HOXA7 Promotes Metastasis in KRAS Mutant Colorectal Cancer by Regulating Myeloid-derived Suppressor Cells

Background: KRAS mutation accounts for 30-50% of human colorectal cancer (CRC). Due to paucity of effective treatment options, KRAS mutant CRC is difficult to treat in clinic. Metastasis is still the major reason for the high mortality of KRAS mutant CRC, but the exact mechanism remains unclear. Here, we report a novel role of Homeobox 7 (HOXA7) in promoting KRAS mutant CRC metastasis and probed therapy strategies for these subpopulation patients.Methods: The expression of HOXA7 was detected in human CRC cohort by immunohistochemistry. The function of HOXA7 in KRAS mutant CRC metastasis was analyzed by cecum orthotopic model. Results: The elevated expression of HOXA7 was positively correlated with lymph node metastasis, distant metastasis, poorer tumor differentiation, higher TNM stage, and poor prognosis in CRC patients. Furthermore, HOXA7 is an independent prognostic marker of KRAS mutant CRC patients (P<0.001), while not for KRAS wild-type CRC patients (P=0.575). HOXA7 overexpression increased the metastasis ability of KRAS mutant CT26 cell, and promoted the infiltration of MDSCs at the same time. When MDSCs infiltration was depleted by CXCR2 inhibitor, it can markedly suppress the metastasis rate in CT26 cell. The combination of CXCR2 inhibitor SB265610 and anti-programmed death-ligand 1 (anti-PD-L1) can largely inhibit metastasis in KRAS mutant CRC. Conclusions: HOXA7 overexpression upregulated CXCL1, which promoted MDSCs infiltration. Interruption of this loop might provide a promising treatment strategy for HOXA7-mediated KRAS mutant CRC metastasis.

Relationship between copper(ii) complexes with FomA adhesin fragments ofF. nucleatumand colorectal cancer. Coordination pattern and ability to promote ROS production

The copper(ii) binding of the fragments of FomA was studied. Complexes stimulate the CT26 cell line to produce ROS which lead to oxidative stress.

Cytotoxic Compounds from Aerial Organs of Xanthium Strumarium

Xanthium strumarium L., the main species of the genus Xanthium, is ubiquitously distributed. The aim of this study was to determine the cytotoxic effect of aerial organs of X. strumarium, grown in Cuba, against cancer cell lines and the isolation of compounds potentially responsible for this activity. Initially, an ethanol partitioning procedure yielded the XSE extract that was subsequently fractionated with chloroform resulting in a XSCF fraction. Both, XSE and XSCF fractions exhibited cytotoxic effects on MDA MB-231, MCF7, A549 and CT26 cell lines by using the MTT assay. Above all, the XSCF fraction was more active than XSE. For this reason, XSCF was subsequently fractionated by silica gel chromatography and the active fractions submitted to semi-preparative HPLC for isolation of bioactive compounds. Six sub-fractions (SF1 to SF6) were recovered. Sub-fractions 3 and 6 were the most active on each assayed cell line, while sub-fractions 4 and 5 were only active against A549 and CT26 cell lines. In each case, sub-fraction 6 showed the strongest inhibitory effect. The HPLC-DAD fingerprint of sub-fraction 6 showed a single peak that was identified by GC-MS as (-) spathulenol, a sesquiterpene with reported antitumor activity.