Imiquimod simultaneously induces autophagy and apoptosis in human basal cell carcinoma cells

Huang, Suming; Kt, Liu; Chang, Chia‐Che; Yj, Chen; Cy, Wu; Jj, Tsai; Wc, Lu; Yt, Wang; Cm, Liu; Shieh, Jeng-Jer

doi:10.1111/j.1365-2133.2010.09827.x

Cited by 52 publications

(50 citation statements)

References 38 publications

(87 reference statements)

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“…Previous studies have shown that inhibition of autophagy can aggravate apoptosis [27,28] and that inhibition of apoptosis can induce autophagy in A549 cells [47], suggesting the two processes are linked physiologically. To determine whether effects of naphthazarin on apoptosis and autophagy are independent, or are a consequence of one process affecting the other, we analyzed cells treated with naphthazarin in the presence of either apoptosis or autophagy inhibitors (zVAD-fmk or 3MA, respectively).…”

Section: Autophagy and Apoptosis Occur Independently Upon Naphthazarimentioning

confidence: 98%

The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells

et al. 2011

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Naphthazarin (DHNQ, 5,8-dihydroxy-l,4-naphthoquinone) is a naturally available 1,4-naphthoquinone derivatives. In this study, we focused on elucidating the cytotoxic mechanism of naphthazarin in A549 non-small cell lung carcinoma cells. Naphthazarin reduced the A549 cell viability considerably with an IC(50) of 16.4 ± 1.6 μM. Naphthazarin induced cell death in a dose- and time-dependent manner by activating apoptosis and autophagy pathways. Specifically, we found naphthazarin inhibited the PI3K/Akt cell survival signalling pathway, measured by p53 and caspase-3 activation, and PARP cleavage. It also resulted in an increase in the ratio of Bax/Bcl2 protein levels, indicating activation of the mitochondrial apoptotic pathway. Similarly naphthazarin triggered LC3II expression and induced autophagic flux in A549 cells. We demonstrated further that naphthazarin is a microtubule inhibitor in cell-free system and in A549 cells. Naphthazarin treatment depolymerized interphase microtubules and disorganised spindle microtubules and the majority of cells arrested at the G(2)/M transition. Together, these data suggest that naphthazarin, a microtubule depolymerizer which activates dual cell death machineries, could be a potential novel chemotherapeutic agent.

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Section: Autophagy and Apoptosis Occur Independently Upon Naphthazarimentioning

confidence: 98%

The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells

et al. 2011

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“…IMQ simultaneously induces autophagy and apoptosis in skin BCC cells [12]. Under metabolic stress, AMPK promotes autophagy by directly activating ULK1 through Ser 317, Ser 555 and Ser 777 phosphorylation [19].…”

Section: Imq-induced Autophagy Is Independent Of Ampkmentioning

confidence: 99%

“…Two major anti-tumoral mechanisms of IMQ, i.e., direct cancer cell death through the induction of apoptosis and autophagic cell death, have been reported. IMQ induces membrane-death receptor-independent apoptosis in various skin cancer cells [9,10] as well as autophagic cell death in Caco-2 colon cancer cells and BCC cell lines [11,12]. IMQ rapidly depletes Mcl-1 protein levels via translation inhibition in skin cancer cells, and Mcl-1 over-expression results in resistance to IMQ-induced apoptosis [13].…”

mentioning

confidence: 99%

Imiquimod-induced AMPK activation causes translation attenuation and apoptosis but not autophagy

Wang¹,

Huang²,

Kao³

et al. 2015

Journal of Dermatological Science

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“…First, imiquimod may induce programmed death of gastric cancer cells, such as autophagy and apoptosis. Accumulating evidence indicates that TLR7 activity is not restricted to the elicitation of innate and adaptive immune responses, but directly triggers programmed cell death in various types of cancer, such as melanoma and colon cancer (16,27). Second, TLR7 is selectively expressed in plasmacytoid dendritic cells (pDCs).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of TLR7 in gastric cancer tissues and the effects of TLR7 activation on gastric cancer cells

et al. 2016

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Abstract. The present study aimed to determine the expression of Toll-like receptor 7 (TLR7) in gastric cancer tissues and investigate the effects of its activation on gastric cancer cells. Patients with gastric cancer (n=30) and patients without gastric cancer (control; n=14) who underwent gastroscopy were enrolled in the study. Gastric cancer and cancer-adjacent tissues were obtained from the patients with gastric cancer, and normal gastric epithelial tissues were obtained from the control patients. The TLR7 mRNA and protein expressions in different tissues were investigated by reverse transcription-quantitative polymerase chain reaction, western blotting and immunohistochemistry. The present study also determined the effects of TLR7 activation by the agonist imiquimod on TLR7 protein expression, proinflammatory cytokine secretion and viability in SGC-7901 gastric cancer cells. The mRNA and protein expression levels of TLR7 were significantly downregulated in gastric cancer tissues compared with cancer-adjacent and normal gastric epithelial tissues (P<0.01). Imiquimod significantly increased TLR7 protein expression levels, and promoted the secretion of proinflammatory cytokines tumor necrosis factor-α and interleukin-6 in SGC-7901 cells. Furthermore, imiquimod inhibited the proliferation of SGC-7901 cells in a dose-and time-dependent manner. Thus, the present study identified that the expression of TLR7 was decreased in gastric cancer tissues, and TLR7 activation enhanced TLR7 expression, promoted the production of proinflammatory cytokines and inhibited the growth of gastric cancer cells.

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Imiquimod simultaneously induces autophagy and apoptosis in human basal cell carcinoma cells

Abstract: This study not only demonstrates that imiquimod can directly induce autophagy and apoptosis in BCC cells, but also shows the cooperation and coordination between these two processes to induce cell death.

Cited by 52 publications

References 38 publications

The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells

The microtubule depolymerizing agent naphthazarin induces both apoptosis and autophagy in A549 lung cancer cells

Imiquimod-induced AMPK activation causes translation attenuation and apoptosis but not autophagy

Decreased expression of TLR7 in gastric cancer tissues and the effects of TLR7 activation on gastric cancer cells

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