Anti‐inflammatory and Anticarcinogenic Effect of Genistein Alone or in Combination with Capsaicin in TPA‐Treated Rat Mammary Glands or Mammary Cancer Cell Line

Abstract

The topical application of TPA (12-O-tetradecanoylphorbol-13-acetate) to animal skin or direct treatment of TPA to cell cultures leads to inflammatory responses by enhancing cyclooxygenase 2 (COX-2) expression, and specific COX-2 inhibitors counteract this kind of inflammatory response. Furthermore, suppression of these inflammatory events by dietary-origin chemopreventive agents can provide a potential strategy to control carcinogenesis. In this in vivo study, the mammary glands of mature female rats were treated with TPA, and then the effects of genistein alone or in combination with capsaicin on suppression of inflammatory responses were examined. The combined effects of genistein and capsaicin on COX-2, pJNK, pERK, and pp38 expressions were additive or nonadditive, depending on signals tested. In vitro MCF-7 breast cancer cells, the apoptotic bodies as shown with Hoechst 33342 dye, exhibited a synergistic effect between genistein and capsaicin. The abilities of genistein alone or in combination with capsaicin in inhibiting breast cancer cell proliferation through the modulation of AMPK and COX-2 were tested. AMPK activation by genistein in combination with capsaicin is critical for inhibiting COX-2. We propose that genistein in combination with capsaicin exerts anti-inflammatory and anticarcinogenic properties through the modulation of AMPK and COX-2 and possibly various mitogen-activated protein kinases synergistically or nonsynergistically.

Sulforaphane Inhibits Growth of Human Breast Cancer Cells and Augments the Therapeutic Index of the Chemotherapeutic Drug, Gemcitabine

“…The untreated MCF-7cells showed a high level of expression of COX-2 while on SFN treatment it was found to be significantly downregulated in MCF-7 cells in a time dependant manner (Figure 6). Several dietary components including curcumin, green tea catechins, genistein etc have been shown to suppress COX-2 expression (Plummer et al, 1999;Gerhäuser et al, 2003;Hwang et al, 2009). Hence, it can be inferred that reduction in COX-2 expression may be an important target for chemoprevention by agents like SFN.…”

The role of AMP-activated protein kinase in quercetin-induced apoptosis of HL-60 cells

“…Park et al [23] found that catechin, another plant flavonoid, could induce the apoptosis of colon cancer cells by activating the AMPK/Cox-2 pathway in a low-dose H 2 O 2 condition. Hwang et al [24] showed that genistein could inhibit the proliferation of tumor cells by activating AMPK and further affecting Cox-2. Quercetin expresses its anti-tumor function by a complicated mechanism.…”

Chemoprevention and Novel Treatments of Non-Muscle Invasive Bladder Cancer

“…One study showed genistein inhibited EGF-R and EGF, of which the quantity and distribution are associated with urothelial abnormalities (Theodorescu et al, 1998). Another study on genistein showed that it might down regulate COX-2 (Hwang et al, 2009), which has been shown to play a role in tumorigenesis. A 2006 study indicated genistein down regulates nuclear factor kappa-B in bladder tumor tissue and reduces circulating insulin-like growth factor-1 levels, both important in tumor metastasis .…”