2014/11/17

Berberine induces apoptosis

berberine kills cancer cells

Berberine affects human cancer cells

1. Mol Med Rep. 2014 Dec;10(6):3132-8. doi: 10.3892/mmr.2014.2608. Epub 2014 Oct 8.

Berberine sensitizes rapamycin‑mediated human hepatoma cell death in vitro.

Guo N(1), Yan A(1), Gao X(1), Chen Y(2), He X(1), Hu Z(1), Mi M(1), Tang X(3), Gou X(1). Author information:  (1)Laboratory of Cell Biology and Translational Medicine, Institute of Basic Medical Science, X'ian Medical University, Xi'an, Shaanxi 710021, P.R. China. (2)Department of Cell Biology and Genetics, College of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710032, P.R. China. (3)Department of Pathology, Sichuan College of Traditional Chinese Medicine, Mianyang, Sichuan 721000, P.R. China. Rapamycin is clinically used as an immunosuppressant. Increasing evidence suggests that rapamycin has an important inhibitory role in the development and progression of different types of cancer and that it is a promising candidate for cancer chemotherapy. Berberine is an isoquinoline alkaloid isolated from medicinal plant species, which has been used in traditional Chinese medicine with no significant side effects. Recent research has demonstrated that berberine has anticancer activity against various types of cancer, mediated through the suppression of mammalian target of rapamycin (mTOR). The present study aimed to investigate the in vitro synergistic anticancer effect of combined treatment of rapamycin at various concentrations (0, 10, 50, 100 and 200 nM) and berberine (62.5 µM) in SMMC7721 and HepG2 hepatocellular carcinoma (HCC) cell lines, and the potential underlying molecular mechanism. The combined use of rapamycin and berberine was found to have a synergistic cytotoxic effect, with berberine observed to maintain the cyotoxic effect of rapamycin on HCC cells at a lower rapamycin concentration. Moreover, the cells treated with the combination of the two agents exhibited significantly decreased protein levels of phosphorylated (p)‑p70S6 kinase 1 (Thr389), the downstream effector of mTOR, compared with the cells treated with rapamycin or berberine alone. Furthermore, overexpression of cluster of differentiation (CD) 147, a transmembrance glycoprotein associated with the anticancer effects of berberine, was found to upregulate p‑mTOR expression and inhibit cell death in SMMC7721 cells co‑treated with rapamycin and berberine. In conclusion, the findings of the present study suggest that the combined use of rapamycin and berberine may improve HCC therapy through synergistically inhibiting the mTOR signaling pathway, which is at least in part, mediated through CD147.




2. Mol Med Rep. 2014 Nov 12. doi: 10.3892/mmr.2014.2929. [Epub ahead of print]

Berberine targets epidermal growth factor receptor signaling to suppress prostate cancer proliferation in vitro.

Huang ZH, Zheng HF, Wang WL, Wang Y, Zhong LF, Wu JL, Li QX. Author information: Department of Urological Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, Jiangsu 215300, P.R. China. Berberine is a well‑known component of the Chinese herbal medicine Huanglian (Coptis chinensis), and is capable of inhibiting the proliferation of multiple cancer cell lines. However, information available regarding the effect of berberine on prostate cancer cell growth is limited. In the present study, LnCaP and PC‑3 human prostate cancer cell lines were selected as in vitro models in order to assess the efficacy of berberine as an anticancer agent. A cell proliferation assay demonstrated that berberine inhibited cell growth in a dose‑and time‑dependent manner. Further investigation revealed berberine significantly accumulated inside cells that were in the G1 phase of the cell cycle and enhanced apoptosis. Western blot analysis demonstrated that berberine inhibited the expression of prostate‑specific antigen and the activation of epidermal growth factor receptor (EGFR), and it attenuated EGFR activation following EGF treatment in vitro. In conclusion, the results indicate that berberine inhibits the proliferation of prostate cancer cells through apoptosis and/or cell cycle arrest by inactivation of the EGFR signaling pathway. PMID: 25394789 [PubMed - as supplied by publisher] 3. Mini Rev Med Chem. 2014 Nov 7. [Epub ahead of print]

Alpha-Helical Cationic Anticancer Peptides: A Promising Candidate of Novel Anticancer Drugs.

Huang Y, Feng QI, Yan Q, Hao X, Chen Y(1). Author information:  (1)College of Life Sciences, Jilin University, Changchun, China. chen_yuxin@jlu.edu.cn. Cancer has become a great concern in public health. The harmful side effects and multidrug resistance of traditional chemotherapy prompt urgent needs for novel anticancer drugs or therapeutic approaches. Anticancer peptides (ACPs) have become promising molecules as new anticancer agents due to the unique mechanism and several extraordinary properties. Most α-helical ACPs target on cell membrane and the interactions between ACPs and cell membrane components are believed to be a key factor in the selective killing of cancer cells. In this review, we focus on the exploitation of the structure and function of α-helical ACPs, including the distinction of cancer cells and normal cells, the proposed anticancer mechanisms, and the influence of physicochemical parameters of α-helical ACPs on the biological activities and selectivity against cancer cells. In addition, the design and modification methods to optimize the cell selectivity of α-helical ACPs are also considered. Finally, the suitability of ACPs as cancer therapeutics is also discussed. 4. Eur J Pharmacol. 2014 Oct 5;740:584-95. doi: 10.1016/j.ejphar.2014.06.025. Epub 2014 Jun 26.

Targets and mechanisms of berberine, a natural drug with potential to treat cancer with special focus on breast cancer.

Jabbarzadeh Kaboli P(1), Rahmat A(2), Ismail P(3), Ling KH(4). Author information:  (1)Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia; Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia. Electronic address: pjabbarzadeh@gmail.com. (2)Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia. Electronic address: asmah@upm.edu.my. (3)Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia. Electronic address: patimah@upm.edu.my. (4)Department of Obstetrics and Gynecology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia; Genetics and Regenerative Medicine Research Centre, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM Serdang 43400, Selangor, Malaysia. Breast cancer is the most common cancer among women worldwide and novel therapeutic agents are needed to treat this disease. The plant-based alkaloid berberine has potential therapeutic applications for breast cancer, although a better understanding of the genes and cellular pathways regulated by this compound is needed to define the mechanism of its action in cancer treatment. In this review, the molecular targets of berberine in various cancers, particularly breast cancer, are discussed. Berberine was shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells. Some signaling pathways affected by berberine, including the MAP (mitogen-activated protein) kinase and Wnt/β-catenin pathways, are critical for reducing cellular migration and sensitivity to various growth factors. This review will discuss recent studies and consider the application of new prospective approaches based on microRNAs and other crucial regulators for use in future studies to define the action of berberine in cancer. The effects of berberine on cancer cell survival and proliferation are also outlined. 5. Mol Med Rep. 2014 Oct;10(4):1734-8. doi: 10.3892/mmr.2014.2405.

Berberine induces apoptosis and DNA damage in MG‑63 human osteosarcoma cells.

Zhu Y(1), Ma N(2), Li HX(3), Tian L(4), Ba YF(5), Hao B(6). Author information: (1)Department of Orthopedic Surgery, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China. (2)Department of Interventional Radiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. (3)Department of Pathology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China. (4)Department of Medicine, Zhengzhou Ninth People's Hospital, Zhengzhou, Henan 450014, P.R. China. (5)Department of Thoracic Surgery, The Affiliated Tumor Hospital of Zhengzhou University (Henan Tumor Hospital), Zhengzhou, Henan 450008, P.R. China. (6)Department of Urology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China. Berberine, an isoquinoline alkaloid extracted from the dry root of Coptidis Rhizoma, has been found to exhibit marked anticancer effects on a panel of established cancer cells. Among the human osteosarcoma lines treated, MG‑63 cells were found to be the most sensitive. The present study investigated the potential genotoxic effect of berberine on MG‑63 human osteosarcoma cells. The effect of berberine on cell viability was determined using a 3-(4,5-dimethylthiazol-2-yl)-2,5‑diphenyltetrazolium bromide assay and cell apoptosis was analyzed by flow cytometry and a DNA ladder assay. γH2AX focus formation was used to detect DNA damage in MG-63 cells. Berberine induced a significant increase in apoptosis in MG-63 cells in a concentration- and time-dependent manner, as determined by DNA fragmentation analysis and flow cytometry. Furthermore, berberine induced significant concentration- and time-dependent increases in DNA damage compared with that in the negative control. In conclusion, these observations indicated that berberine induced apoptosis and DNA damage in MG‑63 cells. Related Posts

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