Background: Epigallocatechin-3-gallate (EGCG), one of the major catechins in green tea, is a potential chemopreventive agent for various cancers. The aim of this study was to examine the effect of EGCG on the expression of heat shock proteins (HSPs) and tumor suppression. Methods: Cell colony formation was evaluated by a soft agar assay. Transcriptional activity of HSP70 and HSP90 was determined by luciferase reporter assay. An EGCG-HSPs complex was prepared using EGCG attached to the cyanogen bromide (CNBr)-activated Sepharose 4B. In vivo effect of EGCG on tumor growth was examined in a xenograft model. Results: Treatment with EGCG decreased cell proliferation and colony formation of MCF-7 human breast cancer cells. EGCG specifically inhibited the expression of HSP70 and HSP90 by inhibiting the promoter activity of HSP70 and HSP90. Pretreatment with EGCG increased the stress sensitivity of MCF-7 cells upon heat shock (44°C for 1 h) or oxidative stress (H₂O₂, 500 μM for 24 h). Moreover, treatment with EGCG (10 mg/kg) in a xenograft model resulted in delayed tumor incidence and reduced tumor size, as well as the inhibition of HSP70 and HSP90 expression. Conclusions: Overall, these findings demonstrate that HSP70 and HSP90 are potent molecular targets of EGCG and suggest EGCG as a drug candidate for the treatment of human cancer.

Oxidative stress and inflammation play critical roles in the development of cardiovascular diseases. Cinnamaldehyde (CA) is a natural compound from Cinnamomum cassia, and its anticancer, antimicrobial and anti‑inflammatory activities have been widely investigated. In the present study, the cytoprotective and anti‑inflammatory effects of CA on H2O2‑ or tumor necrosis factor (TNF)‑α‑exposed human umbilical vein endothelial cells (HUVECs) were examined. CA and its natural derivative, 2‑methoxycinnamaldehyde (MCA), markedly increased the cellular protein level of heme oxygenase‑1 (HO‑1) and promoted the translocation of nuclear factor erythroid 2‑related factor 2 (Nrf2) to the nucleus. CA‑mediated Nrf2/HO‑1 activation protected the HUVECs from H2O2‑induced oxidative stress, which promotes apoptosis. HO‑1 depletion by siRNA attenuated the CA‑mediated cell protective effects against oxidative stress. Additionally, CA markedly inhibited the adhesion of U937 monocytic cells to HUVECs by decreasing the expression level of vascular cell adhesion protein 1 (VCAM‑1). An in vivo experiment confirmed the anti‑inflammatory effects of CA, as lipopolysaccharide (LPS)‑induced inflammatory cell infiltration was effectively inhibited by the compound. Overall, these observations suggest that CA may be used as a therapeutic agent for oxidative stress‑mediated cardiovascular diseases, such as atherosclerosis.

Considering the high metastatic potential of colorectal cancer (CRC), the inhibition of metastasis is important for anti-CRC therapy. Agrimonia pilosa Ledeb (A. pilosa) is a perennial herbaceous plant that is widely distributed in Asia. The extracts of A. pilosa have shown diverse pharmacological properties, such as antimicrobial, anti-inflammatory, and antitumor activities. In the present study, the antimetastatic activity of A. pilosa was evaluated. Methanol extraction from the roots of A. pilosa was performed by high-performance liquid chromatography (HPLC) and 12 fractions were obtained. Among these, fraction 4 showed the most potent inhibitory effect on the migration of colon cancer cells. Using LC-HR MS analysis, quercetin and quercitrin were identified as flavonoids contained in fraction 4. Like fraction 4, quercetin and quercitrin effectively inhibited the migration and invasion of RKO cells. While the level of E-cadherin was increased, the levels of N-cadherin and vimentin were decreased by the same agents. Although they all activate the p38, JNK, and ERK signaling pathways, only SP600125, an inhibitor of the JNK pathway, specifically inhibited the effect of fraction 4, quercetin, and quercitrin on cell migration. An in vivo experiment also confirmed the antitumor activity of quercetin and quercitrin. Collectively, these results suggest that A. pilosa and its two flavonoids, quercetin and quercitrin, are candidates for the antimetastatic treatment of CRC.

Cinnamaldehyde has been shown to effectively induce apoptosis in a number of human cancer cells. In the present study, cinnamaldehyde derivative-induced apoptosis and its signaling pathways were assessed in p53-wild (SGT) and p53-mutant (YD-10B) human head and neck cancer cells. The cinnamaldehyde derivatives, 2'-hydroxycinnamaldehyde (HCA) and 2'-benzoyloxycinnamaldehyde (BCA), exhibited powerful anti-proliferative effects on SGT and YD-10B cells. The apoptotic effect induced by HCA or BCA was supported by caspase-3, -7, -9 and PARP activation, and confirmed by Annexin V-FITC/PI double staining. HCA induced the expression of p21 in both SGT and YD-10B cells. Furthermore, HCA induced the level of pro-apoptotic Bak1 expression while decreasing the level of anti-apoptotic Bcl-2 in both cell lines, suggesting that HCA induced the cell death pathway in a p53-independent manner. HCA also induced the expression of LC3B in SGT and YD-10B cells. Following pre-incubation with the autophagy inhibitor 3-MA, HCA-induced apoptosis was largely increased in SGT cells, while inhibited in YD-10B cells, suggesting that autophagy may actively contribute to HCA-induced apoptosis. Taken together, these observations suggest that HCA may be an effective therapeutic agent in the treatment of head and neck cancer regardless of p53 status.