Veronika Slivova

Ganoderma lucidum suppresses motility of highly invasive breast and prostate cancer cells

A dried powder from basidiomycetous fungi, Ganoderma lucidum, has been used in East Asia in therapies for several different diseases, including cancer. However, the molecular mechanisms involved in the biological actions of Ganoderma are not well understood. We have recently demonstrated that phosphatidylinositol 3-kinase (PI 3-kinase) and nuclear factor-kappaB (NF-kappaB) regulate motility of highly invasive human breast cancer cells by the secretion of urokinase-type plasminogen activator (uPA). In this study, we investigated the effect of G. lucidum on highly invasive breast and prostate cancer cells. Here we show that spores or dried fruiting body of G. lucidum inhibit constitutively active transcription factors AP-1 and NF-kappaB in breast MDA-MB-231 and prostate PC-3 cancer cells. Furthermore, Ganoderma inhibition of expression of uPA and uPA receptor (uPAR), as well secretion of uPA, resulted in the suppression of the migration of MDA-MB-231 and PC-3 cells. Our data suggest that spores and unpurified fruiting body of G. lucidum inhibit invasion of breast and prostate cancer cells by a common mechanism and could have potential therapeutic use for cancer treatment.

Cellular and physiological effects of soy flavonoids.

Recent experimental and epidemiological studies have provided convincing evidence for a variety of health benefits derived from the consumption of soy and soy food products. For example, soy isoflavones are felt to protect against different cancers, cardiovascular disease, and bone loss. Many studies have demonstrated the effect of soy isoflavones on specific target molecules and signaling pathways, including but not limited to, cell proliferation and differentiation, cell cycle regulation, apoptosis, angiogenesis, cell adhesion and migration, metastasis, and activity of different enzymes. Isoflavones also share structural homologies with estrogens and are therefore classified as phytoestrogens with weak estrogenic properties. Since isoflavones bind to estrogen receptors (ER alpha and ER beta), they are considered to be possible estrogen receptor modulators. However, isoflavones can also exert biological effects independent of their phytoestrogenic activities. Recent studies suggest beneficial health effects of soy and recommend increasing the intake of isoflavone-rich soy protein to the level of intake commonly used in Asian countries.

Green tea polyphenols modulate secretion of urokinase plasminogen activator (uPA) and inhibit invasive behavior of breast cancer cells.

Many epidemiological studies have suggested that consumption of green tea may decrease the risk of cancer. The chemopreventive effect of green tea polyphenols (GTP) has been demonstrated through the inhibition of cell proliferation and angiogenesis in cell culture and animal models of breast cancer. Metastasis of breast cancer is the major reason for the high mortality of breast cancer patients and is directly linked to the invasive behavior of breast cancer cells. Cancer metastasis consists of several interdependent processes including cancer cell adhesion, cancer cell migration, and invasion of cancer cells. In this study, we evaluated the effect of GTP on human breast cancer cells, and we show that in addition to inhibiting cell growth, GTP also suppressed the invasive behavior of MDA-MB-231 cells. These anti-invasive effects of GTP were the result of the inhibition of constitutively active transcription factors AP-1 and NF-κB, which further suppressed secretion of urokinase plasminogen activator (uPA) from breast cancer cells. Based on these results, it can be hypothesized that GTP treatment resulted in the inhibition of formation of signaling complexes responsible for cell adhesion and migration (uPA, uPA receptor, vitronectin, integrin receptor) and cell invasion (uPA, uPA receptor). Our results indicate that GTP may contribute to the anticancer effects of green tea by inhibiting the invasive behavior of cancer cells.

Biologic Activity of Spores and Dried Powder from Ganoderma lucidum for the Inhibition of Highly Invasive Human Breast and Prostate Cancer Cells

OBJECTIVE Ganoderma lucidum has been used in East Asia as a home remedy to prevent or cure cancer. Furthermore, Ganoderma lucidum is one of the herbs in the herbal mixture PC-SPES that has become an alternative herbal therapy for prostate cancer. Because the dried powder of ganoderma is commercially available as a dietary supplement itself, the purpose of this study was to evaluate the biologic activity of samples of Ganoderma lucidum from different sources. METHODS Samples of Ganoderma lucidum were characterized morphologically and evaluated for their ability to inhibit cell migration of highly invasive breast cancer MDA-MB-231 cells and prostate cancer PC-3 cells. Because the inhibition of cell motility is directly linked to the inhibition of the signaling pathway for constitutively active NF-kappaB in breast and prostate cancer cells, we determined how different samples of Ganoderma lucidum inhibit constitutively active NF-kappaB in a reporter gene assay. RESULTS Some of the samples of Ganoderma lucidum demonstrated strong inhibition of cancer cell migration comparable to the inhibition of constitutively active NF-kappaB, whereas other samples showed less or no activity in highly invasive estrogen receptor-negative breast cancer cells or androgen receptor-negative prostate cancer cells, respectively. Interestingly, we did not find any correlation between the purity and composition (spores versus powder) of Ganoderma lucidum and biologic activity. CONCLUSIONS Ganoderma lucidum has demonstrated strong activity against breast and prostate cancer cells. Nevertheless, the composition of samples did not correlate with their ability to inhibit cell migration and activation of NF-kappaB in vitro.

Gossypol inhibits growth, invasiveness, and angiogenesis in human prostate cancer cells by modulating NF-κB/AP-1 dependent- and independent-signaling.

Although previous studies demonstrated anticancer activities of gossypol through the induction of apoptosis, the molecular mechanism(s) responsible for the inhibitory effects of gossypol on the metastatic behavior of cancer cells remain to be elucidated. Here, we show that gossypol inhibits growth of human prostate cancer cells through the modulation of cell cycle regulatory proteins. We also demonstrate that gossypol inhibits invasive behaviors (adhesion, migration, and invasion) and angiogenesis. These effects are mediated by the suppression of AP-1 and NF-κB activity, resulting in the inhibition of secretion of urokinase plasminogen activator and vascular endothelial growth factor, and the down-regulation of expression of chemokine receptor 4 in PC3 cells. In summary, our data suggest that gossypol could have potential therapeutic effect for the treatment of invasive prostate cancer.