Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment

Cossu, Federica; Milani, Mario; Mastrangelo, Eloise; Lecis, Daniele

doi:10.1016/j.csbj.2019.01.009

Cited by 79 publications

(68 citation statements)

References 122 publications

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“…In some cases, signals transmit to effector caspase-3/7 via Bcl-2 families and cleaved caspase-9 through the mitochondria. This pathway also finally leads to cell death and is termed the mitochondria pathway [4,5]. Members of the Bcl-2 family are closely related to tumorigenesis, tumor progression, tumor metastasis, drug resistance, and prognosis.…”

Section: Introductionmentioning

confidence: 99%

Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway

Jin

Shi

Liu

et al. 2019

IJMS

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Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.

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Section: Introductionmentioning

confidence: 99%

Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway

Jin

Shi

Liu

et al. 2019

IJMS

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“…XIAP is a member of the “inhibitor of apoptosis” family, a group of proteins characterized by the presence of baculoviral IAP repeats, responsible for their inhibitory binding to caspases. XIAP in particular can bind both initiator and effector caspases (61).…”

Section: Discussionmentioning

confidence: 99%

Casein Kinase 1 Delta Regulates Cell Proliferation, Response to Chemotherapy and Migration in Human Ovarian Cancer Cells

et al. 2019

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Casein kinase 1 delta (CK1δ) has a tumor-promoting role in different cancers and it is genetically amplified in a portion of human epithelial ovarian cancer (EOC). CK1δ is involved in pleiotropic cellular functions such as cell proliferation, DNA damage, and migration. We specifically knocked down CK1δ by short hairpin RNA (shRNA) in human ovarian cancer cells and we performed proliferation, chemosensitivity, as well as in vitro and in vivo migration assays. CK1δ knocked-down cells displayed reduced proliferation capability both in vitro and in vivo. Nonetheless, these cells were sensitized to the first line chemotherapeutic agent carboplatin (CPT), and this observation could be associated to reduced expression levels of p21(Cip1/Waf1), involved in DNA damage response, and the anti-apoptotic X-linked inhibitor of apoptosis protein (XIAP). Moreover, CK1δ knocked-down cells were affected in their migratory and lung homing capability, even if in opposite ways, i.e., IGROV1, SKOV3 and MES-OV lost, while OVCAR3 gained motility potential. The results suggest CK1δ as a potential exploitable target for pharmacological EOC treatment, but they also advise further investigation of its role in cell migration.

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“…4A). Nevertheless, several other residues that have been reported as being important for the correct conformation of the chelating fold and caspase binding are not conserved in A. pisum BIR domains (37,38). Ap-Deterin-1 has a unique BIR domain, where the histidine and third cysteine of the Zn 2+ binding motif are separated by 10 amino acids instead of 6.…”

Section: A Pisum Caspases Are Expressed and Contain The Functional Dmentioning

confidence: 99%

Evolutionary novelty in the apoptotic pathway of aphids

Lopes

Parisot

Gaget

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Apoptosis, a conserved form of programmed cell death, shows interspecies differences that may reflect evolutionary diversification and adaptation, a notion that remains largely untested. Among insects, the most speciose animal group, the apoptotic pathway has only been fully characterized inDrosophila melanogaster, and apoptosis-related proteins have been studied in a few other dipteran and lepidopteran species. Here, we studied the apoptotic pathway in the aphidAcyrthosiphon pisum, an insect pest belonging to the Hemiptera, an earlier-diverging and distantly related order. We combined phylogenetic analyses and conserved domain identification to annotate the apoptotic pathway inA. pisumand found low caspase diversity and a large expansion of its inhibitory part, with 28 inhibitors of apoptosis (IAPs). We analyzed the spatiotemporal expression of a selected set of pea aphid IAPs and showed that they are differentially expressed in different life stages and tissues, suggesting functional diversification. Five IAPs are specifically induced in bacteriocytes, the specialized cells housing symbiotic bacteria, during their cell death. We demonstrated the antiapoptotic role of these five IAPs using heterologous expression in a tractable in vivo model, theDrosophila melanogasterdeveloping eye. Interestingly, IAPs with the strongest antiapoptotic potential contain two BIR and two RING domains, a domain association that has not been observed in any other species. We finally analyzed all available aphid genomes and found that they all show large IAP expansion, with new combinations of protein domains, suggestive of evolutionarily novel aphid-specific functions.

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Targeting the BIR Domains of Inhibitor of Apoptosis (IAP) Proteins in Cancer Treatment

Cited by 79 publications

References 122 publications

Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway

Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway

Casein Kinase 1 Delta Regulates Cell Proliferation, Response to Chemotherapy and Migration in Human Ovarian Cancer Cells

Evolutionary novelty in the apoptotic pathway of aphids

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