The role of endolysosomal trafficking in anticancer drug resistance.

Multidrug resistance (MDR) remains a major obstacle towards curative treatment of cancer. Despite considerable progress in delineating the basis of intrinsic and acquired MDR, the underlying molecular mechanisms remain to be elucidated. Emerging evidences suggest that dysregulation in endolysosomal compartments is involved in mediating MDR through multiple mechanisms, such as alterations in endosomes, lysosomes and autophagosomes, that traffic and biodegrade the molecular cargo through macropinocytosis, autophagy and endocytosis.

Bax/Tubulin/Epithelial-Mesenchymal Pathways Determine the Efficacy of Silybin Analog HM015k in Colorectal Cancer Cell Growth and Metastasis.

The inhibition of apoptosis, disruption of cellular microtubule dynamics, and over-activation of the epithelial mesenchymal transition (EMT), are involved in the progression, metastasis, and resistance of colorectal cancer (CRC) to chemotherapy. Therefore, the design of a molecule that can target these pathways could be an effective strategy to reverse CRC progression and metastasis. In this study, twelve novel silybin derivatives, HM015a-HM015k (15a-15k) and compound 17, were screened for cytotoxicity in CRC cell lines.

HM015k, a Novel Silybin Derivative, Multi-Targets Metastatic Ovarian Cancer Cells and Is Safe in Zebrafish Toxicity Studies.

This study was designed to determine the mechanisms by which the novel silybin derivative, (E)-3-(3-(benzyloxy) phenyl)-1-(4-hydroxyphenyl)prop-2-en-1-one ( or ), produces its anticancer efficacy in ovarian cancer cells. Compound induced apoptosis in ovarian cancer cells in a time-dependent manner by significantly upregulating the expression of Bax and Bak and downregulating the expression of Bcl-2. Interestingly, induced the cleavage of Bax p21 into its more efficacious cleaved form, Bax p18.

A reappraisal of the 6-O-desmethylnaproxen-sulfating activity of the human cytosolic sulfotransferases.

In this study, we aimed to obtain a comprehensive account of the human cytosolic sulfotransferases (SULTs) that are capable of sulfating 6-O-desmethylnaproxen (O-DMN), a major metabolite of naproxen. Of the 13 known human SULTs tested, 7 (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C2, SULT1C4, and SULT1E1) displayed O-DMN-sulfating activity, when analyzed using an elevated substrate concentration (500 μmol·L) together with 14 μmol·L of the sulfate donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS). At 10 μmol·L O-DMN concentration, however, only SULT1A1 and SULT1A3 displayed detectable activity, with the former being nearly 2 orders of magnitude more active than the latter.