Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells

Wei, Ming-Feng; Chen, Min-Wei; Chen, Ke-Cheng; Lou, Pei‐Jen; Lin, Sheng-Wei; Hung, Shih‐Chieh; Hsiao, Michael; Yao, Ching Fa; Shieh, Ming‐Jium

doi:10.4161/auto.28679

Cited by 169 publications

(144 citation statements)

References 64 publications

(59 reference statements)

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“…Downregulation of HSP70 increased PDT sensitivity and mediated PDT-induced apoptosis. Wei et al reported that autophagy is associated with PDT resistance in colorectal cancer stem-like cells (30). Autophagy and apoptosis may be triggered by common signals, resulting in combined autophagy and apoptosis.…”

Section: Hsp70 Plays a Fundamental Role In Protecting Cells Against Pdtmentioning

confidence: 99%

Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells

et al. 2016

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Abstract. We previously reported that photodynamic therapy (PDT) induces cell death in head and neck cancer through both autophagy and apoptosis. Regulation of cell death by autophagy and apoptosis is important to enhance the effects of PDT. Autophagy maintains a balance between cell death and PDT resistance. Downregulation of heat shock protein 27 (HSP27) induces PDT resistance in head and neck cancer cells. Furthermore, HSP70 regulates apoptosis during oxidative stress. However, the role of HSPs in PDT-induced cell death through autophagy and apoptosis is unclear. Therefore, in the present study, we investigated the effects of HSP27 and HSP70 on PDT-induced cell death of oral cancer cells through autophagy and apoptosis. Cancer cells were treated with hematoporphyrin at varying doses, followed by irradiation at 635 nm with an energy density of 5 mW/cm 2 . We determined the changes in HSP expression by determining the levels of PARP-1 and LC3II in PDT-resistant cells. Furthermore, we assessed cell death signaling after downregulating HSPs by transfecting specific siRNAs. We observed that PDT decreased HSP27 expression but increased HSP70 expression in the head and neck cancer cells. Treatment of cells with LC3II and PARP-1 inhibitors resulted in upregulation of HSP70 and HSP27 expression, respectively. Downregulation of HSP27 and HSP70 induced cell death and PDT resistance through autophagy and apoptosis. Moreover, downregulation of HSP27 in PDT-resistant cells resulted in enhanced survival. These results indicate that the regulation of HSP27 and HSP70 plays a principal role in increasing the effects of PDT by inducing autophagic and apoptotic cell death.

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Section: Hsp70 Plays a Fundamental Role In Protecting Cells Against Pdtmentioning

confidence: 99%

Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells

et al. 2016

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“…Autophagy activation was observed in colon cancer stem cells by analysis of the expression of the intestinespecific transcription factor Cdx1, which plays a crucial role in chemoresistance to paclitaxel [106] . Similarly, autophagy increased resistance to photodynamic therapyinduced apoptosis in CRC stemlike cells [139] . However, this report did not address whether the protective autophagy that was induced in cancer stem cells was due to a drug mediated response to stress or to the inherent ability of cancer stem cells to maintain a high threshold for autophagy.…”

Section: Autophagy Drugs In Crcmentioning

confidence: 99%

Autophagy in colorectal cancer: An important switch from physiology to pathology

Burada

Nicoli

Ciurea

et al. 2015

WJGO

137

131

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Colorectal cancer (CRC) remains a leading cause of cancer death in both men and women worldwide. Among the factors and mechanisms that are involved in the multifactorial etiology of CRC, autophagy is an important transformational switch that occurs when a cell shifts from normal to malignant. In recent years, multiple hypotheses have been considered regarding the autophagy mechanisms that are involved in cancer. The currently accepted hypothesis is that autophagy has dual and contradictory roles in carcinogenesis, but the precise mechanisms leading to autophagy in cancer are not yet fully defined and seem to be context dependent. Autophagy is a surveillance mechanism used by normal cells that protects them from the transformation to malignancy by removing damaged organelles and aggregated proteins and by reducing reactive oxygen species, mitochondrial abnormalities and DNA damage. However, autophagy also supports tumor formation by promoting access to nutrients that are critical to the metabolism and growth of tumor cells and by inhibiting cellular death and increasing drug resistance. Autophagy studies in CRC have focused on several molecules, mainly microtubule-associated protein 1 light chain 3, beclin 1, and autophagy related 5, with conflicting results. Beneficial effects were observed for some agents that modulate autophagy in CRC either alone or, more often, in combination with other agents. More extensive studies are needed in the future to clarify the roles of Core tip: This review describes the role of autophagy in cancer, focusing on the involvement of autophagy in colorectal cancer (CRC). Initially, we describe the steps and components of autophagy, and we then further highlight the dual role of autophagy in cancer, where it can potentially act as both a promoter and an inhibitor during the transformation from normal to malignant cell. In particular, we emphasize the major autophagy genes involved in CRC pathogenesis along with autophagymodulating agents and their modes of action in the context of CRC therapy. TOPIC HIGHLIGHT

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“…It has been reported that autophagy increases the resistance of colorectal cancer stem-like cells to photodynamic therapy-induced apoptosis (1,27,28). Similarly, cisplatin-activated autophagy, involving the activation of ATG7, has been indicated to increase liver cancer cell resistance to cisplatin (29).…”

Section: Discussionmentioning

confidence: 99%

Resveratrol induces autophagic apoptosis via the lysosomal cathepsin D pathway in human drug‑resistant K562/ADM leukemia cells

et al. 2018

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Abstract. The aim of the present study was to investigate the crosstalk between resveratrol (Res)-induced autophagy and apoptosis, and the molecular pathway by which autophagy leads to apoptotic death in drug-resistant K562/ADM leukemia cells. The viability of K562/ADM cells was determined using the MTT assay. The formation of autophagic vacuoles was detected using transmission electron microscopy and monodansylcadaverine (MDC) staining. Cell apoptosis was evaluated using flow cytometry. The expression of apoptosis-or autophagy-associated proteins was measured using western blotting. The results indicated that treatment with Res inhibited cell viability in a concentration-dependent manner. Furthermore, the numbers of MDC-positive fluorescent points, autophagic vacuoles and autolysosome-engulfed cytoplasmic materials were markedly increased in Res-treated K562/ADM cells compared with untreated cells, as determined using fluorescence microscopy and transmission electron microscopy. Res-induced apoptosis was associated with increased cleaved caspase-3 and B-cell lymphoma 2 associated X protein, and decreased B-cell lymphoma 2 (Bcl-2) protein expression levels when compared with the control (P<0.05). However, the proportion of apoptotic cells decreased from 69.6 to 41.0% (40 µmol/l Res) and from 77.3 to 58.8% (80 µmol/l Res) following pre-treatment with the autophagy inhibitor 3-methyladenine (P<0.01). The protein expression levels of microtubule-associated protein 1A/1B-light chain 3 and beclin 1, two markers of autophagy, were upregulated in Res-treated cells compared with the control (P<0.05). In addition, lysosomal cathepsin D (Cath D) release increased during Res-induced autophagy and apoptosis (P<0.05). The present results demonstrated that Res-induced apoptosis of K562/ADM cells was autophagy-dependent and the released Cath D may trigger caspase-dependent cell death through the Bcl-2 family of proteins. Furthermore, the present data indicate that to enhancement of the autophagy-cathepsin-apoptosis pathway may be an effective approach for overcoming anticancer drug resistance.

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Autophagy promotes resistance to photodynamic therapy-induced apoptosis selectively in colorectal cancer stem-like cells

Cited by 169 publications

References 64 publications

Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells

Effects of HSP27 downregulation on PDT resistance through PDT-induced autophagy in head and neck cancer cells

Autophagy in colorectal cancer: An important switch from physiology to pathology

Resveratrol induces autophagic apoptosis via the lysosomal cathepsin D pathway in human drug‑resistant K562/ADM leukemia cells

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