The Complex Link between Apoptosis and Autophagy: a Promising New Role for RB

Delou, João Marcos de Azevedo; Biasoli, Deborah; Borges, Helena L.

doi:10.1590/0001-3765201620160127

Cited by 24 publications

(26 citation statements)

References 139 publications

(43 reference statements)

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“…The regulation of autophagy on cell death is 2-fold: mild autophagy protects cells from harmful conditions and promotes cell survival; severe or rapid autophagy can induce programmed cell death, known as autophagic cell death (autophagy-mediated cell death, ACD). However, the regulation of apoptosis on cell death is unidirectional, and the defect of apoptosis will lead to the occurrence of tumor cell death (36)(37)(38)(39). Aspp2 induced apoptosis protein expression in Aspp2-ad and combination groups, Bax and activation of caspase-3 expression increased greatly both in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 99%

Synergistic inhibitory effects on hepatocellular carcinoma with recombinant human adenovirus Aspp2 and oxaliplatin via p53-independent pathway in vitro and in vivo

Liu

Wang

et al. 2017

International Journal of Oncology

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The present study was designed to investigate the synergistic inhibitory effects on hepatocellular carcinoma with recombinant human adenovirus Aspp2 (Aspp2-ad) and oxaliplatin via p53-independent pathway in vitro and in vivo. After being treated with Aspp2-ad and/or oxaliplatin for 24-48 h, HepG2P53-/- and Hep3B cells showed a significant growth inhibition compared with vehicle control. Combination group showed a synergetic effect, the inhibitory rates were all above 80% at 48 h point in HepG2P53-/- and Hep3B cells. The apoptotic cell numbers of Aspp2-ad and/or oxaliplatin treatment groups were increased remarkably, especially for the combined therapy group in the liver cancer cells. The Hep3B xenograft experiment also showed similar inhibition of Aspp2-ad and/or oxaliplatin to the in vitro experiment. H&E results showed that combination group had the least mitotic indexes and the most necrosis. The immunohistochemistry results showed that PCNA, CD31 expression decreased greatly in treatment groups. These results suggested that Aspp2-ad might inhibit proliferation and vascular growth of hepatocarcinoma. Aspp2 induced apoptosis protein expression in Aspp2-ad and combination groups, the Aspp2, Bax and activation of caspase-3 expression increased greatly both in vitro and in vivo. But interestingly, the autophagy proteins showed different responses not only in HepG2P53-/- and Hep3B cells but also in vitro and in vivo. We found that Aspp2-ad downregulated the p-ERK, p-STAT3 expression, the synergistic effects were observed in combination group, while there was not response of mTOR to Aspp2-ad. In conclusion, Aspp2-ad, in P53-independent manner, regulated ERK and STAT3 signal moleculars to inhibit hepatocarcinoma in coordination with oxaliplatin by influencing the protein expression of proliferation, apoptosis, autophagy and vascular growth. Aspp2-ad has the potential to be developed in gene therapy for HCC, especially for P53 deletion or mutation in HCC.

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Section: Discussionmentioning

confidence: 99%

Synergistic inhibitory effects on hepatocellular carcinoma with recombinant human adenovirus Aspp2 and oxaliplatin via p53-independent pathway in vitro and in vivo

Liu

Wang

et al. 2017

International Journal of Oncology

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“…Furthermore, we observed that the NRK-52E cells were treated with curcumin showed a significant activation of protective autophagy and upregulated the level of Beclin 1 and the ratio of LC3II and LC3I. Previous study found that curcumin could protect cells against oxidative stress-induced damage through inhibiting apoptosis and inducing autophagy ( 20 ). Our findings also confirm this conclusion.…”

Section: Discussionmentioning

confidence: 74%

Curcumin suppresses AGEs induced apoptosis in tubular epithelial cells via protective autophagy

et al. 2017

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Renal tubular cell apoptosis and tubular dysfunction is an important process underlying diabetic nephropathy (DN). Understanding the mechanisms underlying renal tubular epithelial cell survival is important for the prevention of kidney damage associated with glucotoxicity. Curcumin has been demonstrated to possess potent anti-apoptotic properties. However, the roles of curcumin in renal epithelial cells are yet to be defined. The present study investigated advanced glycation or glycoxidation end-product (AGE)-induced toxicity in renal tubular epithelial cells via several complementary assays, including cell viability, cell apoptosis and cell autophagy in the NRK-52E rat kidney tubular epithelial cell line. The extent of apoptosis was significantly increased in the NRK-52E cells following treatment with AGEs. The results also indicated that curcumin reversed this effect by promoting autophagy through the phosphoinositide 3-kinase/AKT serine/threonine kinase signaling pathway. These conclusions suggested that curcumin exerts a renoprotective effect in the presence of AGEs, at least in part by activating autophagy in NRK-52E cells. Collectively, these findings indicate that curcumin not only exerts renoprotective effects, however may also act as a novel therapeutic strategy for the treatment of diabetic nephropathy.

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“…Research on pRb shows that it plays a fundamental role in cell cycle mechanisms ( 35 ). pRb is obtained when the Rb is phosphorylated by CDKs ( 36 ), then it is able to release E2F.…”

Section: Discussionmentioning

confidence: 99%

microRNA-3129 promotes cell proliferation in gastric cancer cell line SGC7901 via positive regulation of pRb

Yang¹,

Sheng²,

Pan³

et al. 2018

Braz J Med Biol Res

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Several microRNAs (miRNAs) have been reported as oncogenes or tumor suppressors in many cancers, including gastric cancer (GC). However, the role and molecular mechanism of miR-3129 in GC is largely unknown. We aimed to explore the function and the underlying molecular mechanism of miR-3129 in GC. Cancer tissues and corresponding adjacent tissues were collected from 50 patients with GC, and the expression of miR-3129 was detected by RT-qPCR. The expression of miR-3129 and pRb in human GC cell line SCG7091 was altered by transient transfection. Thereafter, MTT and flow cytometry assays were used to analyze cell viability and cell cycle. The expression of cyclin E, CDK2, CDK2 inhibitors (p16 and 21), and pRb were detected by RT-qPCR and western blot. A significant up-regulation of miR-3129 was observed in GC tissues compared to adjacent tissues. Overexpression of miR-3129 significantly improved cell viability after 4 days of post-transfection. Flow cytometry assay results showed that the miR-3129 overexpression arrested more SGC7901 cells at S phase. Moreover, overexpression of miR-3129 down-regulated the expression of CDK2 inhibitors while it up-regulated the expression levels of cyclin E, CDK2, and pRb. Interestingly, we found that pRb inhibition reversed the effect of miR-3129 inhibitor on cell proliferation in SGC7901 cells, increased cell viability, reduced cells at G0/1 phase, and modulated the expression of proliferation-related factors. Our results revealed that miR-3129 functioned as an oncogene through positive regulation of pRb and may prove to be a promising option for molecular therapy of GC.

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The Complex Link between Apoptosis and Autophagy: a Promising New Role for RB

Cited by 24 publications

References 139 publications

Synergistic inhibitory effects on hepatocellular carcinoma with recombinant human adenovirus Aspp2 and oxaliplatin via p53-independent pathway in vitro and in vivo

Synergistic inhibitory effects on hepatocellular carcinoma with recombinant human adenovirus Aspp2 and oxaliplatin via p53-independent pathway in vitro and in vivo

Curcumin suppresses AGEs induced apoptosis in tubular epithelial cells via protective autophagy

microRNA-3129 promotes cell proliferation in gastric cancer cell line SGC7901 via positive regulation of pRb

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