In vitro effects on proliferation, apoptosis and colony inhibition in ER-dependent and ER-independent human breast cancer cells by selected mushroom species

Abstract

Breast cancer is the most commonly diagnosed cancer among women in Western countries. Currently, there is no effective therapy for malignant estrogen-independent breast cancer. We have screened 38 species of edible mushroom on human estrogen-receptor positive (MCF-7) and estrogenreceptor negative (MDA-MB-231, BT-20) breast cancer cells to select potential agents with broad-spectrum antitumor activity against breast cancer cells. Water-based extracts of three mushroom species, Coprinellus sp., Coprinus comatus, Flammulina velutipes (CME, CCE and FVE respectively), were identified as novel anti-breast cancer agents. The antitumor activities include: 1) marked growth inhibition of both ER + and ERbreast cancer cells; 2) induction of rapid apoptosis on both ER + and ERcells; 3) significant inhibition of MCF-7 tumor colony formation in vitro. The antiproliferative and cytotoxic activities of the three mushroom extracts were dose-dependent, regardless of the hormone receptor status of the cancer cells. The degree of produced cytotoxicity on ERbreast cancer cells was very high, while the IC 50 of mushroom extract CME was found to be as low as 40 μg/ml on MDA-MB-231 cells and the IC 50 of mushroom extract FVE was only 30 μg/ml on BT-20 cells. More interestingly, mushroom extracts CME and FVE induced an exceptionally rapid apoptosis on MCF-7 and MDA-MB-231 detected by Annexin V-FITC within 2 h of treatment and DNA fragment endlabeling assay (TUNEL) in 5 h of treatment. Anchorageindependent growth assays indicated that the MCF-7 tumor colony formation rate was reduced by 60% in CCE-and CME-treated cells and nearly completely inhibited (99%) by FVE treatment. These results suggest that mushroom species Coprinus comatus, Coprinellus sp. and Flammulina velutipes contain potent antitumor compounds for breast cancer. Our finding is important due to the lack of chemotherapeutic and chemopreventive agents for ERhuman breast cancer.

Dietary Mushroom Intake and the Risk of Breast Cancer Based on Hormone Receptor Status

“…Such polysaccharides have been hypothesized as plausible biological links to the mechanisms by which mushrooms function on macrophages, natural killer cells, and subsets of T cells. In vitro effects of selected mushroom species have been reported on proliferation, apoptosis, colony inhibition, and aromatase activity (8)(9)(10)(11)(12)(13). Only two epidemiological studies, one on gastric cancer (35) and the other on breast cancer, have focused on the effect of dietary mushrooms (14).…”

“…The potentially antitumor effects of mushroom extracts and constituents include blocking the formation of carcinogens, suppressing DNA synthesis, enhancing cell differentiation, and competing with estrogen for estrogen receptors (7). Most research has entailed isolating pharmaceutically active mushroom compounds, and these compounds have been hypothesized as plausible biological links to the mechanisms by which mushrooms function on macrophages, natural killer cells, and subsets of T cells (8)(9)(10)(11)(12)(13). Although antitumor activities have been reported, very few studies have investigated the association between mushrooms and breast cancer as defined by hormone receptor status.…”

Antibacterial and cytotoxic activity from basidiocarp extracts of the edible mushroom Lactarius indigo (Schw.) Fr. (Russulaceae)

“…These results contrast with reports for other species of Basidiomycota, although at significantly higher concentrations of aqueous extract than those used in the present study. For example, the aqueous extracts of Coprinellus sp., Flammulina velutipes and Coprinus comatus were capable of inhibi-ting the proliferation in vitro of MCF7 cells, with IC 50 values of 120, 150 and 450 µg/ml, respectively (Gu and Leonard, 2006). Consequently, we cannot discard the possibility that the aqueous extract of L. indigo may present antiproliferative activity against the other cell lines evaluated in the present work at higher concentrations than those used by us, a possibility that needs to be evaluated in future works.…”

The role of edible mushrooms in health: Evaluation of the evidence

“…However, an in vitro study using water-based extracts of Coprinellus sp., Coprinus comatus, Flammulina velutipes, significantly inhibited growth of both estrogen-receptor positive (ER+) and estrogen-receptor negative (ERÀ) breast cancer cells, induction of rapid apoptosis on both ER+ and ERÀ cells, and significantly inhibited MCF-7 tumor colony formation in vitro. These activities were dose-dependent, regardless of Isai et al (2009) the hormone receptor status of the cancer cells (Gu & Leonard, 2006). Higher dietary intake of mushrooms decreased breast cancer risk in both pre-and post-menopausal women and an additional decreased risk of breast cancer was observed from a synergistic effect of mushrooms and green tea in a casecontrolled study (Zhang, Huang, Xie, & Holman, 2009).…”