A novel complex, [Cu(acetylethTSC)Cl]Cl•0.25C2H5OH 1 (where acetylethTSC = (E)-N-ethyl-2-[1-(thiazol-2-yl)ethylidene]hydrazinecarbothioamide), was shown to have anti-proliferative activity against various colon and aggressive breast cancer cell lines. In vitro studies showed that complex 1 acted as a poison inhibitor of human topoisomerase IIα, which may account for the observed anti-cancer effects.

Fungal metabolites continue to show promise as a viable class of anticancer agents. In the present study, we investigated the efficacy of the fungal metabolite, fusarochromanone (FC101), for its antitumor activities in glioblastomas, which have a median survival of less than two years and a poor clinical response to surgical resection, radiation therapy and chemotherapy. Using clinically applicable doses, we demonstrated that FC101 induced glioblastoma apoptotic cell death via caspase dependent signaling, as indicated by the cleavage of poly(ADP-ribose) polymerase, glioblastoma (PARP). FC101 also induced differential reactive oxygen species (ROS) levels in glioblastoma cells, contrasting a defined role of oxidative stress in apoptotic cell death observed with other fungal metabolites. Furthermore, the antitumorigenic effects of FC101 on tumor cell migration were assessed. Cell migration assays revealed that FC101 significantly reduced the migratory capacity of glioblastomas, which are incredibly invasive tumors. Taken together, the present study establishes FC101 as a candidate anticancer agent for the cooperative treatment of glioblastomas.

Rosehips are blossoms from the wild rose (Rosa canina) and are commonly used as an herbal remedy. Previous reports have shown that extracts made from rosehip plants are able to reduce cell proliferation of cancer cells. In this study, we investigated the efficacy of rosehip extracts in preventing cell proliferation of three human glioblastoma cell lines A-172, U-251 MG and U-1242 MG cell lines. Each of the glioblastoma cell lines treated with rosehip extracts (1 mg/mL -25 ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when inhibitors of the MAPK (U0126, 10 µM) or AKT (LY294002, 20 µM) signaling pathways were utilized. Additionally, pretreatment of the these cell lines with Rosehip extracts (1 mg/mL -25 ng/mL) selectively decreased AKT, MAPK, and p70S6K phosphorylation suggesting these extracts prevent glioblastoma multiforme cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from colorimetric cell death assays, cell cycle analysis by flow cytometry, as well as western blot studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Moreover, rosehip extracts were able to increase the efficacy of Temozolomide, a chemotherapeutic agent used to treat patients with glioblastomas. Surprisingly, rosehip extracts demonstrated a greater inhibition of cell proliferation than in combination with Temozolomide (100 µM) or Temozolomide as a single agent. Taken together these data suggest that rosehip extracts are capable of decreasing glioblastoma cell proliferation without promoting apoptosis and demonstrate a greater cell proliferation inhibitory effect than Temozolomide. More importantly, rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for glioblastomas.

Abstract((E)-2-(2-hydroxybenzylideneamino)phenolato-2,2-diphenyl-6-aza-1,3-dioxa-2-stanna- [d,h] dibenzocyclononene, [Sn(Ph 2 SB)] (compound 1, where Ph 2 SB=(E)-2-(2-hydroxybenzylideneamino)phenolato Schiff base) and two novel compounds, [[SnPh 2 (F-azoSB)] (compound 2, where F-azoSB=4-((E)-(4-fluorophenyl) diazenyl)-2-((E)-(2-hydroxyphenylimino)methyl)phenolato Schiff base), [[SnPh 2 (sulf-azoSB)]0.125CHCl 3 (compound 3, where sulfamerazineazosalSB=4-((E)-(4-hydroxy-3-((E)-(2-hydroxyphenylimino)methyl)phenyl)diazenyl)-N-(4-methylpyrimidin-2-yl) benzenesulfonamide Schiff base), and the control compound, cisplatin (compound 4) were analysed to comparatively determine their effect on cancer cell growth. Anti-cancer properties of compounds 1-4 were examined using glioblastoma (U-1242 MG), colorectal (HT-29 and HCT-116), and skin (A431) human cancer cell lines. With regards to human glioblastoma cells, compounds 1 and 3 demonstrated anti-proliferative capacity in the cell line tested. Specifically, compounds 1 and 3 inhibited cell proliferation by 50% at concentrations between 10 and 50 µM. With respect to colon cancer cell lines, the IC 50 values for compounds 1-3 ranged from 3.04 ± 0.98 to 104.51 ± 13.87 µM. In the case of HCT-116, this translates to a 3-to 73-fold inhibitory effect of compounds 1-3 over cisplatin. In all cell lines tested, the chemo-effect was more pronounced with compounds 1-3 than with the control (compound 4); demonstrating that these azo-containing Sn(IV) complexes were more potent than compound 4. The overall effect of compounds 1-3 in the induction of appotosis and the inhibition of proliferation have defined an essential role for these compounds in chemotherapy. IntroductionFrom the late 1960s until the present, there have been significant advances in both the early detection and the treatments of cancer. Despite these advances overall incidences of cancer and deaths from cancer have increased during the same period [1]. These counterintuitive increases have been the impetus for development of new drugs for cancer treatment. In this context the organometallic compounds have been widely investigated as potential anti-tumour agents. Metallocene dihalide complexes Cp 2 MX 2 (where M=titanium, vanadium, niobium, or molybdenum) were the first early transition metal complexes that were shown to have anti-tumour activity. In addition, the organometallic-DNA and organometallic-nucleic acid interactions of these compounds have also been investigated [2][3][4]. More recently, ferricenium salts, organotin, and bismuth complexes have also emerged as examples of organometallic compounds that have been found to exhibit interesting anti-tumour activity [5].The biological activity of organotin compounds has become well known due to their practical applications as fungicides, bactericides, biocides, and pesticides [3,[6][7][8]. It is now well established that organotin compounds are very important in cancer chemotherapy [9] and as potential anti-cancer agents [10][11][12][13]. This is due in part to thei...

Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, characterized by its lack of the human epidermal growth factor receptor-2 (HER-2), the estrogen receptor (ER), and the progesterone receptor (PR). The high prevalence of triple negative tumors in young women is more commonly observed in young African American (AA) women. Currently, the existing targeted therapy is of minimal benefit in TNBCs. Akt and MAPK have been shown to promote cell proliferation in triple negative breast cancer and MAPK expression may be an underlying mechanism contributing to the generation of chemo-resistance in triple-negative breast cancer. Due to major concerns involving the occurrence of side effects and the emergence of drug-resistant cancer cells, there has been growing interest in the use of naturally occurring molecules with chemo-preventive and chemo- therapeutic properties in cancer treatment. Rosehip extracts have been used as dietary supplements to relieve symptoms associated with diarrhea, gastritis, and rheumatoid arthritis and have been shown to prevent cell proliferation in glioblastomas. This study investigated the efficacy of rosehip extracts in preventing cell proliferation in African American triple negative (HCC70, HCC1806) and luminal (HCC1500) breast cancer cell lines. Each of the breast cancer cell lines were treated with rosehip extracts (1mg/mL -25ng/mL) demonstrated a significant decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to or better than the decrease of cell proliferation observed when known inhibitors of the MAPK (U0126, 10 μM) or AKT (LY294002, 20 μM) signaling pathways were utilized. Additionally, pretreatment of these cell lines with these Rosehip extracts (1mg/mL -25ng/mL) selectively decreased AKT, MAPK, p70S6K, and S6 phosphorylation suggesting these extracts prevent AA TNBC cell proliferation by blocking both the MAPK and AKT signaling mechanisms. Results from cell cycle analysis by flow cytometry, western blot analysis, as well as apoptosis studies demonstrate that rosehip extracts inhibit cell proliferation but do not promote apoptosis. Rosehip extracts also have a synergistic effect with Doxorubicin (20µM), a chemotherapeutic agent used to treat patients with breast cancer, in preventing triple negative breast cancer cell proliferation. Taken together these data suggest that rosehip extracts are capable of decreasing cell proliferation in African American triple negative breast cancer cells without promoting apoptosis and demonstrate a synergistic inhibition of cell proliferation with Doxorubicin, and rosehip extracts may serve as an alternative or compliment to current chemotherapeutic regimens for triple negative breast cancer. Citation Format: Patrice Cagle, Tonisha Coburn, Patrick M. Martin. Rosehip (Rosa canina) extracts prevent MAPK and AKT-mediated cell proliferation in African American triple-negative breast cancer cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3213. doi:10.1158/1538-7445.AM2014-3213

Triple Negative Breast Cancer (TNBC) is an aggressive form of breast cancer, characterized by its lack of the human epidermal growth factor receptor-2 (HER-2), the estrogen receptor (ER), and the progesterone receptor (PR). Due to the lack of these hormone receptors, TNBC has abnormal therapeutic results; leading to the need for unique treatment methods. TNBC has a partial response to chemotherapy, which is associated with the lack of clinically established targeted therapies. Plant extracts have shown to be useful as chemopreventive agents due to their disruption of pro-survival and proliferative mechanisms on cancer cells. Rosehip extracts have shown potential anti-proliferative activity against cancer cells in vitro. This study investigated the effect of rosehip extracts in TNBC cell lines (HCC1806 and MB157) and basal-like breast cancer cell lines (HCC70 and HCC1500). To determine the inhibitory role of rosehip extracts in cell proliferation, MTT assays were conducted, following treatment with varying concentrations of rosehip extracts (1mg/ml, 250ug/ml, 25ug/ml, and 25ng/ml) for 48 hours. The data suggests that rosehip extracts, can significantly decrease cell proliferation in all the breast cancer cell lines assayed. Preliminary studies suggest that this is accomplished without toxic effects. Western blot analysis was used to investigate which signaling pathway rosehip extracts were affecting. Western Blot analysis suggests that rosehip extracts are inhibiting p70 S6 kinase phosphorylation and its ability to act as a kinase for S6 ribosomal protein. Based on these findings, rosehip extracts prevent cell proliferation by interfering with the p70 S6 kinase signaling. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-14-04.

Glioblastoma multiforme (GBM) are aggressive and malignant tumors that develop in the brain. These tumors are characterized by increased rates of proliferation and invasive migration as well as angiogenesis. To date few therapeutic options exist for the treatment and management of GBMs, therefore we decided to investigate the anti-oncogenic properties of extracts from the rosehip plant. Rosehip extracts have been used for centuries as alternative therapies. Currently, rosehip extracts are being used as over the counter supplements and recent studies demonstrate that it has an anti-tumor effect. Therefore, we tested the anti-migratory and antiproliferative capacity of extracts from the rosehip (Rosa canina) plant in GBM cell lines. Three human GBM cell lines, U-251 MG, U-1242MG and A-172, were treated with rosehip extracts (1 mg/mL - 25ng/mL) and demonstrated a decrease in cell proliferation. The rosehip extract-mediated decrease in cell proliferation was equal to the decrease of cell proliferation observed when U0126 (10µM), a know inhibitor of GBM cell proliferation was utilized. Utilizing a fluorescent-based labeling strategy (Live-Dead Assay), we examined whether rosehip extracts prevented cell proliferation by initiating apoptosis. Pretreatment of the GBM cells with rosehip extracts (1 mg/mL - 25ng/mL) induced the inhibition of cell proliferation without promoting apoptosis; whereas, cells treated with staurosporine (1 µM), a known inducer of apoptosis, showed an increase in cell apoptosis. Additional studies demonstrated that rosehip extracts prevent GBM cell proliferation by decreasing the active state of MAPK and AKT. Furthermore, rosehip extract-treated GBM cells also prevent cell migration by regulating actin remodeling. Taken together, these data suggest that rosehip extracts inhibit cell proliferation via a cytostatic mechanism that does not by induce apoptosis while also serving as a migration inhibiting agent. These data suggest that, rosehip extracts may serve as an alternative, or supplement, to current therapeutic regimens for GBMs. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1986. doi:1538-7445.AM2012-1986

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