• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5697-5701
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• 2015

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of antioxidative properties. Punica granatum (PG) (pomegranate) is a well known fruit in this context, but its cytotoxicity in cancer cells has not been extensively studied. Here, we investigated the antiproliferative properties of a peel extract of PG from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate peel (PPE) was prepared. Total phenolic content(TPC) and total flavonoid conetnt (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. The cytotoxicity of different doses of PPE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison with negative controls at all tested doses (5-$1000{\mu}g/ml$). In all studied cancer cells, PPE reduced the cell viability to values below 40%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, MCF-7 breast adenocarcinoma cells were the most responsive cells to antiprolifreative effects of PPE with a maximum mean growth inhibition of 81.0% vs. 69.4%, 79.3% and 77.5% in SKOV3, PC-3 and A549 cells, respectively. Conclusions: Low doses of PPE exert potent anti-proliferative effects in different human cancer cells and it seems that MCF-7 breast adenocarcinoma cells are the most cells and SKOV3 ovarian cancer cells the least responsive in this regard. However, the mechanisms of action need to be addressed.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5855-5860
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• 2013

Phytochemicals are among the natural chemopreventive agents with most potential for delaying, blocking or reversing the initiation and promotional events of carcinogenesis. They therefore offer cancer treatment strategies to reduce cancer related death. One such promising chemopreventive agent which has attracted considerable attention is sulforaphane (SFN), which exhibits anti-cancer, anti-diabetic, and anti-microbial properties. The present study was undertaken to assess effect of SFN alone and in combination with a chemotherapeutic agent, gemcitabine, on the proliferative potential of MCF-7 cells by cell viability assay and authenticated the results by nuclear morphological examination. Further we analyzed the modulation of expression of Bcl-2 and COX-2 on treatment of these cells with SFN by RT-PCR. SFN showed cytotoxic effects on MCF-7 cells in a dose- and time-dependent manner via an apoptotic mode of cell death. In addition, a combinational treatment of SFN and gemcitabine on MCF-7 cells resulted in growth inhibition in a synergistic manner with a combination index (CI)<1. Notably, SFN was found to significantly downregulate the expression of Bcl-2, an anti-apoptotic gene, and COX-2, a gene involved in inflammation, in a time-dependent manner. These results indicate that SFN induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 and COX-2 respectively. The combination of SFN and gemcitabine may potentiate the efficacy of gemcitabine and minimize the toxicity to normal cells. Taken together, SFN may be a potent anti-cancer agent for breast cancer treatment.

• Journal of Nutrition and Health
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• v.40 no.2
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• pp.147-153
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• 2007

In this study, we investigated the anticancer activity of the fin of Thunnus Thynnus (TT). TT was extracted with methanol (TTM), and then further fractionated into four subfractions by using solvent partition method, affording hexane (TTMH), methanol (TTMM), butanol (TTMB) and aquous (TTMA) soluble fractions. We determined the cytotoxicity of these four fractions in four kind of cancer cell lines, such as HepG2, MCF-7, B16-F10 and HT29 by MTT assay. The TTMM showed the strongest cytotoxic effect at the concentration of 150 ${\mu}g/mL$, displaying 95% on the HepG2 cell lines and 82% on MCF-7 cell line. The morphological changes such as membrane shirinking and blebbing of cells were also observed by TTMM treatment in HT29 cell. In addition, we observed that quinone reductase (QR) activity was elevated by only TTMM and TTMH treatments in HepG2 cell. QR activity was increased to around 2.0 and 1.8 times in TTMM and TTMH treated HepG2 cell at 100 ${\mu}g/mL$, respectively, compared to that in control. Although further studies are needed, the present work could suggest that the fin of TT has a potential to be usable as a chemopreventive agent against cancer.

• Journal of the Korean Society of Food Science and Nutrition
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• v.31 no.1
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• pp.136-142
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• 2002

Anticarcinogen is one of the major strategies for cancer control. It is well established that dietary factors play an important role in modulating the development of certain types of human cancer. We investiagted the anticarcinogenic effects of Sedum sarmentosum Bunge (SS) with Platycodon grandiflorum A. extracts on HepG2, HeLa and MCF-7 cell lines. By the MTT assay, among the five partition layers of methanol extract of SS (SSM), the ethylether partition layer of SS (SSMEE) showed the strongest cytotoxic effects on all cell lines. We also investigated the synergistic effect of the combination of SS and PG extracts on growth inhibition of the HepG2, HeLa and MCF-7 cell lines compared to the effects of five partition layers of SSM. Combination of SS and PG extracts significantly increased cytotoxic effects on all cell lines. Therefore, we were able to conclude that ethylether partition layer, SSMEE might have potentially useful cytotoxic materials on all the human cancer cells which we used. And we could suggest that the combination of SS with PG enhanced the anticarcinogenic effect on HepG2, HeLa and MCF-7 cell lines. We also determined QR activity of partition layers of SSM, among them, SSMEE on HepG2 cells showed the highest QR activity, 3.21 as control value of 1.0.

• Journal of Life Science
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• v.8 no.6
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• pp.638-647
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• 1998

Protein Kinase C (PKC) activators, phorbol 12-myristate 13-acetate (PMA), bryostatin, and dioctanoyl glycerol (DiC8), induce translocation of PKC isozymes from cytoplasm to plasma membrane or into nucleus. The activated PKC negatively modulates growth of human breast cancer cells. Antiproliferative effect and translocation of PKC were investigated in MCF-7 cells. The translocation of activated PKC isozymes by PMA, bryostatin and DiC8 was occurred at the various different regions in MCF-7 cell. PKC $\alpha$ and $\beta$ could be translocated to the nucleus or the nuclear mem-brane, and PKC $\delta$and $\varepsilon$ to cell membrane by PMA while DiC8 and bryostatin induced the translocation of PKC $\alpha$ and $\beta$ to the nucleus or plasma membrane, respectively. In the antiproliferative effect of PKC activators, PMA ($IC_{50}$/ values of 1.2$\pm$0.3nM) and DiC8 ($IC_{50}$/ values of 5.0$\pm$1.1$\mu$M) inhibited the cell growth. Bryostatin also inhibited the cell growth but to a much less degree than one obser-ved with PMA : 16% growth reduction by 100nM bryostatin. However, PMA treated with bryostatin induced gro-wth inhibition, but PMA with DiC8 at 10$\mu$M was not effective. These results suggest that each PKC isozyme is tran-slocated to various specific sites, and that especially, PKC $\alpha$ isozyme plays an important role in control of antiprolife-raive function of cell growth.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5687-5692
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• 2013

Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta ($PKC{\delta}$)-phosphorylation. Administration of the specific $PKC{\delta}$ inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, $PKC{\delta}$ inhibition by both rottlerin and $PKC{\delta}$ shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that $PKC{\delta}$-dependent ubiquitin proteasome system activation plays an important role in high glucose-induced breast cancer cell growth and metastasis.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3191-3196
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• 2013

Leaf extracts of Cassia alata L (akapulko), traditionally used for treatment of a variety of diseases, were evaluated for their potential antitumor properties in vitro. MTT assays were used to examine the cytotoxic effects of crude extracts on five human cancer cell lines, namely MCF-7, derived from a breast carcinoma, SK-BR-3, another breast carcinoma, T24 a bladder carcinoma, Col 2, a colorectal carcinoma, and A549, a nonsmall cell lung adenocarcinoma. Hexane extracts showed remarkable cytotoxicity against MCF-7, T24, and Col 2 in a dose-dependent manner. This observation was confirmed by morphological investigation using light microscopy. Further bioassay-directed fractionation of the cytotoxic extract led to the isolation of a TLC-pure isolate labeled as f6l. Isolate f6l was further evaluated using MTT assay and morphological and biochemical investigations, which likewise showed selectivity to MCF-7, T24, and Col 2 cells with $IC_{50}$ values of 16, 17, and 17 ${\mu}g/ml$, respectively. Isolate f6l, however, showed no cytotoxicity towards the non-cancer Chinese hamster ovarian cell line (CHO-AA8). Cytochemical investigation using DAPI staining and biochemical investigation using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-a method used to detect DNA fragmentation-together with caspase assay, demonstrated apoptotic cell death. Spectral characterization of isolate f6l revealed that it contained polyunsaturated fatty acid esters. Considering the cytotoxicity profile and its mode of action, f6l might represent a new promising compound with potential for development as an anticancer drug with low or no toxicity to non-cancer cells used in this study.

• Preventive Nutrition and Food Science
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• v.12 no.4
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• pp.197-201
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• 2007

Genistein is an active component of legumes and other related food shown to be associated with prevention of degenerative diseases such as cancer through inducing signaling pathways. Treatment of genistein resulted in the induction of apoptosis in the cultured cancer cells. This induction of apoptosis was demonstrated by the Tunel assay in these cells. Unveiling the potential of genistein in cytotoxicity via apoptosis when it is treated with estrogen can predict the therapeutic capability of genistein in breast cancers in the presence of endogenous estrogen. We have found that apoptosis induced by genistein treatment in the presence of estrogen is agonistic or antagonistic depending on the concentrations and treatment periods applied in MCF-7 breast cancer cells. For the suppression of cell survival, 24 hr of treatment was required to induce a synergistic agonistic response between estrogen and genistein at low concentrations of genistein. After this period, the agonistic pattern of genistein to estrogen disappeared. The decrement of COX-2 expression in MCF-7 cells treated with genistein was accompanied with the activation of AMPK only at a high concentration of genistein. This association between AMPK activation and down-regulation of COX-2 by genistein was dampened in the presence of estrogen. It was also demonstrated that genistein and estrogen regulate cell survival and apoptosis by modulating p53 and caspase-3 in the opposite direction. These results suggest that genistein has the potential to control breast cancer development, and co-treatment with estrogen can cause agonistic or antagonistic action on breast cancer cell control.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.1
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• pp.179-184
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• 2014

Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of $80{\mu}M$, $21{\mu}M$, and $82{\mu}M$ respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF-kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.

• Journal of Life Science
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• v.19 no.9
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• pp.1251-1257
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• 2009

We investigated the growth inhibitory effect of internal organs of Todarodes pacificus (TP) on proliferation in human cancer cell lines in vitro. The internal organs of TP were extracted with methanol (TPM), which was then further fractionated into four subfractions by using a solvent partition method, resulting in hexane (TPMH), methanol (TPMM), butanol (TPMB), and aqueous (TPMA) soluble fractions. We determined the cytotoxic effect of these four fractions in three kinds of cancer cell lines - HepG2, MCF-7 and HT-29 - by MTT assay. Among the four subfractions of TPM, TPMH showed the strongest cytotoxic effects at a concentration of $300{\mu}g$/ml, displaying 91.56% on the HepG2 cell line and 85.93% on the MCF-7 cell line. Morphological changes such as membrane shirinking and blebbing of cells were also observed during TPMH treatment of HepG2 cells. In addition, we also observed quinone reductase (QR) induced effect in the methanol (TPMM) layer of HepG2 cells. TPMM showed the highest induction activity of quinone reductase on HepG2 cells among the other partition layers. The QR induced effect of TPMM was determined to be 2.7 at a level of $360{\mu}g$/ml with a control value of 1.0. Although further studies are needed, the present work suggests that internal organs of Todarodes pacificus (TP) may be a chemopreventive agent for the treatment of human cells.