Design and Evaluation of Semi-Synthetic Morin Derivatives as Promising Antitumor Agents against Breast and Liver Cancer.

Genes encoding growth-inhibitory proteins are postulated to be candidate tumor suppressors. The identification of such proteins may benefit the early diagnosis and therapy of tumors. Here we report the cloning and functional characterization of a novel human bone marrow stromal cell (BMSC)-derived growth inhibitor (BDGI) by large scale random sequencing of a human BMSC cDNA library. Human BDGI cDNA encodes a 477-amino acid residue protein that shares high homology with rat and mouse pregnancy-induced growth inhibitors. The C-terminal of BDGI is identical to a novel human pregnancy-induced growth inhibitor, OKL38. BDGI is also closely related to many other eukaryotic proteins, which together form a novel and highly conserved family of BDGI-like proteins. BDGI overexpression inhibits the proliferation, decreases anchorage-dependent growth, and reduces migration of MCF-7 human breast cancer cells, whereas down-regulation of BDGI expression promotes the proliferation of MCF-7 and HeLa cervix epitheloid carcinoma cells. Interestingly, the inhibitory effect of BDGI on MCF-7 cells is more potent than that of OKL38. We demonstrate that BDGI induces cell cycle arrest in S phase and subsequent apoptosis of MCF-7 cells, which is likely to account for the antiproliferative effects of BDGI. This process may involve up-regulation of p27Kip1 and down-regulation of cyclin A, Bcl-2, and Bcl-xL. The inhibitory effect of BDGI on cell proliferation and the induction of apoptosis were also observed in A549 lung cancer cells but not HeLa cells. These results indicate that BDGI might be a growth inhibitor for human tumor cells, especially breast cancer cells, possibly contributing to the development of new therapeutic strategies for breast cancer.

Aberrant activity of the phosphatidylinositol 3-kinase (PI3K) pathway supports growth of many tumors including those of breast, lung, and prostate. Resistance of breast cancer cells to targeted chemotherapies including tyrosine kinase inhibitors (TKI) has been linked to persistent PI3K activity, which may in part be due to increased membrane expression of epidermal growth factor (EGF) receptors (HER2 and HER3). Recently we found that proteins of the RGS (regulator of G protein signaling) family suppress PI3K activity downstream of the receptor by sequestering its p85alpha subunit from signaling complexes. Because a substantial percentage of breast tumors have RGS16 mutations and reduced RGS16 protein expression, we investigated the link between regulation of PI3K activity by RGS16 and breast cancer cell growth. RGS16 overexpression in MCF7 breast cancer cells inhibited EGF-induced proliferation and Akt phosphorylation, whereas shRNA-mediated extinction of RGS16 augmented cell growth and resistance to TKI treatment. Exposure to TKI also reduced RGS16 expression in MCF7 and BT474 cell lines. RGS16 bound the amino-terminal SH2 and inter-SH2 domains of p85alpha and inhibited its interaction with the EGF receptor-associated adapter protein Gab1. These results suggest that the loss of RGS16 in some breast tumors enhances PI3K signaling elicited by growth factors and thereby promotes proliferation and TKI evasion downstream of HER activation.

Vitamin D(3) compounds are currently in clinical trials for human breast cancer and offer an alternative approach to anti-hormonal therapies for this disease. 1alpha,25-Dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), the active form of vitamin D(3), induces apoptosis in breast cancer cells and tumors, but the underlying mechanisms are poorly characterized. In these studies, we focused on the role of caspase activation and mitochondrial disruption in 1alpha,25(OH)(2)D(3)-mediated apoptosis in breast cancer cells (MCF-7) in vitro. The effect of 1alpha,25(OH)(2)D(3) on MCF-7 cells was compared with that of tumor necrosis factor alpha, which induces apoptosis via a caspase-dependent pathway. Our major findings are that 1alpha,25(OH)(2)D(3) induces apoptosis in MCF-7 cells by disruption of mitochondrial function, which is associated with Bax translocation to mitochondria, cytochrome c release, and production of reactive oxygen species. Moreover, we show that Bax translocation and mitochondrial disruption do not occur after 1alpha,25(OH)(2)D(3) treatment of a MCF-7 cell clone selected for resistance to 1alpha,25(OH)(2)D(3)-mediated apoptosis. These mitochondrial effects of 1alpha,25(OH)(2)D(3) do not require caspase activation, since they are not blocked by the cell-permeable caspase inhibitor z-Val-Ala-Asp-fluoromethylketone. Although caspase inhibition blocks 1alpha,25(OH)(2)D(3)-mediated events downstream of mitochondria such as poly(ADP-ribose) polymerase cleavage, external display of phosphatidylserine, and DNA fragmentation, MCF-7 cells still execute apoptosis in the presence of z-Val-Ala-Asp-fluoromethylketone, indicating that the commitment to 1alpha,25(OH)(2)D(3)-mediated cell death is caspase-independent.

Estrogen antagonists are universally employed in the breast cancer therapy, although antagonist therapy is limited by the inevitable development of cellular resistance. The molecular mechanisms by which these agents inhibit cellular proliferation in breast cancer cells are not fully defined. Recent studies have shown the involvement of the E2F pathway in tamoxifen-induced growth arrest. We show that an E2F repressor, prohibitin, and the chromatin modifiers Brg1/Brm are required for estrogen antagonist-mediated growth suppression through the estrogen receptor, and that their recruitment to native promoter-bound E2F is induced via a JNK1 pathway. In addition, we demonstrate major mechanistic differences among the signaling pathways initiated by estrogen, estrogen deprivation, and estrogen antagonists. Collectively, these findings suggest that the prohibitin/Brg1/Brm node is a major cellular target for estrogen antagonists, and thereby also implicate prohibitin/Brg1/Brm as potentially important targets for breast cancer therapy.

We explored the role of microRNAs (miRNAs) in acquiring resistance to tamoxifen, a drug successfully used to treat women with estrogen receptor-positive breast cancer. miRNA microarray analysis of MCF-7 cell lines that are either sensitive (parental) or resistant (4-hydroxytamoxifen-resistant (OHT(R))) to tamoxifen showed significant (>1.8-fold) up-regulation of eight miRNAs and marked down-regulation (>50%) of seven miRNAs in OHT(R) cells compared with parental MCF-7 cells. Increased expression of three of the most promising up-regulated (miR-221, miR-222, and miR-181) and down-regulated (miR-21, miR-342, and miR-489) miRNAs was validated by real-time reverse transcription-PCR. The expression of miR-221 and miR-222 was also significantly (2-fold) elevated in HER2/neu-positive primary human breast cancer tissues that are known to be resistant to endocrine therapy compared with HER2/neu-negative tissue samples. Ectopic expression of miR-221/222 rendered the parental MCF-7 cells resistant to tamoxifen. The protein level of the cell cycle inhibitor p27(Kip1), a known target of miR-221/222, was reduced by 50% in OHT(R) cells and by 28-50% in miR-221/222-overexpressing MCF-7 cells. Furthermore, overexpression of p27(Kip1) in the resistant OHT(R) cells caused enhanced cell death when exposed to tamoxifen. This is the first study demonstrating a relationship between miR-221/222 expression and HER2/neu overexpression in primary breast tumors that are generally resistant to tamoxifen therapy. This finding also provides the rationale for the application of altered expression of specific miRNAs as a predictive tamoxifen-resistant breast cancer marker.

Progression of breast cancer implicates the degradation of extracellular matrix (ECM) by metallo-proteinases (MMPs), a process with important consequences on the growth and invasiveness of cancer cells in adjacent and distant sites. The isoflavone, genistein--a natural inhibitor of protein tyrosine kinase pathway--inhibits the growth of a wide range of cancer cells in vitro. The aim of this study was to investigate: i) the expression of mRNAs encoded for MMPs and their endogenous inhibitors (TIMPs) associated with pathogenesis and metastatic potential of breast cancer cells; and ii) the effect of genistein on the transcription of MMPs and TIMPs and the invasive potential of breast cancer cells. Gene expression at transcriptional level was examined in cell cultures of two epithelial breast cancer cell lines, the high invasive (ER-negative) MDA-MB-231 and the low invasive (ER-positive) MCF-7, as well as the normal mammary cells (MCF-12A) following RNA isolation and reversed transcriptase polymerase chain reaction (RT-PCR). The inhibitory effect of genistein on functional invasiveness was examined by a cell invasion assay. Cell cycle distribution showed that genistein arrested breast cancer MDA-MB-231, MCF-7 and BT-20 cells in the G2/M phase. Both normal and breast cancer cell lines express the genes of MMP-2, -9, MT1-, MT2-, MT3-MMP and TIMP-1, -2 and -3. MCF-7 express notably less MMPs than MDA-MB-231 cell line. The addition of genistein resulted in down-regulation of the transcription of all MMP genes in MDA-MB-231 and most of MMPs in MCF-7 cells. The inhibitory effect of genistein on MMPs was functionally confirmed, since it significantly reduced the invasion properties of cancer cells in vitro. The obtained results indicate that genistein may be of great value in prevention of breast cancer cell metastasis, since it represents both a transcriptional modulator of genes involved in this pathogenetic process and a suppressor of breast cancer cell invasiveness.

Hepatocellular carcinoma and breast cancer are the most prevalent cancers in the world with high morbidity and mortality. Although there are effective drugs for treating advanced stages of liver and breast cancers, the prognosis for patients with liver cancer remains poor, and patients with breast cancer show considerable mortality. Therefore, it is crucial to explore new therapeutic agents for the inhibition of carcinogenesis. This study examined the anti-carcinogenic effect of Vitis labrusca seed extract (VLE), which is a component of winery waste, on liver (HepG2) and breast cancers (MCF-7) cells. The results found in this study demonstrated VLEinduced DNA damage in liver and breast cancer cells. VLE treatment in both cell lines was accompanied by high NO production and upregulation of p53. A significant decrease in total PARP expression was also found in HepG2 cells. In the MCF-7 cell line, VLE treatment increased the expression of Bax and AIF, and decreased total PARP expression. Surprisingly, VLE suppressed Her-2 expression in HepG2 cells and caused a subtle, but significant downregulation of Her-2 in MCF-7 cells. The possible anti-carcinogenic effect of VLE reported in this study suggests the potential of this extract to be used for the development of novel therapeutic agents for the treatment of different kinds of cancers.

Accumulating evidence suggest that the pyridine nucleotide NAD has far wider biological functions than its classical role in energy metabolism. NAD is used by hundreds of enzymes that catalyze substrate oxidation and, as such, it plays a key role in various biological processes such as aging, cell death, and oxidative stress. It has been suggested that changes in the ratio of free cytosolic [NAD(+)]/[NADH] reflects metabolic alterations leading to, or correlating with, pathological states. We have designed an isotopically labeled metabolic bioprobe of free cytosolic [NAD(+)]/[NADH] by combining a magnetic enhancement technique (hyperpolarization) with cellular glycolytic activity. The bioprobe reports free cytosolic [NAD(+)]/[NADH] ratios based on dynamically measured in-cell [pyruvate]/[lactate] ratios. We demonstrate its utility in breast and prostate cancer cells. The free cytosolic [NAD(+)]/[NADH] ratio determined in prostate cancer cells was 4 times higher than in breast cancer cells. This higher ratio reflects a distinct metabolic phenotype of prostate cancer cells consistent with previously reported alterations in the energy metabolism of these cells. As a reporter on free cytosolic [NAD(+)]/[NADH] ratio, the bioprobe will enable better understanding of the origin of diverse pathological states of the cell as well as monitor cellular consequences of diseases and/or treatments.

The liver is a common site of metastasis in metastatic breast cancer and is associated with significant mortality. Histopathological examination of human breast cancer liver metastases (BCLMs) reveals that the majority of these tumours present with a ‘replacement growth pattern.’ In this growth pattern, the breast cancer cells freely invade the liver parenchyma and replace the resident hepatocytes. In advanced BCLMs, breast cancer cells can eventually replace a significant volume of the liver parenchyma which, ultimately, leads to organ failure and death. However, the mechanism through which breast cancer cells replace the resident hepatocytes is unknown. Here we set out to establish how this replacement of hepatocytes by breast cancer cells occurs in BCLMs. To do so, we established two in vivo models of advanced BCLM: (a) an ER+PR+HER2- model using the MCF7 cell line, and (b) a triple negative patient-derived xenograft model using breast cancer cells isolated from a pleural effusion. We have also established an in vitro co-culture system, where MCF7 cells are co-cultured with HepG2 cells, which is designed to mimic the breast cancer cell-hepatocyte interaction observed in vivo. Both in vivo models exhibit a histology that closely mimics the replacement growth pattern of human BCLMs, where breast cancer cells replace hepatocytes at the tumour-liver interface. To address whether hepatocytes are killed by adjacent breast cancer cells in vivo, we evaluated hepatocyte death by apoptosis using appropriate markers (cleaved-PARP and cleaved-caspase-3). Surprisingly, although extensive apoptotic death of breast cancer cells in the tumour mass could be observed, no evidence for apoptotic death of hepatocytes could be found. However, we observed extensive cell-in-cell invasion at the tumour-liver interface, where live breast cancer cells enter the cytoplasm of adjacent hepatocytes. We also observe a similar process of cell-in-cell invasion within in vitro cultures of MCF-7 cells with HepG2 cells. Although cell-in-cell invasion has been described as a mechanism of non-apoptotic cell death in breast cancer cells, the role of cell-in-cell invasion between breast cancer cells and hepatocytes in BCLMs has not been investigated. Our current studies are focused in two areas: (a) we are using intra-vital microscopy and time-lapse microscopy to investigate whether cell-in-cell invasion between breast cancer cells and hepatocytes mediates non-apoptotic death of hepatocytes both in vivo and in vitro, and (b) we are investigating the molecular mechanisms that mediate cell-in-cell invasion between breast cancer cells and hepatocytes. In conclusion, we present preliminary evidence for a novel mechanism via which breast cancer cells could replace hepatocytes in BCLMs. Further studies aimed at elucidating the molecular basis of this mechanism may reveal novel targets for preventing the replacement of the liver parenchyma by metastatic breast cancer cells. Citation Format: Mark R. Nathan, Lefteris Kostaras, Victoria Bridgeman, Shane Foo, Peter Vermeulen, Andrew Reynolds. Dissecting the mechanisms of hepatocyte replacement in breast cancer liver metastases. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4105.

Dual-miRNA-Propelled Three-Dimensional DNA Walker for Highly Specific and Rapid Discrimination of Breast Cancer Cell Subtypes in Clinical Tissue Samples

A chylomicron-mimicking lipid emulsion was prepared and loaded with paclitaxel (paclitaxel-CM) and was further grafted with galactose (paclitaxel-GCM) using palmitoyl-galactosamine, which was synthesized by reacting galactosamine hydrochloride with N-hydroxy succinimide ester of palmitic acid. Palmitoyl-galactosamine was used as a ligand for asialoglycoprotein receptors. The uptake characteristics of the emulsions were evaluated in HepG-2 cells (human hepatocarcinaoma), which express asialoglycoprotein receptors, and MCF-7 (breast cancer) cells, which are devoid of these receptors. The incorporation efficiency of paclitaxel-CM was 68.05 +/- 4.80% and that of paclitaxel-GCM was 72.10 +/- 3.93% when the emulsion was prepared with 7.5% (w/w) paclitaxel/lipid phase. The globule size of paclitaxel-GCM and paclitaxel-CM was 124 +/- 8.67 and 96.45 +/- 5.78 nm, respectively. The release of paclitaxel from both of the formulations was fairly sustained: 50 +/- 3.2% of paclitaxel in 24 h. The cytotoxicity and uptake of paclitaxel-GCM were significantly higher (P < 0.05) in HepG-2 cells than MCF-7 cells, while for paclitaxel-CM cytotoxicity and uptake were similar in the two cell lines. This study clearly demonstrates that upon surface modification palmitoyl-galactosamine remains an integral part of the formulation. Paclitaxel solubility can be improved using optimum paclitaxel/lipid phase ratios. The paclitaxel-GCM formulation recognizes asialoglycoprotein receptors overexpressed on HepG-2 cells. Under our experimental conditions, the proposed paclitaxel-GCM formulation is an ideal delivery vehicle for specific targeting to liver cancer cells, which is anticipated to result in improved efficacy and reduced toxicity to normal cells.

Objectives A chylomicron-mimicking lipid emulsion was prepared and loaded with paclitaxel (paclitaxel-CM) and was further grafted with galactose (paclitaxel-GCM) using palmitoyl-galactosamine, which was synthesized by reacting galactosamine hydrochloride with N-hydroxy succinimide ester of palmitic acid. Palmitoyl-galactosamine was used as a ligand for asialoglycoprotein receptors. Methods The uptake characteristics of the emulsions were evaluated in HepG-2 cells (human hepatocarcinaoma), which express asialoglycoprotein receptors, and MCF-7 (breast cancer) cells, which are devoid of these receptors. Key findings The incorporation efficiency of paclitaxel-CM was 68.05 ± 4.80% and that of paclitaxel-GCM was 72.10 ± 3.93% when the emulsion was prepared with 7.5% (w/w) paclitaxel/lipid phase. The globule size of paclitaxel-GCM and paclitaxel-CM was 124 ± 8.67 and 96.45 ± 5.78 nm, respectively. The release of paclitaxel from both of the formulations was fairly sustained: 50 ± 3.2% of paclitaxel in 24 h. The cytotoxicity and uptake of paclitaxel-GCM were significantly higher (P &amp;lt; 0.05) in HepG-2 cells than MCF-7 cells, while for paclitaxel-CM cytotoxicity and uptake were similar in the two cell lines. This study clearly demonstrates that upon surface modification palmitoyl-galactosamine remains an integral part of the formulation. Paclitaxel solubility can be improved using optimum paclitaxel/lipid phase ratios. The paclitaxel-GCM formulation recognizes asialoglycoprotein receptors over-expressed on HepG-2 cells. Conclusions Under our experimental conditions, the proposed paclitaxel-GCM formulation is an ideal delivery vehicle for specific targeting to liver cancer cells, which is anticipated to result in improved efficacy and reduced toxicity to normal cells.

Breast and colorectal cancers are among the most common tumor types worldwide and the occurrence of metastases is often associated with a shortened lifespan. One of the signaling pathways that has been frequently associated with metastasis in these tumor entities is the Wnt signaling pathway. Wnt signaling can be either β-catenin dependent (canonical) or βcatenin independent (non-canonical). In breast and colorectal cancer, tumor-promoting properties could be attributed to members of the non-canonical Wnt signaling pathway. Preliminary results showed that overexpression of ROR2 as a non-canonical Wnt receptor, mediated an aggressive phenotype in breast cancer cells and could significantly increase invasion. Accordingly, the first aim of this work was to investigate which ligand binds ROR2 and thus triggers the invasive behavior of MCF-7 cells. RNA-seq analysis revealed increased expression levels of the non-canonical ligand Wnt11 in ROR2 overexpressing cells. Hence, Wnt11 was further investigated as a potential ROR2-ligand. Using co-immunoprecipitation experiments, this work demonstrated the interaction of ROR2 with Wnt11 in human breast cancer cells. To determine which domain facilitates the ROR2-mediated invasion, sequential deletions of the different ROR2 domains were induced. This demonstrated that the cysteine-rich and the tyrosine kinase domain mediate this effect. The next step was to determine whether Wnt11 binds other receptors that trigger the invasive behavior of MCF-7 cells since ROR2 is not expressed in these cells. Furthermore, a cell line screening of different breast and colorectal cancer cell lines identified FZD4 and FZD6 as highly expressed non-canonical Wnt receptors. An interaction between Wnt11 and FZD6 was validated by using Co-IP, in which PTK7 appears to act as a co-receptor. To investigate functional implications of Wnt11-mediated signaling in breast cancer, MCF-7 cells were stimulated with recombinant Wnt11, which caused increased invasion and migration rates, whereas loss of FZD6 resulted in a significant decrease of the elevated invasion rates. In line with the collected data, a signature with non-canonical Wnt pathway members including FZD receptors, ROR receptors, Wnt ligands and PI3K signaling members was defined and was analyzed for its DMFS prognostic values in breast and colorectal cancer patients. Therefore, the signature was applied to gene expression data of primary breast and colorectal cancer patients. For the primary breast cancer patients, the signature clustered the data set into two patient groups, among which the group with high Wnt11 expression was associated with poor DMFS. Considering FZD4 and FZD6 individually, breast cancer patients with high FZD6 gene expression showed worse DMFS, while high FZD4 levels were associated with favorable DMFS. Interestingly, the defined signature clustered the data set of the colorectal cancer patients into four groups and the cohort with a high FZD6 expression exhibited a poor DMFS compared to the other groups. Another important aspect of tumor progression is the reprogramming of the tumor microenvironment. It has been shown that tumor-derived extracellular vesicles can influence the tumor microenvironment in different ways. Preliminary data demonstrated that Wnt proteins can be transported via extracellular vesicles to target cells and induce Wnt signaling responses there. It was shown that RORs are transported on microvesicles and exosomes. Modulation of ROR1 and ROR2 expression resulted in altered protein compositions for both vesicle populations. However, no major impact on vesicle size or concentration was evident. Further analysis addressed functional consequences of ROR1 and ROR2 expression on extracellular vesicles. Tumor-derived EVs isolated from the aggressive breast cancer cell line MDA-MB231 induced invasiveness in MCF-7 cells, which was shown to be dependent on vesicular ROR1 expression. To determine whether ROR1/2 can function as a biomarker in breast cancer patients, plasma-derived microvesicles were analyzed for their ROR1 and ROR2 expression by flow cytometry, which is currently ongoing. In conclusion, this work demonstrated the importance of non-canonical Wnt signaling in breast cancer progression. Wnt11 has been identified as a novel ligand for ROR2 and FZD6 by co-immunoprecipitation experiments, thereby mediating tumor-promoting properties in breast cancer. In particular, it has been shown that ROR proteins not only play an important role in breast cancer cells themselves, but also appear to be additionally involved in vesicle biogenesis and can furthermore be transferred to target cells. A clinical applicability of both ROR proteins regarding their usage as tumor biomarkers for breast cancer is still under investigation.

Introduction: We have previously demonstrated that chondroitin sulfates (CS) play a crucial role in metastatic potential of breast cancer cells. We have shown that the expression level of carbohydrate (chondroitin 4) sulfotransferase-11 (CHST11) correlates with CS-A expression and aggressiveness of human breast cancer cells. The current study was mainly performed to determine whether the expression of CHST11 gene in breast cancer cells is controlled by DNA methylation. Methods: Quantitative real-time PCR was used to detect the expression of CHST11 in human breast cancer cell lines. MCF7 cells were treated with 5-aza-2′-deoxycytidine (5AzadC) for DNA demethylation and expression analysis. Methylation in MCF7, MDA-MB-231 cells and patient breast cancer specimens was analyzed using bisulfite genomic sequencing (BGS). Reduced representation bisulfite sequencing (RRBS) was performed in the CpG island of CHST11 with a minimum coverage of 10. Digital gene expression was used to estimate the number of transcribed copies of the CHST11 gene from the second-generation mRNA-sequencing data. Results: Treatment of MCF7 cells with 5-AzadC increased the expression of CHST11 and its product CS-A in a dose-dependent manner. We observed very low levels of DNA methylation in a CpG island of CHST11 in estrogen receptor-negative basal-like cell lines MDA-MB-231, MDA-MB-468, and BT-20, but very high levels in the same region in estrogen receptor-positive luminal MCF7, ZR-75-1, and T47-D cells. We found that the CpG island can also be hypomethylated in triple negative (negative for estrogen and progesterone receptors and Her2/neu) patient breast cancer tissues. Conclusions: The data suggest that DNA hypomethylation significantly contributes to CHST11 and surface CS-A expression in aggressive breast cancer cells. The data suggest that therapeutic use of DNA demethylating agents may promote more aggressive forms of breast cancer. 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 4018. doi:1538-7445.AM2012-4018

Background: Pak-Sian Dong is a fermented vegetable product of Thailand prepared from aerial parts of Pak-Sian (Gynandropsis pentaphylla DC.). Lactobacillus plantarum KK518 was isolated from Pak-Sian Dong and already assessed for its probiotic attributes. Objective: The aim of this work was to determine the untapped cytotoxic effects of L. plantarum KK518 extract against HepG2 (liver cancer), MCF-7 (breast cancer) and HeLa (cervical cancer) cells. Materials and Methods: The bacterial extracts were prepared from whole cultures; containing cells and broths using ethyl acetate as extracting solvent and the dried extracts were redissolved in ethanol before use. Cytotoxic, antiproliferative and antimigratory effects of the bacterial extracts on three types of cancer cells were determined using 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetra zolium bromide (MTT) assay, clonogenic formation and wound healing assays, respectively. Results: L. plantarum KK518 extract showed the highest cytotoxicity at 90.88% at 1,000 g/mL against HeLa cells (IC 50 of 371.97 g/mL) over 48 h of exposure. Anti-colony formation test showed that the bacterial extracts at 600, 800 and 1,000 g/mL over 48 h led to a complete inhibition of colony formation of HeLa cells; however the highest IC 50 of 418.52 g/mL was found in HepG2 cells suggesting that HepG2 was least affected by bacterial extract. Likewise, HepG2 cells seemed to be most resistant to antimigratory effects as observed by highest relative area of the wound at most time intervals and most extract concentrations. Conclusion: L. plantarum KK518 offers a potential use as a bio-therapeutic with chemopreventive effects against cervical, breast and liver cancers.