Increasing the therapeutic efficacy of docetaxel for cutaneous squamous cell carcinoma through the combined inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy

Wright, TD; McKee, Christopher S.; Birch-Machin, MA; Ellis, Robert; Armstrong, Jane L.; Lovat, Penny E.

doi:10.1111/ced.12138

Cited by 21 publications

(16 citation statements)

References 10 publications

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“…Many studies argue that autophagy is implicated in cancer cells resistance to chemotherapy and thus autophagy inhibition could improve the anticancer outcome by resensitizing cancer cells to chemotherapy 17,18,59 . Nevertheless, other reports suggest that autophagy enhances the effect of chemotherapy and radiotherapy inducing cell death 60,61 .…”

Section: Discussionmentioning

confidence: 97%

Dual role of autophagy on docetaxel-sensitivity in prostate cancer cells

et al. 2018

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Prostate cancer (PC) is one of the leading causes of death in males. Available treatments often lead to the appearance of chemoresistant foci and metastases, with mechanisms still partially unknown. Within tumour mass, autophagy may promote cell survival by enhancing cancer cells tolerability to different cell stresses, like hypoxia, starvation or those triggered by chemotherapic agents. Because of its connection with the apoptotic pathways, autophagy has been differentially implicated, either as prodeath or prosurvival factor, in the appearance of more aggressive tumours. Here, in three PC cells (LNCaP, PC3, and DU145), we tested how different autophagy inducers modulate docetaxel-induced apoptosis. We selected the mTOR-independent disaccharide trehalose and the mTOR-dependent macrolide lactone rapamycin autophagy inducers. In castration-resistant PC (CRPC) PC3 cells, trehalose specifically prevented intrinsic apoptosis in docetaxel-treated cells. Trehalose reduced the release of cytochrome c triggered by docetaxel and the formation of aberrant mitochondria, possibly by enhancing the turnover of damaged mitochondria via autophagy (mitophagy). In fact, trehalose increased LC3 and p62 expression, LC3-II and p62 (p62 bodies) accumulation and the induction of LC3 puncta. In docetaxel-treated cells, trehalose, but not rapamycin, determined a perinuclear mitochondrial aggregation (mito-aggresomes), and mitochondria specifically colocalized with LC3 and p62-positive autophagosomes. In PC3 cells, rapamycin retained its ability to activate autophagy without evidences of mitophagy even in presence of docetaxel. Interestingly, these results were replicated in LNCaP cells, whereas trehalose and rapamycin did not modify the response to docetaxel in the ATG5-deficient (autophagy resistant) DU145 cells. Therefore, autophagy is involved to alter the response to chemotherapy in combination therapies and the response may be influenced by the different autophagic pathways utilized and by the type of cancer cells.

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Section: Discussionmentioning

confidence: 97%

Dual role of autophagy on docetaxel-sensitivity in prostate cancer cells

et al. 2018

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“…Previous studies have reported that increased basal autophagy contributes to resistance to MTIs, although the mechanisms are not clear [34]. Also, it has been reported that increased basal autophagy contributes to resistance to other anticancer drugs, such as the DNAdamaging agent cisplatin, which has a cancer-killing action that depends at least partially on SAC function [22,[35][36][37]].…”

Section: Discussionmentioning

confidence: 99%

SIRT2 knockdown increases basal autophagy and prevents postslippage death by abnormally prolonging the mitotic arrest that is induced by microtubule inhibitors

Inoue

Nakayama

et al. 2014

The FEBS Journal

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Mitotic catastrophe, a form of cell death that occurs during mitosis and after mitotic slippage to a tetraploid state, plays important roles in the efficacy of cancer cell killing by microtubule inhibitors (MTIs). Prolonged mitotic arrest by the spindle assembly checkpoint is a well-known requirement for mitotic catastrophe, and thus for conferring sensitivity to MTIs. We previously reported that turning off spindle assembly checkpoint activation after a defined period of time is another requirement for efficient postslippage death from a tetraploid state, and we identified SIRT2, a member of the sirtuin protein family, as a regulator of this process. Here, we investigated whether SIRT2 regulates basal autophagy and whether, in that case, autophagy regulation by SIRT2 is required for postslippage death, by analogy with previous insights into SIRT1 functions in autophagy. We show, by combined knockdown of autophagy genes and SIRT2, that SIRT2 serves this function at least partially by suppressing basal autophagy levels. Notably, increased autophagy induced by rapamycin and mild starvation caused mitotic arrest for an abnormally long period of time in the presence of MTIs, and this was followed by delayed postslippage death, which was also observed in cells with SIRT2 knockdown. These results underscore a causal association among increased autophagy levels, mitotic arrest for an abnormally long period of time after exposure to MTIs, and resistance to MTIs. Although autophagy acts as a tumor suppressor mechanism, this study highlights its negative aspects, as increased autophagy may cause mitotic catastrophe malfunction. Thus, SIRT2 offers a novel target for tumor therapy.

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“…In this line, an increased expression of the autophagy marker LC3 has been demonstrated in patients with SCC, which was associated with disease progression and prognosis of cancer [ 300 ]. Interestingly, an in vitro study showed that the inhibition of both Akt signaling and autophagy by the lysosomal inhibitor chloroquine enhanced the susceptibility of metastatic SCC cells to docetaxel-induced apoptosis [ 301 ].…”

Section: Inflammation and Skin Cancermentioning

confidence: 99%

Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

et al. 2015

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The risk of onset of cancer is influenced by poorly controlled chronic inflammatory processes. Inflammatory diseases related to cancer development include inflammatory bowel disease, which can lead to colon cancer, or actinic keratosis, associated with chronic exposure to ultraviolet light, which can progress to squamous cell carcinoma. Chronic inflammatory states expose these patients to a number of signals with tumorigenic effects, including nuclear factor kappa B (NF-κB) and mitogen-activated protein kinases (MAPK) activation, pro-inflammatory cytokines and prostaglandins release and ROS production. In addition, the participation of inflammasomes, autophagy and sirtuins has been demonstrated in pathological processes such as inflammation and cancer. Chemoprevention consists in the use of drugs, vitamins, or nutritional supplements to reduce the risk of developing or having a recurrence of cancer. Numerous in vitro and animal studies have established the potential colon and skin cancer chemopreventive properties of substances from marine environment, including microalgae species and their products (carotenoids, fatty acids, glycolipids, polysaccharides and proteins). This review summarizes the main mechanisms of actions of these compounds in the chemoprevention of these cancers. These actions include suppression of cell proliferation, induction of apoptosis, stimulation of antimetastatic and antiangiogenic responses and increased antioxidant and anti-inflammatory activity.

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Increasing the therapeutic efficacy of docetaxel for cutaneous squamous cell carcinoma through the combined inhibition of phosphatidylinositol 3-kinase/AKT signalling and autophagy

Cited by 21 publications

References 10 publications

Dual role of autophagy on docetaxel-sensitivity in prostate cancer cells

Dual role of autophagy on docetaxel-sensitivity in prostate cancer cells

SIRT2 knockdown increases basal autophagy and prevents postslippage death by abnormally prolonging the mitotic arrest that is induced by microtubule inhibitors

Bioactive Compounds Isolated from Microalgae in Chronic Inflammation and Cancer

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