Chemomodulatory potential of Glycine max against murine skin and cervical papillomagenesis.
Singh M1, Mendez E, Rao AR, Kale RK.
Indian J Exp Biol. 2011 Nov;49(11):864-70
PMID: 22126018 [PubMed - indexed for MEDLINE]
In the present study, chemopreventive potential of Glycine max (G. Max) seeds was examined against DMBA-induced skin and MCA-induced cervical papillomagenesis in Swiss albino mice. Different doses (2.5, 5, and 7.5% w/w) of G. max were provided to animals in feed. Results exhibited a significant reduction in skin as well as cervical tumor incidence and tumor multiplicity (up to 75%) at all doses of test diet as compared to the control. Relatively, 7.5% test diet was most effective in protecting the animals against carcinogenesis. Further, detoxifying enzymes and antioxidative status was also evaluated in the liver of mice to understand the role of G. max in prevention of cancer. It was observed that the test diet containing G. max significantly elevated the specific activities of glutathione-S-transferase (GST), DT-diaphorase (DTD), superoxide dismutase (SOD), catalase (CAT), and glyoxalase I (Gly I). The test diet also elevated the content of reduced glutathione whereas it decreased the level of the peroxidative damage along with the specific activity of lactate dehydrogenase. It appeared that G. max seeds provided chemoprevention against skin and cervical papillomagenesis probably by modulating the detoxifying and antioxidative enzymes. It could be inferred that intake of G. max might help in reducing the risk of cancer.
Glycine soya diet synergistically enhances the suppressive effect of tamoxifen and inhibits tamoxifen-promoted hepatocarcinogenesis in 7,12-dimethylbenz[α]anthracene-induced rat mammary tumor model.
Mishra R1, Bhadauria S, Murthy PK, Murthy PS. Food Chem Toxicol. 2011 Feb;49(2):434-40. doi: 10.1016/j.fct.2010.11.020. Epub 2010 Nov 17. PMID: 21092749 [PubMed - indexed for MEDLINE
There is increasing interest in phytoestrogens as potential alternatives to synthetic selective estrogen receptor modulators (SERMs) in the prevention and therapy of breast cancer. The present study is aimed at determining whether dietary glycine soya (Glycine max seeds; GS), which is rich in phytoestrogens, can enhance the anti breast cancer efficacy of the SERM tamoxifen (TAM) and the effect of TAM and GS, either alone or in combination, on DMBA-initiated hepatocarcinogenesis in rat. For determination of enhancing effect, rats bearing palpable 7, 12-dimethylbenz[α] anthracene (DMBA)-induced mammary tumors were treated with TAM (10 mg kg(-1)/day) while being fed AIN-93G diet with or without added GS (3×10(4) mg kg(-1)), and the tumor growth was monitored up to 5 weeks of treatment. For determining the effect on hepatocarcinogenesis, DMBA-initiated rats were exposed to TAM and dietary GS as above for 6 weeks during promotion stage in a medium-term bioassay, and the development of placental form of glutathione-S-transferase (GST-P)-expressing preneoplastic liver lesions was quantified. Exposure to both TAM and dietary GS enhanced the anti tumor efficacy of TAM via a combination of tumor cell apoptosis (determined by TUNEL) and inhibition of tumor cell proliferation (determined by PCNA immunostaining) and suppressed the growth of GST-P-positive liver lesions. The findings show that dietary GS enhances the therapeutic efficacy of TAM against mammary tumors and minimizes TAM's hepatocarcinogenesis promotion potential.
Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis.
Hostanska K1, Nisslein T, Freudenstein J, Reichling J, Saller R.,
Breast Cancer Res Treat. 2004 Mar;84(2):151-60.
Hormone replacement therapy is contraindicated in women with breast cancer. Extracts from the rhizomes of Cimicifuga racemosa, have gained acceptance as a natural alternative for the treatment of menopausal symptoms. In the present study we investigated the antiproliferative activity of C. racemosa extracts (isopropanolic and ethanolic) on the estrogen receptor positive MCF-7 and estrogen receptor negative MDA-MB231 breast cancer cells by WST-1 assay. Down regulation of the proliferative activity and cell killing by isopropanolic and ethanolic extracts occurred in a clear dose-dependent response with a 50% growth inhibitory concentration of 54.1 +/- 11.4 and 80.6 +/- 17.7 micro g/ml in MCF-7 cells and of 29.5 +/- 3.0 and 58.6 +/- 12.6 microg/ml in MDA-MB231 cells, respectively. Further, the mode of cell death was identified as apoptosis by microscopic inspection and confirmed by light scatter characteristics and by detection of Annexin V adherence to phosphatidylserine by flow cytometry. In addition, the involvement of activated caspases was supported by the cleavage of cytokeratin 18 detected with M30 antibody. Increases in the level of M30-antigen of about 4-fold and 2-fold over untreated controls were observed in C. racemosa -treated MCF-7 and MDA-MB231 cells. These results indicate that C. racemosa extract exerts no proliferative activity, but kills the estrogen receptor positive MCF-7 as well as estrogen receptor negative MDA-MB231 cells by activation of caspases and induction of apoptosis.
Cimicifuga racemosa extract BNO 1055 inhibits proliferation of the human prostate cancer cell line LNCaP., Jarry H1, Thelen P, Christoffel V, Spengler B, Wuttke W.,
Phytomedicine. 2005 Mar;12(3):178-82.
Extracts from black cohosh (Cimicifuga racemosa, CR) exert an anti-proliferative action in human breast cancer cell cultures, which has been attributed to an anti-estrogenic effect. However, CR constituents do not bind to either of the known estrogen receptors. Thus, the anti-tumor effect of CR me be mediated by mechanisms not involving these receptors. Polycyclic aromatic hydrocarbons are toxic environmental pollutants, which indirectly act as anti-estrogens by activating the aryl hydrocarbon receptor (AhR). The AhR is widely expressed in mammalian tissues and tumors. A recent screening study demonstrated activation of the AhR by a variety of herbal extracts, among others, CR. Since activation of the AhR causes inhibition of growth of prostate cancer cells, we addressed the question, whether CR may not only inhibit growth of breast cancer--but also of prostate cancer cells. In the AhR ligand assay, the CR extract BNO 1055 reduced tracer binding to 71% of the control demonstrating interaction of constituents of this extract with the receptor. Under basal as well as under estradiol- and dihydrotestosterone stimulated conditions, the CR extract dose dependently inhibited proliferation of LNCaP cells. A significant reduction of cell growth was observed at a concentration as low as 50 ng/ml. Thus, it is demonstrated for the first time that CR compounds potently inhibit the growth of human prostate cancer cells in vitro. This anti-proliferative effect may be mediated via the AhR.
Antioxidant activity and anticancer effect of Vitex agnus-castus L. (Verbenaceae) seed extracts on MCF–7 breast cancer cells. Özlem Sultan Aslantürka and Tülay Aşkın Çelika. Caryologia: International Journal of Cytology, Cytosystematics and Cytogenetics Volume 66, Issue 3, 2013.
Aim: The aim of this study was to investigate the in vitro antioxidant and anticancer activities of diethyl ether, petroleum ether, ethyl acetate, methanol and water (infusion and decoction) extracts from Vitex agnus-castus L. (Verbenaceae) seeds.
Materials and methods: Antioxidant activities of crude extracts from V. agnus-castus L. seeds were evaluated by 1,1-diphenyl-2-picryl-hydrazyl radical (DPPH) scavenging assay, and anticancer activity of the extracts on MCF-7 breast cancer cells of extracts were evaluated by determining cytotoxic, DNA damaging and apoptotic activities with trypan blue exclusion assay, comet assay and Hoechst 33258/propidium iodide double staining.
Results: Although V. agnus-castus L. methanol and water (infusion and decoction) extracts showed significant DPPH scavenging activity, diethyl ether, petroleum ether and ethyl acetate extracts have low DPPH scavenging activity. However, all of the extracts showed a significant cytotoxic, DNA damaging and apoptotic effects in MCF-7 human breast cancer cells. Cytotoxic, DNA damaging and apoptotic activities of the extracts increased in concentration dependent manner.
Conclusion: Our results suggest crude extracts of V. agnus-castus seeds have potent antioxidant, cytotoxic and apoptotic activity. Further investigations are required for the isolation and identification of individual phenolic compounds in the extracts.
Anti-Cancer Effect of Angelica Sinensis on Women’s Reproductive Cancer. Hong-Hong Zhu, Guo-Hui Huang, Patricia L. Tate, Lyndon L. Larcom. Functional Foods in Health and Disease 2012, 2(6):242-250.
Objective: Danggui, the root of Angelica S inensis
, has traditionally been used for the treatment of women’s reproductive disorders in China for thousands of years. This study was to determine whether Danggui have potential anti-cancer effect on women’s cancer and its potential mechanism.
Methods: Danggui was extracted by ethanol.
The Cell Titer 96® Aqueous Non-Radioactive Cell Proliferation Assay was used to compare the effects of Danggui on human breast (MCF-7 and 7368) and cervical (CaSki and SiHa) cancer cells with its effects on normal fibroblasts (HTB-125).
A revised Ames test was used to test for antimutagenicity. The standard strains of Salmonellatyphimarium (TA) 100 and 102 were used in the test. Methyl methane sulfonate (MMS) and UV light were used as positive mutagen controls and ethanol and double distilled water (DDW) as controls. The SAS statistical software was used to analyze the data.
Results: Danggui was found to be much more toxic to all cancer cell lines tested than to normal fibroblasts. There was a significant negative dose-effect relationship between
Danggui and cancer cell viability. Average viability of MCF-7 was 69.5%, 18.4%, 5.7%, 5.7%, and 5.0% of control for Danggui doses 0.07, 0.14, 0.21, 0.32, and 0.64 ug/ul, respectively, with a Ptrend < 0.0001. Half maximal inhibitory dose (ID 50) of Danggui for cancer cell lines MCF-7, CaSki, SiHa and CRL-7368 was 0.10, 0.09, 0.10 and 0.07 ug/ul, Functional Foods in Health and Disease 2012, 2(6):242-250 Page 243 of 250 respectively. For the normal fibroblasts, ID 50 was 0.58 ug/ul. At a dose of 0.32 ug/ul, Danggui killed over 90% of the cells in each cancer cell line, but at the same dose, only 12.3% of the normal HTB-125 cells were killed. Revertants per plate of TA 100
decreased with the introduction of increasing doses of Danggui extracts with a Ptrend < 0.0001 when UV light was used as amutagen. There was no difference in revertants per plate between ethanol and DDW control groups.
Conclusions: Danggui could be used as a safe and effective adjuvant therapy to prevent and treat breast and cervical cancers. Anti-cancer effects may be due to its anti-mutagenicity. Danggui should be investigated as a potential adjuvant anti-cancer therapy for women’s cancer treatment and prevention of recurrence.
Curcumin-loaded γ-cyclodextrin liposomal nanoparticles as delivery vehicles for osteosarcoma. Dhule SS1, Penfornis P, Frazier T, Walker R, Feldman J, Tan G, He J, Alb A, John V, Pochampally R., Nanomedicine. 2012 May;8(4):440-51. doi: 10.1016/j.nano.2011.07.011. Epub 2011 Aug 10.
The delivery of curcumin, a broad-spectrum anticancer drug, has been explored in the form of liposomal nanoparticles to treat osteosarcoma (OS). Curcumin is water insoluble and an effective delivery route is through encapsulation in cyclodextrins followed by a second encapsulation in liposomes. Liposomal curcumin's potential was evaluated against cancer models of mesenchymal (OS) and epithelial origin (breast cancer). The resulting 2-Hydroxypropyl-γ-cyclodextrin/curcumin - liposome complex shows promising anticancer potential both in vitro and in vivo against KHOS OS cell line and MCF-7 breast cancer cell line. An interesting aspect is that liposomal curcumin initiates the caspase cascade that leads to apoptotic cell death in vitro in comparison with DMSO-curcumin induced autophagic cell death. In addition, the efficiency of the liposomal curcumin formulation was confirmed in vivo using a xenograft OS model. Curcumin-loaded γ-cyclodextrin liposomes indicate significant potential as delivery vehicles for the treatment of cancers of different tissue origin.
FROM THE CLINICAL EDITOR:
Curcumin-loaded γ-cyclodextrin liposomes were demonstrated in vitro to have significant potential as delivery vehicles for the treatment of cancers of mesenchymal and epithelial origin. Differences between mechanisms of cell death were also evaluated.
Older Biogenistein Citations
Inhibitory effect of genistein on bone resorption in tissue culture. Biochemical Pharmacol 1998,55 (1),71-76.
a) Genistein inhibits the growth of human-patient BPH and prostate cancer in histoculture. Prostate 1998, 34(2), 75-79.
b) Inhibition of human prostate cancer cell proliferation by genistein. Proceed Am Assoc Cancer Res 1997, 38, 262.
c) Genistein inhibits proliferation and in vitro invasive potential of human prostatic cancer cell lines. Anticancer Res 1997, 17, (2A).
a) Rationale for the use of genistein-containing soy matrixes in chemo-prevention trials for breast cancer cells. J Cell Biochem.
b) The evidence for soybean products as cancer preventive agents. J Nutr 1995, 125 (3 Suppl), 733S-743 S.
c) Growth-inhibitory effects of the natural phytoestrogen genistein in MCF-7 human breast cancer cells. European J cancer 1994, 1675-1682
d) Estrogenic and antiproliferative properties of genistein and other flavonoids in human breast cancer cells in vitro. Nutr Cancer.
a) Genistein, the dietary-derived angiogenesis inhibitor, prevents LDL oxidation and protects endothelial cells from damage by atherogenic LDL. Thrombosis and Vascular Biology 1997, 17(11), 2868-2874.
b) Role of dietary phyto-oestrogens in the protection against cancer and heart disease. Biochem Soc Trans. 1996, 24(3), 795-800