Caspase‐mediated programmed cell death pathways as potential therapeutic targets in cancer

Wen, Xin; Lin, Zhongxiao; Liu, B.; Wei, Yuquan

doi:10.1111/j.1365-2184.2012.00814.x

Cited by 110 publications

(97 citation statements)

References 59 publications

(55 reference statements)

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“…This initiates the apoptosis cascade, finally resulting in apoptosis. The activation of the caspase family is an important prerequisite for apoptosis since the caspase family activates apoptosis-related proteases when apoptosis occurs (32,33). We analyzed changes in the activation of caspases-9, -8 and -3 following treatment with embelin and found a significant increase in the activation of caspase-9, -8 and -3 with the occurrence of brain glioma apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway

Wang

Zhang

et al. 2013

Oncology Reports

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Abstract. Brain glioma is the most common malignant intracranial tumor and has become the focus of research on diseases of the central nervous system due to its high incidence and poor prognosis. As a small-molecule inhibitor of X-linked inhibitor of apoptosis protein (XIAP), embelin has the ability to specifically inhibit XIAP to control and regulate the apoptosis of various types of tumor cells. However, to date, the mechanism of action for this effect is not well understood. The aim of this study was to investigate the role that the mitochondrial pathway plays in embelin-induced brain glioma cell apoptosis and the effect of embelin on the cell cycle. Brain glioma cells were treated with different doses of embelin. The MTT method

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Section: Discussionmentioning

confidence: 99%

Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway

Wang

Zhang

et al. 2013

Oncology Reports

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“…However, in this contact, the S1 caspase pocket, which is responsible for caspase substrate selectivity, remains free. Studies have shown that the linker region between the BIR1 and BIR2 domain in the XIAP protein has no function in caspase 3 and 7 inhibition as it was previously thought (7,13,17,18).…”

Section: Mechanism Of Caspases Inhibitionmentioning

confidence: 99%

“…If the heterodimer of caspase 9 is formed, there is no possibility of forming a supportive sequential element (L2 loop) which is a characteristic of homodimerisation and is thereby inactive. It is interesting that cIAP1 and cIAP2 cannot inhibit caspase 9 by preventing homodimerisation as XIAP can, because they do not contain the special sequence of four amino acids (12,13,18).…”

Section: Mechanism Of Caspases Inhibitionmentioning

confidence: 99%

Apoptosis Regulation by Inhibitors of Programmed Cell Death

Marković¹,

Đorđević²

2013

Journal of Medical Biochemistry

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Summary: Apoptosis is a form of cell death which is important in many physiological processes. Four apoptotic mechanisms have been identified but two have been well examined: the intrinsic and the extrinsic mechanism. Due to many pro/antiapoptotic factors, these processes take place on a physiologically useful level. In cases of apoptosis dysregu lation, illnesses occur such as neurodegenerative diseases combined with an increased level of cell death or cancerogenesis associated with uncontrolled cell proliferation. Apoptosis can be triggered by the activation of the first caspase in a series and stopped by its deactivation, which represents a new challenge: determining the »point of no return«. Besides the antiapoptotic proteins (Bcl 2, Bcl XL), a family of proteins called the Inhibitors of Apoptosis Proteins (IAPs) play a key role in the regulation of apoptosis. Members of the IAP family are: cIAP1, cIAP2, XIAP, Survivin, Livin and TsIAP. Domain BIR is the most important in the IAP structure since it determines their specificity for caspases. The interaction of IAPs with caspases is complex and not completely understood, however, IAPs are considered to be important target proteins in the therapy of tumor and autoimmune diseases. Keywords: IAP protein (apoptosis), caspases, programmed cell death type IKratak sadr`aj: Apoptoza predstavlja oblik }elijske smrti i va`na je u mnogim fiziolo{kim procesima. Postojẽ etiri oblika }elijske smrti a dva su dobro prou~ena: unutra{nji i spolja{nji. Zahvaljuju}i mnogim pro/antiapoptoti~kim faktorima, ovaj proces se odvija na fiziolo{ki korisnom nivou. U slu~aju disregulacije apoptoze nastaju bolesti kao {to su neurodegenerativna oboljenja udru`ena sa povi{enim nivoom }elijske smrti ili karcinogeneza udru`ena sa nekontrolisanom }elijskom proliferacijom. Apoptozu mo`e po krenuti aktivacija prve kaspaze u nizu i prekinuti njena deaktivacija, {to predstavlja novi izazov: odrediti »ta~ku bez povratka«. Pored antiapoptoti~nih proteina (Bcl 2, Bcl XL), familija proteina nazvanih inhibitori apoptoze (eng. Inhibitors of Apoptosis Proteins, IAPs) igra klju~nu ulogu u procesu regulacije. Pripadnici familije IAP su: cIAP1, cIAP2, XIAP, survivin, livin i TsIAP. Domen BIR je naj zna~ajniji u strukturi IAP budu}i da odre|uje specifi~nost ka kaspazama. Interakcija IAP sa kaspazama je kompleksna i nedovoljno istra`ena, me|utim, smatra se da IAPs pred stavljaju va`ne ciljne proteine u terapiji tumora i auto imunih oboljenja.

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“…2A, treatment of cells with cordycepin or TRAIL alone induced a slight loss of MMP in Hep3B cells; however, combined treatment with cordycepin and TRAIL caused a significant concentration-dependent induction of MMP loss. In particular, the anti-apoptotic Bcl-2 family molecules such as Bcl-2 and Bcl-xL, and IAP family members protect some tumor cell lines from TRAIL-induced apoptosis (22)(23)(24); therefore, we investigated the expression levels of members belonging to the Bcl-2 and IAP family. As shown in Fig.…”

Section: Effects Of Cordycepin and Trail Co-treatment On The Expressimentioning

confidence: 99%

Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway

et al. 2013

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Abstract. Resistance to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis has been reported in various cancer cells. Cordycepin, a specific polyadenylation inhibitor, is the main functional component in Cordyceps militaris, which possesses many pharmacological activities including antitumor and anti-inflammation. In the present study, we demonstrated that treatment of cordycepin sensitized TRAIL-resistant Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis as evidenced by formation of apoptotic bodies, chromatin condensation and accumulation of cells in the sub-G1 phase. The induction of apoptosis following co-treatment with cordycepin and TRAIL in Hep3B cells appeared to be correlated with modulation of Bcl-2 family protein expression and activation of the caspase cascade, which resulted in the cleavage of poly(ADP-ribose) polymerase and β-catenin. In addition, cordycepin treatment also inhibited activation of c-Jun N-terminal kinase (JNK).Pretreatment with SP600125, a JNK inhibitor, resulted in a significantly increased sub-G1 population and caspase activity in cordycepin plus TRAIL-mediated apoptosis. Taken together, these results indicate that JNK acts as a key regulator of apoptosis in response to combined treatment with cordycepin and TRAIL in human hepatocellular carcinoma Hep3B cells.

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Caspase‐mediated programmed cell death pathways as potential therapeutic targets in cancer

Cited by 110 publications

References 59 publications

Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway

Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway

Apoptosis Regulation by Inhibitors of Programmed Cell Death

Cordycepin increases sensitivity of Hep3B human hepatocellular carcinoma cells to TRAIL-mediated apoptosis by inactivating the JNK signaling pathway

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