Anoikis is adherent cells (anchorage-dependent cell) death of an important mechanism for normal cell growth and reproduction only through adherence to , so as to avoid unattached epidermal cells spread around . Anoikis abnormal tumor cells , epithelial cells occurs - mesenchymal transition (epithelial-mesenchymal transition), leading to tumor metastasis . This cell -mediated and neighboring cells (neighboring cell) or the extracellular matrix (extracellular matrix) is a known interaction between integrins (integrin) of the cell surface receptor, which is α, β subunits form heterodimer , has so far revealed 18 α -subunit β subunits and 9 , according to a combination of more than 20 different integrins , tumor cells and normal cells of different subtypes of integrins , integrin inhibiting inducible anoikis . In the research integrin inhibitors Cilengitide (αυβ3 and αυβ5 inhibitors , III clinical ), ATN-161 (αυβ3 and α5β1 inhibitors , II clinical ) .
2 autophagic cell death (autophagic cell death)
Autophagy has a dual role , on the one hand can lead to tumor cell death , it can also protect tumor cells. In the main study autophagy inhibitor chloroquine (chloroquine) and hydroxychloroquine (hydroxychloroquine), by interfering with tumor cell autophagy , enhanced chemotherapy, radiation effects. Autophagy inducer letter is mainly for PI3K/Akt/mTOR pathways, such as mTOR inhibitor sirolimus (Sirolimus), for Seamus Division (Temsirolimus), everolimus (Everolimus). The other two Bcl-2/Bcl-XL/Mcl-1 inhibitors gossypol (Gossypol, AT-101, I / II clinical ) and Obatoclax (GX15-070, II clinical ) .
3 necrotizing apoptosis / necrosis and orderly (necroptosis or regulated necrosis)
Cell Death Nomenclature Committee (Nomenclature Committee on Cell Death) will be defined as necrotizing dependent apoptosis , necrosis RIP1 or RIP3 , RIP1 kinase inhibitor Necrostatin-1 ( for neurodegenerative diseases and myocardial infarction ) can stop this process. Shikonin (Shikonin) was the first to be discovered necrotizing apoptosis-inducing agent, anthracyclines , vinca alkaloids, taxol , epipodophyllotoxin resistant cell lines such as valid explanation for the resistance to wither the death of the cancer cells are not necessarily anti- necrotic death.
4 mitotic catastrophe (mitotic catastrophe)
Mitotic catastrophe mitosis due to interference , with different degrees of division stop , eventually leading to cell death or aging. Spindle kinesin (kinesin spindle protein, KSP) in spindle formation plays an important or so, has become a selective effect a new target dividing cells . Unlike first generation of microtubule inhibitors such as taxol , vinblastine , KSP inhibitors only on the cell division , proliferation of non- mature tissue had no effect. KSP inhibitors entering clinical studies have Ispinesib (SB-715992, II clinical ), AZD4877 (I / II clinical ) . ATM/ATR-CHK1/CHK2 inhibitors also induced mitotic catastrophe , a new generation of selective CHK1 inhibitor AZD7762 (I clinical ), PF477736 (I clinical aborted ), SCH900776 (II clinical ) and so on.
5 Class apoptosis (paraptosis)
Class of apoptosis and apoptosis has distinct morphological features of apoptosis occurs category , the cell volume becomes large, the electron microscope, you can see a large number of mitochondria and endoplasmic reticulum formed cytoplasmic vacuoles . Class apoptotic caspase-9 is driven variants , Apaf-1 and is not dependent shear independent PARP , caspase and Bcl-xL inhibitors do not block the class of apoptosis . There is no special class of apoptosis inducing compounds into clinical studies , bromocriptine (Bromocriptine), tocotrienols (Tocotrienol), ginseng saponins (Ginsenoside), honokiol (Honokiol), scallops toxin (Yessotoxin) may induce apoptotic cell type .
6. PARP-1 -dependent death (parthanatos)
Parthanatos relates to a DNA damage response enzyme PARP (poly (ADP-ribose) polymerase, PARP-1 in which more than 90% ) , inhibition of PARP can prevent DNA repair , and enhance the efficacy of radiotherapy . PARP inhibitors have a lot in research , such as Veliparib (ABT-888, II clinical ), Rucaparib (AG014699, II clinical ), Iniparib (II clinical ) .
7. Methuosis
Originally discovered as a giant endocytosis (macropinocytosis) disorders caused by necrosis -like cell death , followed by glioblastoma found in a similar form of cell death , and this pro-apoptotic cancer cells are highly resistant to the drug . Now that is not dependent methuosis clathrin endosomes (endosome) changes trigger , and ultimately the formation of large vacuoles , causing cell rupture. The compounds induced methuosis chalcone derivatives MOMIPP and podophyllotoxin derivatives F14512.
8 of lysosomal membrane permeability (lysosomal membrane permeabilization) and oncotic (oncosis)
Lysosomal disorder causes oncosis , therefore both classified as a class . The basic characteristics of apoptotic cell shrinkage and cracking , while the opposite Oncosis , cell swelling and then cytoplasmic condensation. Caused a sharp decline in intracellular ATP Oncosis intracellular energy supply shortage will lead to cell membrane ion pump damage, eventually leading to a series of changes by oncosis . Oncosis is an important feature of early mitochondrial permeability transition pore (mitochondrial permeablity transition pore, mPTP) opening , which does not require the release of cytochrome c. Lysosomal membrane permeability of the causes lysosomal hydrolases (lysosomal hydrolase) into the cytoplasm , leading to cell damage. The most studied is Kahalalide F (II clinical ) , which acts on the lysosomes, induces oncosis . Another clinical study drugs into Mott DM gadolinium (Motexafin gadolinium, II clinical ) , which can induce lysosomal membrane permeabilized , for the treatment of brain tumors. Other investigational drugs belonging to this class there Fenway A amine (Fenretinide, 4HPR), Syrah new U.S. (Siramesine), Biphosphinic Palladacycle Complex, artesunate (Artesunate), Australia eggplant side base (Solamargine).
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