Ivermectin induces cell cycle arrest and caspase-dependent apoptosis in human urothelial carcinoma cells

Tung, Chun‐Liang; Chao, Wen-Ying; Li, Yi-Zhen; Shen, Cheng‐Huang; Zhao, Peiwen; Chen, Shu-Hsin; Wu, Tzu-Yun; Lee, Ying‐Ray

doi:10.7150/ijms.76623

Cited by 7 publications

(3 citation statements)

References 26 publications

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“…According to our findings, the ERK1/2 inhibitor PD98059 decreased the inflammatory cytokine levels in LPS-induced A549 cells with SIRT6 knockdown. ERK1/2 is a pro-apoptotic signaling molecule activated in response to DNA damage 42 , 43 . Our study shows that apoptosis exacerbated by SIRT6 knockdown in ARDS could be reversed by inhibiting the ERK1/2 pathway.…”

Section: Discussionmentioning

confidence: 99%

SIRT6 ameliorates LPS-induced apoptosis and tight junction injury in ARDS through the ERK1/2 pathway and autophagy

Liu¹,

Wang²,

Gong³

et al. 2023

Int. J. Med. Sci.

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Sirtuin6 (SIRT6) has been demonstrated to be involved in a range of physiological processes and diseases, while its role in acute respiratory distress syndrome (ARDS) remains unclear. Therefore, this study focused on the role and underlying mechanism of SIRT6 in ARDS with the aim of identifying potential therapeutic targets. In this study, we found that SIRT6 was significantly decreased in lipopolysaccharide (LPS)-induced A549 cells and a murine model. In vitro overexpression of SIRT6 restored the expression of tight junction proteins (ZO-1 and occludin) and alleviated cell apoptosis and inflammation, while knockdown of SIRT6 aggravated the loss of tight junction proteins (ZO-1 and occludin) and promoted cell apoptosis and inflammation in LPS-induced A549 cells. Furthermore, the overexpression of SIRT6 enhanced autophagy and inhibited the ERK1/2 pathway, while the knockdown of SIRT6 inhibited autophagy and activated the ERK1/2 pathway. The autophagy activator rapamycin and the ERK1/2 inhibitor PD98059 rescued the effects of SIRT6 knockdown on tight junction proteins, apoptosis, and inflammation. Mechanistically, SIRT6 deacetylated histone 3 at Lys9 to negatively regulate the ERK1/2 pathway. In vivo , the SIRT6-specific inhibitor OSS_128167 also significantly accelerated LPS-induced loss of tight junction proteins, lung inflammation, and apoptosis. Meanwhile, the SIRT6-specific inhibitor OSS_128167 also activated the ERK1/2 pathway and inhibited lung autophagy. These results suggested that SIRT6 could ameliorate the loss of tight junction proteins, inflammation, and apoptosis in LPS-induced ARDS by inhibiting the ERK1/ 2 pathway and enhancing autophagy, indicating that SIRT6 plays a beneficial role in ARDS and might be a potential therapeutic target for ARDS.

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Section: Discussionmentioning

confidence: 99%

SIRT6 ameliorates LPS-induced apoptosis and tight junction injury in ARDS through the ERK1/2 pathway and autophagy

Liu¹,

Wang²,

Gong³

et al. 2023

Int. J. Med. Sci.

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show abstract

“…The inhibition was due to the downregulation of the protein Akt, essential for cell growth and survival. In addition, IVM induced apoptosis in the bladder cancer cells by activating caspase-3 and caspase-7, two proteins involved in the programmed cell death pathway 32 . These findings suggest that IVM could be a potential therapeutic option for bladder cancer.…”

Section: Urinary System Cancermentioning

confidence: 99%

“…It is characterized by distinct morphological and biochemical features, including chromatin condensation, DNA fragmentation, and the formation of apoptotic bodies 40 . IVM has been shown to induce apoptosis in various tumor cells, including Hela cells, through both extrinsic and intrinsic pathways 32,41,42 .…”

Section: Apoptosismentioning

confidence: 99%

Anticancer Potential of Ivermectin: Mechanisms of Action and Therapeutic Implications

Lotfalizadeh,

Gharib,

Hajjafari

et al. 2022

J Lab Anim. Res

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Ivermectin is a well-known antiparasitic drug in the macrolide class with a 16-membered ring. It has been used for treating various parasitic diseases, including onchocerciasis, lymphatic filariasis, and strongyloidiasis. The present study aimed to review the mechanisms of action and therapeutic implications of Ivermectin as an anticancer agent. It has been used for over three decades, and its safety has been well-established in humans A growing body of evidence suggests that ivermectin has anticancer properties, making it an attractive candidate for treating various types of cancer. The reason is that ivermectin targets multiple signaling pathways, including the Wnt/β-catenin, PI3K/Akt/mTOR, and STAT3 pathways, to inhibit cancer cell proliferation and induce apoptosis. Inhibition of these pathways by ivermectin leads to suppression of cancer cell growth. Additionally, ivermectin has been shown to induce autophagy, which can lead to programmed cell death in cancer cells. One of the significant advantages of ivermectin as an anticancer drug is its safety profile. Furthermore, it is easily available and affordable, making it a promising alternative to conventional chemotherapy for various types of cancer, including breast, lung, and colon cancer. However, further research is needed to evaluate its clinical effectiveness in humans. Clinical trials are underway to investigate ivermectin's safety and efficacy in cancer treatment. In conclusion, the safety profile and low cost of ivermectin as an anticancer drug have turned it into a feasible alternative to conventional chemotherapy, which needs more investigation.

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Common hotspots of cancer chemotherapy

Ademikanra

Oyewole

Olayiwola

2023

GENOME INSTAB. DIS.

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Ivermectin induces cell cycle arrest and caspase-dependent apoptosis in human urothelial carcinoma cells

Cited by 7 publications

References 26 publications

SIRT6 ameliorates LPS-induced apoptosis and tight junction injury in ARDS through the ERK1/2 pathway and autophagy

SIRT6 ameliorates LPS-induced apoptosis and tight junction injury in ARDS through the ERK1/2 pathway and autophagy

Anticancer Potential of Ivermectin: Mechanisms of Action and Therapeutic Implications

Common hotspots of cancer chemotherapy

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