbs most commonly used in traditional Chinese medicine for treating cancer. Various studies using the herb alone or in combination with other therapy plans have evidenced the effectiveness of the herb in the management of cancers of different tissue origin. However, the mechanisms underlying its anti-cancer activity are unknown. In the present study, we attempted to investigate the apoptotic activity of crude extracts of the herb as well as the possible molecular pathways. METHODS: We incubated human promyelocytic leukemia cell line HL60 cells with ethanol or aqueous extracts of the herb, and determined the levels of intracellular superoxide at 2 and 4 hours as well as caspase activity at 3, 6 and 8 hours using photospectrometry. Cancer cell survival and apoptosis were quantified at 24 hours by using MTT and flow cytometry analyses respectively. RESULTS: We found that it dose-dependently inhibited the cancer cell growth in MTT assay. Flow cytometry analysis revealed that it elicited significant production of sub-G(1) population of the cells, indicating the extract-evoked cell apoptotic death. The LD(50) of the ethanol extract was estimated to be approximately 320 microg/ml. Moreover, treatment of the cancer cells with the ethanol component markedly increased the production of superoxide within few hours. Significant elevation in the protease activities of caspases-2 and -3 were detected at as early as 3 and 6 hours respectively. CONCLUSION: Our results show that the ethanol extract of the herb effectively evokes cancer cell apoptosis, possibly through burst-mediated caspase activation.

Evidence for Oldenlandia diffusa-evoked cancer cell apoptosis through superoxide burst and caspase activation / 中西医结合学报

BACKGROUND & OBJECTIVE: Oldenlandia diffusa (Bai Hua She She Cao) is one of the herbs most commonly used in traditional Chinese medicine for treating cancer. Various studies using the herb alone or in combination with other therapy plans have evidenced the effectiveness of the herb in the management of cancers of different tissue origin. However, the mechanisms underlying its anti-cancer activity are unknown. In the present study, we attempted to investigate the apoptotic activity of crude extracts of the herb as well as the possible molecular pathways. METHODS: We incubated human promyelocytic leukemia cell line HL60 cells with ethanol or aqueous extracts of the herb, and determined the levels of intracellular superoxide at 2 and 4 hours as well as caspase activity at 3, 6 and 8 hours using photospectrometry. Cancer cell survival and apoptosis were quantified at 24 hours by using MTT and flow cytometry analyses respectively. RESULTS: We found that it dose-dependently inhibited the cancer cell growth in MTT assay. Flow cytometry analysis revealed that it elicited significant production of sub-G(1) population of the cells, indicating the extract-evoked cell apoptotic death. The LD(50) of the ethanol extract was estimated to be approximately 320 microg/ml. Moreover, treatment of the cancer cells with the ethanol component markedly increased the production of superoxide within few hours. Significant elevation in the protease activities of caspases-2 and -3 were detected at as early as 3 and 6 hours respectively. CONCLUSION: Our results show that the ethanol extract of the herb effectively evokes cancer cell apoptosis, possibly through burst-mediated caspase activation.