Clinical characteristics of colorectal cancer patients and anti-neoplasm activity of genistein

Abstract

Background: Epidemiologically, the disease incidence of colorectal cancer (CRC) ranks the third among all malignant tumors, and its mortality is the second following lung cancer. If unmanaged, CRC will develop fatal invasiveness and metastasis. However, existing chemotherapy is limitedly effective to treat metastatic CRC. Genistein, a functional phytoestrogen, is found with potent pharmacological activity against cancer cells. Therefore, this study was designed to characterize the clinical signatures of human CRC and to conduct anti-CRC experiments using genistein.

Methods: Briefly, the plasma, tumor, non-tumor samples of CRC patients were harvested for biological experiments, followed by analysis of clinical data. A pharmacological study in vitro of genistein for treating CRC cells was conducted accordingly.

Results: In diagnostic data, molecular tumor biomarkers in CRC patients were detected in plasma samples, consistent with pathological and imaging diagnoses of CRC. Notably, carcinomatous expressions of miR-95, serum glucocorticoid kinase 1 (SGK1), B-cell lymphoma-2 (Bcl-2), extracellular regulated protein kinase 1 (Erk1) in human CRC were notably elevated when compared to those in non-tumor controls. In pharmacological experiments using cell culture model, genistein-treated CRC cells resulted in reduced cellular viability, elevated lactate dehydrogenase (LDH) content, increased apoptotic cells and TdT mediated dUTP nick end labeling (TUNEL)-positive cells following a dose-dependent manner. Interestingly, down-regulated expressions of endogenous miR-95, SGK1, Bcl-2, Erk1 were observed after genistein treatments in a dose-dependent way.

Conclusions: Collectively, the current clinical data indicate pathological markers of miR-95, SGK1, Erk1 in human CRC cases, and further experimental findings reveal that anti-CRC pharmacological mechanism using genistein was implicated in suppression of cellular miR-95, SGK1, Erk1 expressions. Together, genistein may be a promising bioactive compound for treating CRC.

Keywords: Biological targets; Colorectal cancer; Genistein; Mechanism.