Olive oil induces apoptosis in some cancer cells due to phenolic compounds like oleuropein. Signaling pathway switch in breast cancer cancer cell. Diallyl disulfide dads retards the growth of breast cancer cells in vitro and in vivo through apoptosis induction. Dr glynns groups current area of interest in breast cancer is to further investigate nos2 in triple negative breast cancer and also to investigate potential links with hervk and investigating the functions of hervk proteins and their mrnas. Delanzomib induced cell death and demonstrated synergism with dox in all tested breast cancer cell lines. Apoptosis in pathologic conditions dna damage due to radiation, chemotherapy. Oct 31, 2016 impaired apoptosis is one of the hallmarks of cancer. In this study, we found that cambogin inhibited breast cancer cell proliferation and induced cell apoptosis in vitro. Understanding the apoptotic signaling pathways in breast. Adenoviral transduction of testin gene into breast and. Drugs whose primary action involves modulation of ubiquitin. Cannabidiol induces programmed cell death in breast cancer.
The p53 pathway in breast cancers lacking p53 mutations. Cacf induced apoptosis in mcf7 cells as marked by cell size shrinkage, deformed cytoskeletal structure and dna fragmentation. The mechanism of apoptosis is complex and involves many pathways. Phang laboratory of nutritional and molecular regulation, national cancer institutefrederick cancer research and development center, nih. Arecentstudyreportsthat cbd inhibits breast cancer growth 11 and downregulates id1, a regulator of metastasis in breast cancer cell authors affiliation. Effects of estrogen on apoptotic pathways in human breast cancer cell line mcf7 thomas t. Pdf apoptosis is an ordered and orchestrated cellular process that occurs in physiological and. In order to study the anticancer effects and cellular apoptosis pathways induced by daidzein. The explosion of interest in apoptosis amongst cancer biologists has been underpinned by the hope that a mechanistic understanding of cell death will inform our understanding of tumour drug resistance. Pdf oleuropein induces apoptosis via the p53 pathway in breast cancer cells zeinab hassan and nada merghani academia. Apoptotic signaling pathway and resistance to apoptosis in. Silencing bmi1 in mcf breast cancer cells reported to downregulate the. The extrinsic pathway of apoptosis is activated at the cell surface when a specific ligand.
Clearly, there are many ways a cancer cell can avoid apoptosis. Effects of estrogen on apoptotic pathways in human breast. Astragalus membranaceus, extract, breast cancer, apoptosis, pi3k, akt background breast cancer is the most threatening health problem for women worldwide in incidence and mortality. Chemotherapy for breast cancer often includes drugs such as doxorubicin that induce dna damage and subsequently the p53mediated apoptotic response. Apoptosis markers in breast cancer include circulating soluble fasl, granzyme b, and cytochrome c that increase following chemotherapy. In the present study, we showed that nnmt was selectively expressed in some breast cancer cell lines, downregulation of nnmt expression in bcap37 and mdamb231 cell lines by nnmt shrna significantly.
In this study, we showed that cacf inhibited growth of mcf7 human breast cancer cells. We aimed to investigate the cytotoxic effects of nimbolide, a limonoid present in leaves and flowers of the neem tree azadirachta indica on human breast cancer cells. Apoptosis markers in breast cancer therapy request pdf. Plac8 contributes to cell proliferation and suppresses cell apoptosis in bc by acti. In a recent study, extract from the blue green algae spirulina platensis, combined with selenium an. The current study sought to investigate the prognostic potential of caspase3 and 8 in breast cancer, as well as the prognostic value of combinatorial caspase and. Further, metastasis was inhibited through downregulation of. Overexpression and activation of this receptor are commonly detected in colorectal cancer, and several lines of evidence indicate that overexpression and activation of erk mapk play an important part in progression of this cancer.
In the barplot depicting the proportion of cancer samples with altered pathways 19 pathways are listed in the xaxis the yaxis represents the percentage of samples altered in a given pathway stratified by subtype red for basal, purple for erbb2, blue for luminal a, cyan for luminal b, and green for normallike. Plca8 suppresses breast cancer apoptosis by activating the. Bcl2 may also play a role in nonhematologic tumors, and inappropriate expression has been observed in solid tumors such as prostate, breast, and small cell and nonsmall cell lung cancers. Efficient treatment against malignant tumours is therefore necessary in cancer management. Bcl2 is an antiapoptotic protein, while bax is a proapoptotic protein.
In conclusion, curcumin inhibited the proliferation of breast cancer cells and induced g2m phase cell cycle arrest and apoptosis, which may be associated with the decrease of cdc25 and cdc2 and increase of p21 protein levels, as well as inhibition of the phosphorylation of aktmtor and induction of the mitochondrial apoptotic pathway. Defects in apoptosis signalling contribute to resistance of tumors. Cambogin is a polycyclic polyprenylated acylphoroglucinol ppap from the garcinia genus, which has been used traditionally for cancer treatment across southeastern asia. Downregulation of nicotinamide nmethyltransferase induces. In summary, the results suggest that our compounds promote apoptosis of breast cancer cell lines via p53dependent and independent pathways. Thus, more effective drugs and new regimens for the therapy of tnbc are urgently needed. Curcumin inhibits proliferation and promotes apoptosis of. The results of our study provide new insights into an oncogenic role of plac8 and reveal a novel plac8 pi3kaktnfb path. Shwachmanbodiandiamond syndrome protein desensitizes breast cancer cells to apoptosis in sti.
The involvement of possible signaling pathways and the roles of quercetin in the apoptosis of other cancer cells remain unde ned. Induction of apoptosis in breast cancer cells mdamb231 by. Lncrna nonhsat141924 promotes paclitaxel chemotherapy. Prostate carcinoma mutated p53, decreased bcl2 28, 47 breast carcinoma decreased bcl2 60 apoptosis, cancer and cancer therapy 9 therapy directed at apoptosis the role of apoptosis in the progression of cancer and in both chemo and radiotherapy of malignancy will influence the development of future treatment regimens. In this study a431 cells, derived from epidermoid carcinoma, are used as a model to.
Simultaneous inhibition of cellcycle, proliferation. Understanding apoptosis and apoptotic pathways targeted cancer. Apoptosis of breast cancer cells northwestern engineering. Research open access silencing cdk4 radiosensitizes breast cancer cells by promoting apoptosis katie r hagen1, xiangbin zeng1, miyoung lee1, shannon tucker kahn1, mary kathryn harrison pitner1, sandra s zaky1, yuan liu3, ruth m oregan2, xingming deng1 and harold i saavedra1 abstract background. The survival rates of cells with lncrnanonhsat141924 overexpression or knockdown and the blank control cells as measured using mtt assay under treatment of ptx with concentration. Apoptosis vs necrosis necrosis is the uncontrolled pathological cell death. Curcumin was also found to promote apoptosis of breast cancer cells. The mapk signalling pathways and colorectal cancer the. Baicalein induces apoptosis and autophagy of breast cancer. For example, if a drug inhibits bcl2 family proteins, it will initiate apoptosis in cancer cells. A summary of some of the more promising strategies for modulating the activity of apoptosis genes and proteins for cancer therapy is provided below, according to the apoptosis pathways they affect. The understanding of pathways involved in breast cancer pathogenesis contributes to the identification of new targeted therapeutic agents as well and can also be utilized in diagnosis and prognosis.
Pdf oleuropein induces apoptosis via the p53 pathway in. Necrosis is the uncontrolled pathological cell death. The hippo pathway transducers yap1tead induce acquired. It induces apoptosis when interacted with its ligand cd95l fasl. The p53 pathway in breast cancer breast cancer research. These two types of nuclear hormone receptors form homo or heterodimers upon ligand binding and translocate into the cell nucleus for transcriptional regulation, which is the main function of ers.
Daidzein induces mcf7 breast cancer cell apoptosis via the. The role of the ubiquitinationproteasome pathway in breast. Induction of apoptosis by icariside ii through extrinsic and intrinsic signaling pathways in human breast cancer mcf7 cells. Breast cancer is one of the most common causes of cancer death to women worldwide.
Apoptosis markers in breast cancer therapy sciencedirect. Cancer progression is favoured by dna damage and in most cases a consequent disruption of the apoptotic pathway, thus leading to. Apoptotic molecular advances in breast cancer management. Understanding apoptosis pathways for cancer therapeutics. Resveratrolinduced apoptosis in human breast cancer cells is mediated primarily through the caspase3dependent pathway. Lncrna nonhsat141924 promotes ptxresistance through pcrebbcl2 apoptosis signaling pathway in breast cancer. Apoptosis pathways in cancer and cancer therapy springerlink. Although oleuropein has anticancer activity, the underlying mechanisms of action remain unknown. Jun 11, 2019 triplenegative breast cancer tnbc is the most aggressive subtype of breast cancer with poor prognosis, and its treatment remains a challenge due to few targeted medicines and high risk of relapse, metastasis, and drug resistance. Highdose berberine directly induced apoptosis on drugresistant breast cancer by activating the ampkp53 pathway. Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from centratherum anthelminticum l. Role of stat3 signaling pathway in breast cancer cell. Cell death in viral infections that induce apoptosis such as hiv and adenovirus or by the host immune response such as hepatitis. However, cancer cells are resistant to cd95induced apoptosis because of the changes in death domain dd of cd95 procaspase8 and cflip.
Activation of apoptosis pathways is a key mechanism by which cytotoxic drugs kill tumor cells. Intrinsic apoptotic pathway activation increases response to anti. Disease pathways and cancer exploration genentech aims to advance the potential of combined pathway modulation in oncology. The optimal care pathways are based on a revision of the original patient management frameworks department of health 2007a which had, for the first time, attempted to map the cancer pathway in an easily understandable form.
Antiapoptotic bcl2 family proteins enhance breast tumor cell survival, often promoting resistance to targeted therapies, including endocrine. Feb 28, 2020 it has been reported earlier that stat3 can upregulate cyclin d1, cmyc, and bcl2 to suppress the apoptosis of breast cancer cells, indicating a potential involvement of stat3 in cell cycle and survival. Through intensive research in both cancer immunity and tumor targets, genentech aspires to make fundamental scientific discoveries that will provide a comprehensive, personalized approach in the fight against cancer. Nicotinamide nmethyltransferase nnmt has been found involved in cell proliferation of several malignancies. Quercetin a natural polyphenolic compound induced apoptosis in many human cancer cells, including mcf7 human breast cancer cells chou et al. These data suggest that downregulation of nnmt induces apoptosis via the mitochondriamediated pathway in breast cancer cells.
Moreover, stat3 activated by il6jak2 pathway can inhibit baxbcl2related caspasedependent apoptosis. Classical il6 jakstat3 pathways can activate the transcription of cyclin d1, cmyc, bcl2 and bax to promote the proliferation and inhibit the apoptosis of breast cancer. Shwachmanbodiandiamond syndrome protein desensitizes. Breast cancer is a complex disease that results from the dysregulation of signaling networks caused by the genetic and epigenetic alterations in cells. Jan 29, 2004 activation of apoptosis pathways is a key mechanism by which cytotoxic drugs kill tumor cells. Estrogen receptor prevents p53dependent apoptosis in. Unlike normal cells, cancer cells are characterized by inhibited apoptosis, uncontrolled growth and proliferation, and metastasis.
In the bc cell line mdamb231, cellular proliferation was inhibited via downregulation of the expression of the cell cycle regulator cyclin d and nf b. Galangin induces apoptosis in mcf7 human breast cancer cells through mitochondrial pathway and phosphatidylinositol 3kinaseakt inhibition article pdf available in pharmacology 10212. The novel proteasome inhibitor delanzomib sensitizes. In addition to antiestrogens in estrogen receptor erpositive breast. Essential molecules of the p53, mapk, and apoptosis signaling pathways were analyzed by western blotting. Cells were treated with molecular iodine at various concentrations to measure proliferation and cell death. Ongoing research at the apoptosis research centre in the area of breast cancers includes dr sharon glynn. Ampelopsininduced autophagy protects breast cancer cells. Baicalein, a widely used chinese herbal medicine, has shown anticancer effects on many types of human cancer.
The discovery of molecular markers associated with various breast cancer subtypes. Twentyfive percent of primary breast tumor samples as well as the breast cancer cell line t47d and the uterine sarcoma cell line messa were negative or displayed low levels of tes. However, the functional role of nnmt in breast cancer has not been elucidated. The united kingdom has the highest age standardised incidence and mortality from breast cancer in the world. Request pdf apoptotic signaling pathway and resistance to apoptosis in breast cancer stem cells a major challenge in the treatment of human breast cancer is the development of resistant. One key barrier in use of these apoptosis markers in breast cancer therapy is the lack of highquality database of healthy individuals, breast cancer patients and breast cancer patients after chemotherapy at multiple time points, analyzed retrospectively and prospectively, with longterm clinical data. Jun 27, 20 altered kegg pathways in breast cancers. Trpc3 regulates the proliferation and apoptosis resistance of triple negative breast cancer cells through the trpc3rasa4mapk pathway by yan wang 1, yanxiang qi 1, zenghua qi 1 and sukying tsang 1,2,3,4. Research open access silencing cdk4 radiosensitizes. Ilamycins are a kind of cyclic peptides and produced by streptomyces.
Cd95 fas is a complex integral protein that can be expressed in many cells. The role of hippo signal pathway in breast cancer metastasis changran wei,1 ying wang,2 xiangqi li1 1department of breast surgery, affiliated hospital of taishan medical university, taian, shandong province, china. Breast cancer pinkhien t, maiuthed a, chamni s, et al. The molecular mechanisms involved in the apoptotic activity exerted by nimbolide. Epigallocatechin3gallate egcg could suppress cancer growth and induce apoptosis in many types of cancer cells. These include the stat pathway and downstream components including cytokines and suppressors of. Diallyl disulfide dads retards the growth of breast. Epigallocatechin3gallate inhibits the growth and increases. Thyroid cancer is the most common type of endocrine malignancy and the incidence rate is rapidly increasing worldwide. We used the human mcf7 breast cancer cell line as a model and examined the apoptosis by hoechstpropidium iodide staining fluorescence imaging and flow cytometry. Unfortunately, there is a paucity of information in the. Pdf two natural alkaloids synergistically induce apoptosis in.
Clpp regulates breast cancer cell proliferation, invasion and apoptosis by modulating the srcpi3kakt signaling pathway juan luo 1, beilei zeng 1, chunfang tao. In contrast with apoptosis, cleanup of cell debris by phagocytes of the immune system is generally more difficult. Dim induced apoptosis and inhibited angiogenesis by suppressing the activity of the aktnfb signal ing pathway. Characterizing more precisely the manner by which cbd kills breast cancer cells will help define the optimal applications of cbd as a cancer therapeutic.
Pdf galangin induces apoptosis in mcf7 human breast. Induction of apoptosis by icariside ii through extrinsic and intrinsic signaling pathways in human breast cancer mcf7 cells chaoqing huang,1 xiaoguang chen,2. Antrodia cinnamomea extract inhibits the proliferation of tamoxifenresistant breast cancer cells through apoptosis and skp2micrornas pathway. Aberrations in apoptotic pathways are central to tumorigenesis, tumor progression, and overall tumor growth and regression in response to chemotherapy. Cancer is one of the leading causes of mortality worldwide and is a serious threat to human health and the quality of life of patients.
While drugs can target and restore the apoptotic pathway, cancer cells can acquire new mutations and become resistant. Chung yeng looi, aditya arya, foo kit cheah, bushra muharram, kok hoong leong, khalit mohamad, won fen wong, nitika rai, mohd rais mustafa. Trpc3 regulates the proliferation and apoptosis resistance of. Also immunotherapy of tumors requires an apoptosis sensitive phenotype of target cells. Ampelopsininduced autophagy protects breast cancer cells from apoptosis through aktmtor pathway via endoplasmic reticulum stress yong zhou, xinyu liang, hui chang, furong shu, ying wu, ting zhang, yujie fu, qianyong zhang, jundong. Signaling from the membrane yekaterina poloz, ryan j. Caspase3 and 8 are key regulators of the apoptotic response and have been shown to interact with the calpain family, a group of cysteine proteases, during tumorigenesis. Echinacoside inhibits breast cancer cells by suppressing. In this chapter, we discuss current anticancer strategies that are targeted on the apoptosis pathway in breast cancer management. Bishydroquinone renieramycin m induces apoptosis of human lung cancer cells through a mitochondriadependent pathway. Apoptosis is increased in ductal carcinoma in situ and invasive breast cancer. A framework for druginduced apoptosis can now be described in which a balance exists between intrinsic and extrinsic survival signals and druginduced death signals. From these results, we conclude that the inactivation of nf.
Disease pathways and cancer exploration biooncology. Introduction breast cancer is one of the most common causes of cancer related death in women, which accounts for one in four cancer related deaths in the united states 1. Induction of apoptosis in human breast cancer cells via. The role of hippo signal pathway in breast cancer metastasis.
Pdf induction of apoptosis in human breast cancer cells. Jun 23, 2001 breast cancer is the commonest malignancy in women and comprises 18% of all cancers in women. In order to understand breast cancer, it is necessary to understand the normal anatomy of the female breast 3, 20. Pdf resveratrolinduced apoptosis in human breast cancer. In summary, this work showed that lowdose berberine could enhance dox sensitivity on drugresistant breast cancer in vivo and in vitro through the ampkhif1. Berberine enhances chemosensitivity and induces apoptosis. Apoptosis is the cells natural mechanism for programed cell death. Clpp regulates breast cancer cell proliferation, invasion. However, the mechanism of action of egcg on the growth of human thyroid carcinoma cells has not been fully illuminated. After tes restoration by ad tes transduction, t47d and messa cell lines underwent apoptosis. Jul 24, 2003 from these results, we conclude that the inactivation of nf. Targeting apoptosis pathways in cancer and perspectives with.
The breast cancer study focused on two common breast cancer subtypes using wellestablished breast cancer cell lines, mcf7 a luminal a subtype and mdamb231 a triplenegative subtype. There are many causes of necrosis including injury, infection, cancer, infarction, toxins and inflammation. Cancer is a disease characterized by a very little apoptosis, ie, genetically programmed cell death. This pathway has been validated as a target for antineoplastic therapy using both in vitro and preclinical models of human malignancies, and is influenced as part of the mechanism of action of certain chemotherapeutic agents. Furthermore, apoptosis and stat3 signaling pathwayassociated protein levels. In cancer, the apoptotic pathway is typically inhibited through. Pdf breast cancer has become a worldwide threat, and.
In conclusion, our data show that genistein inhibits the growth of breast cancer cells, regulates the expression of apoptosis related genes, and induces apoptosis in mdamb231 breast cancer cells. Studies of apoptosis in breast cancer pubmed central pmc. B by genistein in mdamb231 breast cancer cells is partly mediated via akt pathway, which could be useful for rational design of. Induction of apoptosis by icariside ii through extrinsic. Apoptosis cancer steps examples pathway mechanism apoptosis. In addition, osthole, via binding to stat3 protein, is found to suppress stat3 activity and inhibit breast cancer cells apoptosis, whereas another stat3 inhibitor, stattic, is found to promote the baxbcl2mediated apoptosis in breast cancer and to increase the therapeutic effects of doxorubicin. I3c was shown to inhibit bone metastasis of mdamb231 breast cancer cells in a scid mouse model 21. Apoptosis, cancer and cancer therapy sciencedirect. Activation of apoptosis signalling following treatment with cytotoxic drugs has been shown to lead to activation of the mitochondrial intrinsic. Accumulation of misfolded proteins leads to er stress which ends with apoptosis. Cambogin induced the activation of the caspaseindependent mitochondrial apoptotic pathway, as. Ilamycin c induces apoptosis and inhibits migration and. Although the structure of p53 has been extensively studied, the absolute frequency of mutations in breast cancer is significantly lower than that in many other common cancers.
Extract from astragalus membranaceus inhibit breast cancer. The mapk pathways are located downstream of many growthfactor receptors, including that for epidermal growth factor. Cambogin induces caspaseindependent apoptosis through the. Induction of apoptosis by icariside ii through extrinsic and. The ubiquitinproteasome pathway is responsible for most eukaryotic intracellular protein degradation. Alternatively, one can envision directly activating agonists of apoptosis in cancer cells. Epoxyazadiradione suppresses breast tumor growth through mitochondrial depolarization and caspasedependent apoptosis by targeting pi3kakt pathway dhiraj kumar1, saikat haldar2, mahadeo gorain1, santosh kumar3, fayaj a.