Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins

Lee, Sung-Jun; Noh, Hyo-Jeong; Sung, Eon‐Gi; Song, In‐Hwan; Kim, Joo-Young; Kwon, Taeg Kyu; Lee, Tae-Jin

doi:10.3892/ijo.2010.878

Cited by 31 publications

(15 citation statements)

References 32 publications

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“…These observations are in line with previous reports showing that BBR itself promotes the activation of procaspase 9 and mitochondria deregulation, typically observed in the intrinsic subroutine of apoptosis [19], although in some experimental systems BBR proved to activate the extrinsic pathway [46, 47]. The proapoptotic effect of BBR on cancer cells was reported to be associated with the modulation of JNK/p38-redox/ROS process, HER2/PI3K/AKT signaling, p53 -regulated factors and NF- κ B, AP-1, Wnt, and COX-2 proteins [3, 7, 22, 40, 42].…”

Section: Resultssupporting

confidence: 92%

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

Ortiz

Tillhon

Parks

et al. 2014

BioMed Research International

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The pharmacological use of the plant alkaloid berberine is based on its antibacterial and anti-inflammatory properties; recently, anticancer activity has been attributed to this compound. To exploit this interesting feature, we synthesized three berberine derivatives, namely, NAX012, NAX014, and NAX018, and we tested their effects on two human colon carcinoma cell lines, that is, HCT116 and SW613-B3, which are characterized by wt and mutated p53, respectively. We observed that cell proliferation is more affected by cell treatment with the derivatives than with the lead compound; moreover, the derivatives proved to induce cell cycle arrest and cell death through apoptosis, thus suggesting that they could be promising anticancer drugs. Finally, we detected typical signs of autophagy in cells treated with berberine derivatives.

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Section: Resultssupporting

confidence: 92%

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

Ortiz

Tillhon

Parks

et al. 2014

BioMed Research International

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“…Hypoxia-generated ROS increases Na, K-ATPase degradation via the ubiquitin-conjugating system [25]. ROS was shown to trigger Mcl-1 degradation through the proteasomal pathway [26, 27]. Here, we show that ROS promotes the degradation of Mcl-1 and survivin in the hypoxic tumor cells.…”

Section: Discussionmentioning

confidence: 54%

Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia

et al. 2016

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Sirt3, a mitochondrial deacetylase, participates in the regulation of multiple cellular processes through its effect on protein acetylation. The objective of this study was to explore the role of Sirt3 in the mitochondrial autophagy (mitophagy), a process of the specific autophagic elimination of damaged mitochondria. We found that silencing of Sirt3 expression in human glioma cells by RNA interference blunted the hypoxia-induced the localization of LC3 on the mitochondria, and the degradation of mitochondria. These results suggest an important involvement of this protein deacetylase in the induction of mitophagy in cancer cells subjected to hypoxia. Further, we demonstrated that Sirt3 activated the hypoxia-induced mitophagy by increasing the interaction of VDAC1 with Parkin. In the cells subjected to hypoxia, inhibition of Sirt3-mediated mitophagy further decreased the mitochondrial membrane potential, and increased the accumulation of ROS that triggers the degradation of anti-apoptotic proteins Mcl-1 and survivin through the proteasomal pathway. Silencing of Sirt3 expression also promoted apoptosis, and enhanced the sensitivity of cancer cells to hypoxia. The regulatory role of Sirt3 in autophagy and apoptosis was also observed in human breast cancer cells. The results of the current study reveal Sirt3 as a novel regulator coupling mitophagy and apoptosis, two important cellular processes that determine cellular survival and death.

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“…cFLIP is the major protein that prevents caspase-8 from activation by death receptors through binding to FADD and/or caspase-8 and TRAIL receptor DR5 in a ligand-dependent and -independent manner and forms an apoptosis inhibitory complex (AIC), then prevents death-inducing signaling complex (DISC) formation and subsequently suppress the activation of caspase cascade (46)(47)(48)(49)(50)(51)(52)(53). Mcl1 is an antiapoptotic protein involved in death receptor mediated pathway crosslink to mitochondrial mediated pathway by interacting with truncated Bid (tBid) and then strongly inhibits tBid-induced cytochrome c release in mitochondrial mediated apoptosis pathway (54)(55)(56)(57). Downregulation of cFLIP and Mcl1 expression sensitizes TRAIL-induced apoptosis in various TRAIL refractory cancers.…”

Section: Discussionmentioning

confidence: 99%

Goniothalamin enhances TRAIL-induced apoptosis in colorectal cancer cells through DR5 upregulation and cFLIP downregulation

Sophonnithiprasert

Nilwarangkoon

Nakamura

et al. 2015

International Journal of Oncology

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Abstract. The combination of TNF-related apoptosis-inducing ligand (TRAIL) and bioactive compound to enhance apoptosis in TRAIL-resistant cancer is one of cancer treatment strategies. TRAIL possesses the unique capacity to selectively induce apoptosis in cancer cells both in vitro and in vivo with little effect on normal cells. Recent studies have reported that there are many TRAIL-resistant cancers. Thus, bioactive compounds that enhance cytotoxicity of TRAIL would be potential candidates for cancer therapeutic application. This study evaluated the cytotoxic and apoptosis induction upon combined treatment of TRAIL and goniothalamin, the natural styryl-lactone compound extracted from plant Goniothalamus spp., in LoVo cells. The results showed that a combination of goniothalamin and TRAIL enhanced caspase-dependent apoptosis induction in LoVo cells via both death receptor-and mitochondrial-mediated apoptosis pathways. In addition, goniothalamin enhanced TRAIL-induced apoptosis through increased death receptor DR5 expression and decreased anti-apoptotic regulator cFLIP. Interestingly, goniothalamin increased translocation of DR5 to cell surface and consequently contributed to the enhancement of TRAIL-induced apoptosis. In conclusion, this is the first report showing the combined treatment of goniothalamin and TRAIL was able to effectively enhance TRAIL-mediated apoptosis induction in TRAIL-refractory colorectal cancer, LoVo cells. Therefore, this study may offer a strategic cancer treatment against TRAIL-resistant cancers.

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Berberine sensitizes TRAIL-induced apoptosis through proteasome-mediated downregulation of c-FLIP and Mcl-1 proteins

Cited by 31 publications

References 32 publications

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

Multiple Effects of Berberine Derivatives on Colon Cancer Cells

Sirt3-mediated mitophagy protects tumor cells against apoptosis under hypoxia

Goniothalamin enhances TRAIL-induced apoptosis in colorectal cancer cells through DR5 upregulation and cFLIP downregulation

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