Danshen, derived from the dried root or rhizome of Salviae miltiorrhizae BGE., has Tanshinone IIA (TSA) as one of its active ingredients. Recent reports have shown that TSA can inhibit the apoptosis induced by serum withdrawal or ethanol in cultured PC12 cells. However, whether TSA has any neuroprotective effect remains unknown. In this study, we investigated the effects of TSA on cerebral apoptosis induced by middle cerebral artery occlusion (MCAO) in which cerebral ischemia had been induced 2 h earlier. Twenty-four hours after reperfusion, the rats were assessed for infarct volume etc. Intraperitoneal administration of 25 and 40 mg/kg TSA 10 min after MCAO significantly diminished infarct volume and brain water content and improved neurological deficits in a dose-dependent manner. The 25 mg/kg dosage was more effective. Treatment with 25 mg/kg TSA significantly improved symptoms and reduce infarct volume at different points in time, of which 10 min after MCAO was the most significant. Nissl-staining and HE-staining of the 25 mg/kg TSA group were more appreciable in terms of improvement relative to the vehicle group in the infarct core. TSA of dosage 25 mg/kg significantly decreased the expression of cleaved caspase-3 protein and increased the expression of B-cell lymphoma 2 (bcl-2) protein in the ischemic cortex. Fewer terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL)-positive cells were found in the penumbra of the treated group, but they were significantly more common in the vehicle group. We here conclude that the neuroprotective effects of TSA against focal cerebral ischemic/reperfusion injury are likely to be related to the attenuation of apoptosis.

Today, the number of cancer patients throughout the world is increasing alarmingly and as per the World Health Organisation (WHO) data and statistics the prediction for the year 2020 will be 15 million new cases as compared to only 10 million cases in year 2000 leaving us dumbfounded. A lot of effort has been put in by researchers and scientists over decades to find drugs helpful in the treatment of cancers for the benefit of patients--the latest being the Poly ADP-ribose polymerase (PARP) and the Poly ADP-ribose glycohydrolase (PARG) inhibitors. This review highlights their mechanism of action under the rationale of their use and current development in the field of cancer.

Poly ADP-ribose polymerase (PARP) which is closely related to Poly ADP-ribose glycohydrolase (PARG) has already been thoroughly investigated in both experimental and clinical cancer trials compared to the latter. Nevertheless, in this experiment the importance of PARG expression was highlighted; whereby it is being silenced via lentivirus vector-mediated short hairpin RNA (shRNA). MTT assay showed that there was an inhibition in human Lovo colon cancer cell growth and flow cytometry demonstrated an increase in the population of cells in G(0)/G(1) phase with a decrease in the S phase in transfected Lovo cells. Furthermore, our results suggested that the effect of silencing PARG leads to the inhibition of PARP expression; related to a decrease in the expression of Nuclear Factor Kappa-B (NFκ-B) with an increase in Akt(473) phosphorylation; suggesting that the Phosphoinositol 3-kinase (PI3K)/Akt/NFκ-B pathway is important for cellular growth and proliferation. Hence, this study emphasizes and converges on the relevance of silencing PARG which inhibits growth of human colonic cancer cells via PI3K/Akt/NFκ-B pathway; as colon carcinoma remains to be amongst one of the commonest cancers throughout the world with high morbidity and mortality rates.

Aims: To investigate the role and mechanism of PARG inhibition of metastatic behavior in colonic carcinoma cells. Methods: We examined the effects of PARG protein knockdown by RNA interference on invasion, migration and matrix adhesion of colon carcinoma cell lines in vitro and using a murine in vivo model of liver metastasis. Metastasis related genes were detected using mRNA and protein levels. Moreover, LY294002, an Akt phosphorylation inhibitor, was used to determine whether the suppression of metastatic behavior of colon carcinoma cells was mediated by Akt phosphorylation that was confirmed by EMSA. Pyrrolidine dithiocarbamate (PDTC) was used as a selective NFĸ-B inhibitor to clarify the relationship between PARG, PARP and NF-ĸB. Results: PARG protein was undetectable following specific shRNA transfection; mRNA and protein levels of PARP were significantly decreased. PARG-shRNA cells showed high levels of phosphorylated Akt with decreased expression of NF-ĸB (both total & nuclear), MMP2 and MMP9. However, no additional changes were noted following inhibition of PI3K/Akt pathway by LY294002 in the PARG-shRNA cells; these cells displayed reduced number of liver metastases when characterized in the murine in vivo model. Conclusion: PARG knockdown, concomitant with inhibition of PARP, suppressed the metastatic potency of colon carcinoma cells by activation of PI3K/Akt signaling pathway.

Novel hydrophilic docetaxel analogue (CQMU-0519) inhibited cell proliferation and enhanced the intrinsic apoptotic pathway in lung and ovarian carcinoma cells, whereas it used the extrinsic one in breast adenocarcinoma cells.