1,721,023 research outputs found
BRM270 suppresses cervical cancer stem cell characteristics and progression by inhibiting SOX2
No full textBackground/Aim: Cervical cancer is one of the leading causes of cancer death in women worldwide. BRM270 (BRMLife) has therapeutic potential for cancer treatment owing to its ability to inhibit cell proliferation, and expression of cluster of differentiation (CD) 133 in CD133+ cancer cells. This study was designed to evaluate the therapeutic effects of plant extract formulation BRM270 against cervical cancer progression. Materials and Methods: The expression of sex-determining region Y-box 2 (SOX2) was tested in four different cervical cancer cell lines, HeLA, SiHa, Caski and C33A. SOX2-expressing SiHa and C33A cell lines were selected for further experiments on the in vitro and in vivo effects of BRM270 on cervical cancer progression using western blotting, flow cytometry, sphere-formation assay, magnetic-activated cell sorting of CD133+ cervical cancer cells, and xenografts in female athymic BALB/c nude mice. Results: In the present study, in cervical cancer stem cells (CSCs), we found that BRM270 inhibited expression of SOX2, which is associated with cervical cancer initiation and metastasis. BRM270 also inhibited CD133 expression and induced apoptosis of CSCs and suppressed CD133+ CSC proliferation and sphere formation in vitro as well as SiHa and C33A cell xenograft tumor growth in vivo. This was accompanied by down-regulation of markers of epithelial-to-mesenchymal transition. Conclusion: BRM270 might be an effective agent for cervical cancer treatment. ⓒ 2020 International Institute of Anticancer Research.
Regulatory function of peroxiredoxin I on 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung cancer development
No full textSmoking is a major cause of lung cancer, and 4？(methylnitrosamino)？1？(3？pyridyl)？1？butanone (NNK) is one of the most important carcinogens in cigarette smoke. NNK modulates the expression of peroxiredoxin (Prdx) I in lung cancer. Prdx1 is upregulated in lung squamous cell carcinoma and lung adenocarcinoma, and considered a potential biomarker for lung cancer. The current article reviewed the role and regulatory mechanisms of Prdx1 in NNK？induced lung cancer cells. Prdx1 protects erythrocytes and DNA from NNK？induced oxidative damage, prevents malignant transformation of cells and promotes cytotoxicity of natural killer cells, hence suppressing tumor formation. In addition, Prdx1 has the ability to prevent NNK？induced lung tumor metabolic activity and generation of large amount of reactive oxygen species (ROS) and ROS？induced apoptosis, thus promoting tumor cell survival. In contrast to this, Prdx1, together with NNK, can promote the epithelial？mesenchymal transition and migration of lung tumor cells. The signaling pathways associated with NNK and Prdx1 in lung cancer cells have been discussed in present review; however, numerous potential pathways are yet to be studied. To develop novel methods for treating NNK？induced lung cancer, and improve the survival rate of patients with lung cancer, further research is needed to understand the complete mechanism associated with NNK.
A1E reduces stemness and self-renewal in HPV 16-positive cervical cancer stem cells
No full textBackground: Cervical cancer is the second most common cancer in females. Recent reports have revealed the critical role of cervical cancer stem cells (CSCs) in tumorigenicity and metastasis. Previously we demonstrated that A1E exerts an anti-proliferative action, which inhibits the growth of cervical cancer cells. Methods: A1E is composed of 11 oriental medicinal herbs. Cervical cancer cell culture, wund healing and invasion assay, flow cytometry, sheroid formation assay, and wstern blot assays were performed in HPV 16-positive SiHa cell and HPV 16-negative C33A cells. Results: A1E targets the E6 and E7 oncogenes; thus, A1E significantly inhibited proliferation of human papilloma virus (HPV) 16-positive SiHa cells, it did not inhibit the proliferation of HPV-negative C33A cells. Accordingly, we investigated whether A1E can regulate epithelial-to-mesenchymal transition (EMT), CSC self-renewal, and stemness-related gene expression in cervical cancer cells. Down rgulation of cell migration, cell invasion, and EMT was observed in A1E-treated SiHa cells. Specifically, A1E-treated SiHa cells showed significant decreases in OCT-3/4 and Sox2 expression levels and in sphere formation. Moreover, CSCs makers ALDH+ and ALDH, CD133 double positive cell were significantly decreased in A1E-treated SiHa cells. However, A1E treatment did not down regulate ALDH+ expression and the number of ALDH/CD133 double positive cells in C33A cells. Conclusions: Taken together, A1E can inhibit CSCs and reduce the expression of stemness markers. Treating CSCs with A1E may be a potential therapy for cervical cancer.open
IL-32θ inhibits stemness and epithelial-mesenchymal transition of cancer stem cells via the STAT3 pathway in colon cancer
No full textInterleukin (IL)-32 is a well-known cytokine associated with inflammation, virus infections and cancer. IL-32θ is a newly identified isoform of IL-32, whose function has yet to be elucidated. In this study, we investigated IL-32θ function in colon cancer stem cells. Using samples from colon cancer patients, we found that the expression of IL-32θ mRNAs was significantly suppressed in tumor regions. We investigated the effects of IL-32θ on colon cancer. Ectopic expression of IL-32θ attenuated invasion, migration in vitro and in vivo tumorigenicity of colon cancer cells. IL-32θ inhibited epithelial-mesenchymal transition (EMT), resulting in the suppression of their migratory and invasive capabilities of HT29 colon cancer cells. In addition, IL-32θ altered various properties of CSCs, including sphere formation and expression of stemness related genes. IL-32θ directly bound to STAT3 and inhibited its nuclear translocation, leading to inhibited transcription of downstream factors, including Bmi1 and ZEB1. We showed that IL-32θ inhibited the STAT3-ZEB1 pathway and consequently inhibited key factors of stemness and EMT. Taken together, our findings reveal that IL-32θ can be a tumor suppressor, indicating that IL-32θ could possibly be used in therapies for colon cancer.open
BRM270 targets cancer stem cells and augments chemo-sensitivity in cancer
No full textOver the past decade, a number of studies have demonstrated the resistance of cancer cells to conventional drugs and have recognized this as a major challenge in cancer therapy. While attempting to understand the underlying mechanisms of chemoresistance, several studies have suggested that the presence of cancer stem cells (CSCs) in tumors is one of the major pathways contributing toward resistance. Chemoresistance leads to cancer treatment failure and worsens the prognosis of patients. Natural herbal compounds are gaining attention as an alternative treatment strategy for cancer. These compounds may be effective against chemoresistant cells either alone or synergistically alongside conventional drugs, sensitizing cancer cells and enhancing the therapeutic efficacy. BRM270 is a natural compound made from seven herbal plant (Saururus chinensis, Citrus unshiu Markovich, Aloe vera, Arnebia euchroma, Portulaca oleracea, Prunella vulgaris var. lilacina and Scutellaria bacicalensis) extracts used in Asian traditional medicine and has the potential to target CSCs. Several studies have demonstrated the positive effects of BRM270 against chemoresistant cancer and its synergy alongside existing cancer drugs, including paclitaxel and gefitinib. These effects have been observed against various cancer types, including resistant non？small cell lung cancer (NSCLC), glioblastoma, multi？drug resistant osteosarcoma, cervical cancer, pancreatic cancer and hepatocarcinoma. The present review discusses the effects of BRM270 treatment against CSC？associated chemoresistance in common types of cance
Wogonin influences osteosarcoma stem cell stemness through ROS-dependent signaling
No full textBackgorund/Aim: Wogonin, a flavonoid-like compound extracted from the root of Scutellaria baicalensis Georgi, has been shown to have anticancer effects against cancer cells. Osteosarcoma is the most malignant type of bone cancer and can appear in any bone, with a high propensity for relapse and metastasis. The present study aimed to assess the anticancer effects of wogonin on osteosarcoma stem cells. Materials and Methods: The cytotoxic effects of wogonin on CD133+ Cal72 osteosarcoma stem cells were assessed through in vitro experiments by MTT assay, transwell assay, sphere-formation assay, flow cytometry, immunocytochemistry and western blotting. Results: Wogonin suppressed stem cell characteristics and the expression of stem cell-related genes by regulating reactive oxygen species (ROS) levels and ROS-related signaling of CD133+ Cal72 cells, effects which were reversed by ROS scavenger N-acetylcysteine. Conclusion: Wogonin may be a promising candidate for successful clinical management of osteosarcoma by regulating ROS-related mechanisms and stem cell-related genes. ⓒ 2020 International Institute of Anticancer Research. All rights reserved.
Mucin 1-mediated chemo-resistance in lung cancer cells
No full textPaclitaxel (PTX) is a commonly used drug to treat diverse cancer types. However, its treatment can generate resistance and the mechanisms of PTX-resistance in lung cancers are still unclear. We demonstrated that non-small cell lung cancers (NSCLCs) survive PTX treatment. Compared with the progenitor NSCLC A549 cells, the PTX-resistant A549 cells (A549/PTX) displayed enhanced sphere-formation ability. The proportion of the cancer stem cell marker, aldehyde dehydrogenase-positive cells, and epithelial-mesenchymal transition signaling protein levels were also elevated in A549/PTX. Importantly, the levels of oncoproteins phosphoinositide-3 kinase/Akt, mucin 1 cytoplasmic domain (MUC1-C) and β-catenin were also significantly elevated in A549/PTX. Furthermore, nuclear translocation of MUC1-C and β-catenin increased in A549/PTX. The c-SRC protein, an activator of MUC1-C, was also overexpressed in A549/PTX. These observations led to the hypothesis that enhanced expression of MUC1-C is associated with stemness and PTX resistance in NSCLCs. To test this, we knocked down or overexpressed MUC1-C in A549/PTX and found that inhibition of MUC1-C expression coupled with PTX treatment was sufficient to reduce the sphere-forming ability and survival of A549/PTX. In summary, our in vitro and in vivo studies have revealed a potential mechanism of MUC1-C-mediated PTX resistance and provided insights into a novel therapeutic measure for lung cancers.open
Luteolin 8-C-β-fucopyranoside downregulates IL-6 expression by inhibiting MAPKs and the NF-κB signaling pathway in human monocytic cells
No full textNumerous studies have been suggested that derivatives can improve the effects of original substances. Therefore, we made luteolin derivative luteolin 8-C-β-fucopyranoside (LU8C-FP) for better anti-inflammatory and anti-cancer effects. In a previous study, we demonstrated that LU8C-FP inhibits invasion of human breast cancer cells via suppression of matrix metalloproteinase 9 and IL-8, which play major roles in tumor progression and cancer cell invasion. Various stimuli trigger inflammatory responses by inducing pro-inflammatory cytokines and chemokines in THP-1 cells. IL-6 induces inflammation via inducing various cytokines and appears to be a potential mediator of inflammatory diseases. Here, we investigated the precise mechanism by which LU8C-FP inhibited phorbol 12-myristate 13-acetate-induced IL-6 mRNA and protein expression. We showed LU8C-FP downregulated IL-6 expression by inhibiting mitogen-activated protein kinases and the nuclear factor-kappaB signaling pathway in human monocytic cells. Furthermore, LU8C-FP exerts less cytotoxicity than luteolin and also it has specific inhibitory effect on IL-6 expression. However, luteolin has a variety of inhibitory effects on pro-inflammatory cytokines and chemokines. Our in vitro studies may provide valuable information leading to the use of LU8C-FP to treat inflammatory diseases caused by IL-6.open
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