Background: HAUS6 participates in microtubule-dependent microtubule amplification, but its role in malignancies including colorectal cancer (CRC) has not been explored. We therefore assessed the potential oncogenic activities of HAUS6 in CRC.Results: HAUS6 mRNA and protein expression is higher in CRC tissues, and high HAUS6 expression is correlated with shorter overall survival in CRC patients. HAUS6 knockdown in CRC cell lines suppressed cell growth in vitro and in vivo by inhibiting cell viability, survival and arresting cell cycle progression at G0/G1, while HAUS6 over-expression increased cell viability. We showed that these effects are dependent on activation of the p53/p21 signalling pathway by reducing p53 and p21 degradation. Moreover, combination of HAUS6 knockdown and 5-FU treatment further enhanced the suppression of cell proliferation of CRC cells by increasing activation of the p53/p21 pathway.Conclusion: Our study highlights a potential oncogenic role for HAUS6 in CRC. Targeting HAUS6 may be a promising novel prognostic marker and chemotherapeutic target for treating CRC patients.
Cell division cycle associated 5 (CDCA5) is implicated in the development and progression of a variety of human cancers. Functional significance of CDCA5 in colorectal cancer (CRC), however, has not been investigated. Using a combination of on-line data mining, biochemistry, and molecular biology, we examined the potential oncogenic activity of CDCA5 and the underlying mechanisms. Experiments with human tissue sample showed increased CDCA5 expression in CRC vs. in noncancerous adjacent tissue, and association of CDCA5 upregulation in CRC tissues with shorter patient survival. Also, representative CRC cell-lines had higher CDCA5 expression vs. fetal colonic mucosal cells. CDCA5 knockdown using lentivirus-mediated shRNA inhibited the proliferation and induced apoptosis in cultured HCT116 and HT-29 cells, and suppressed the growth of xenograft in nude mice. CDCA5 knockdown decreased the expression of CDK1 and CyclinB1, increased caspase-3 activity, cleaved PARP and the Bax/Bcl-2 ratio. CDCA5 knockdown also significantly decreased phosphorylation of ERK1/2 and expression of c-jun. Taken together, these findings suggest a significant role in CRC progression of CRC, likely by activating the ERK signaling pathway.
Shexiang Tongxin dropping pill (STP) is a traditional Chinese medicine formula that consists of total saponins of ginseng, synthetic Calculus bovis, bear gall, Venenum bufonis, borneol and Salvia miltiorrhiza. STP has been widely used in China and Southeast Asia for the treatment of cardiovascular diseases. In this study, a qualitative analytical method using high performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry was developed for identification of the major constituents in STP. Based on the retention time and MS spectra, 41 components were identified by comparison with reference compounds and literature data. Moreover, using ultra-performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry in multiple-reaction monitoring mode, we quantified 13 of the identified constituents (ginsenoside Rg1, ginsenoside Rk3, cinobufagin, arenobufagin, bufalin, resibufogenin, tanshinone IIA, taurine, tauroursodeoxycholic acid, taurocholic acid, cholic acid, deoxycholic acid, and chenodeoxycholic acid). These results suggest that this new approach is applicable for the
OPEN ACCESSMolecules 2015, 20 18598 routine analysis and quality control of STP products and provides fundamental data for further in vivo pharmacokinetical studies.
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