Cytoprotective autophagy induction by withaferin A in prostate cancer cells involves GABARAPL1

Hahm, Eun‐Ryeong; Singh, Shivendra V.

doi:10.1002/mc.23240

Cited by 14 publications

(9 citation statements)

References 30 publications

(45 reference statements)

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“…Total RNA was extracted from FoxQ1 overexpressing SUM159 and MCF‐7 cells and corresponding EV cells ( n = 3 for each) using the RNeasy® Mini kit (Qiagen) following the instructions provided by the manufacturer. Other details of the PCR array were essentially the same as described previously 21 . The data was analyzed using the web‐based software provided by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

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Forkhead Box Q1 is a novel regulator of autophagy in breast cancer cells

Kim

Hahm

Singh

2023

Molecular Carcinogenesis

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Forkhead Box Q1 (FoxQ1) transcription factor is overexpressed in luminal‐type and basal‐type human breast cancers when compared to normal mammary tissue. This transcription factor is best known for its role in promotion of breast cancer stem‐like cells and epithelial to mesenchymal transition. The present study documents a novel function of FoxQ1 in breast cancer cells. Overexpression of FoxQ1 in basal‐like SUM159 cells and luminal‐type MCF‐7 cells resulted in increased conversion of microtubule‐associated protein light chain 3 beta‐I (LC3B‐I) to LC3B‐II, which is a hallmark of autophagy. Autophagy induction by FoxQ1 overexpression was confirmed by visualization of LC3B puncta as well as by transmission electron microscopy. Expression profiling for genes implicated in autophagy regulation revealed upregulation of many genes, including ATG4B, ATG16L1, CTSS, CXCR4 and so forth but downregulation of BCL2L1, DRAM1, TNF, ULK2 and so forth by FoxQ1 overexpression in SUM159 cells. Western blot analysis confirmed upregulation of ATG4B and CXCR4 proteins by FoxQ1 overexpression in both SUM159 and MCF‐7 cells. Chromatin immunoprecipitation assay revealed recruitment of FoxQ1 at the promoter of ATG4B. Pharmacological inhibition of ATG4B using S130 significantly increased apoptosis induction by DOX in empty vector transfected as well as FoxQ1 overexpressing SUM159 and MCF‐7 cells but this effect was statistically significantly lowered by FoxQ1 overexpression indicating the protective role of FoxQ1 on apoptosis. Treatment of SUM159 cells with S130 and DOX enhanced LC3B‐II level in both empty vector transfected cells and FoxQ1 overexpressing SUM159 cells but not in FoxQ1 overexpressing MCF‐7 cells. In conclusion, FoxQ1 is a novel regulator of autophagy.

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Section: Methodsmentioning

confidence: 99%

“…Other details of the PCR array were essentially the same as described previously. 21 The data was analyzed using the web-based software provided by the manufacturer. The threshold cycles were calculated and the genes with values above 35 were considered undetected.…”

Section: Human Autophagy Rt 2 Profiler™ Polymerase Chain Reaction (Pc...mentioning

confidence: 99%

Forkhead Box Q1 is a novel regulator of autophagy in breast cancer cells

Kim

Hahm

Singh

2023

Molecular Carcinogenesis

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“…Hitherto, several withanolides, including withaferin A, 3‐azido withaferin A, physapubescin B, physapubenolide, and physagulide P, were found to exhibit active cytostatic autophagy (Ma et al, 2017; Rah et al, 2015; Xu et al, 2017; Yu et al, 2017), whereas our group previously found that the cytoprotective autophagy was initiated by physalin A (He, Zang, Feng, Wang, et al, 2013). Intriguingly, withaferin A is quite distinctive since the autophagy induced by withaferin A was cytoprotective in prostate cancer cells(Hahm & Singh, 2020), and in breast cancer cells (Muniraj et al, 2019).…”

Section: Anticancer Mechanisms Of Withanolidesmentioning

confidence: 99%

Withanolides: Promising candidates for cancer therapy

Zhang,

Yuan,

Cao

et al. 2024

Phytotherapy Research

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Natural products have played a significant role throughout history in the prevention and treatment of numerous diseases, particularly cancers. As a natural product primarily derived from various medicinal plants in the Withania genus, withanolides have been shown in several studies to exhibit potential activities in cancer treatment. Consequently, understanding the molecular mechanism of withanolides could herald the discovery of new anticancer agents. Withanolides have been studied widely, especially in the last 20 years, and attracted the attention of numerous researchers. Currently, over 1200 withanolides have been classified, with approximately a quarter of them having been reported in the literature to be able to modulate the survival and death of cancer cells through multiple avenues. To what extent, though, has the anticancer effects of these compounds been studied? How far are they from being developed into clinical drugs? What are their potential, characteristic features, and challenges? In this review, we elaborate on the current knowledge of natural compounds belonging to this class and provide an overview of their natural sources, anticancer activity, mechanism of action, molecular targets, and implications for anticancer drug research. In addition, direct targets and clinical research to guide the design and implementation of future preclinical and clinical studies to accelerate the application of withanolides have been highlighted.

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“…Inhibition of AKT signaling. [ 48–58 ] Renal carcinoma Caki Inducing endoplasmic reticulum stress (ERS) mediates apoptosis. [ 59 , 60 ] Colorectal cancer WS480, HT-29, HCT-116, RKO, SW-480, SW-620, Caco-2 Inducing ERS-mediated autophagy and apoptosis, G2/M arrest.…”

Section: The Anti-tumor Efficacy Of Wa Against Various Cancersmentioning

confidence: 99%

Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms

Xing,

Su,

et al. 2023

DDDT

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Cancer, as the leading cause of death worldwide, poses a serious threat to human health, making the development of effective tumor treatments a significant challenge. Natural products continue to serve as crucial resources for drug discovery. Among them, Withaferin A (WA), the most active phytocompound extracted from the renowned dietary supplement Withania somnifera (L.) Dunal, exhibits remarkable anti-tumor efficacy. In this manuscript, we aim to comprehensively summarize the pharmacological characteristics of WA as a potential anti-tumor drug candidate, with the objective of contributing to its further development and the discovery of prospective drugs. Through an extensive review of literature from PubMed, Science Direct, and Web of Science, we have gathered substantial evidence showcasing WA’s significant anti-tumor effects against a wide range of cancers in both in vitro and in vivo studies. Mechanistically, WA exerts its anti-tumor influence by inducing cell cycle arrest, apoptosis, autophagy, and ferroptosis. Additionally, it inhibits cell proliferation, cancer stem cells, tumor metastasis, and also suppresses epithelial-mesenchymal transition (EMT) and angiogenesis. Several studies have identified direct target proteins of WA, such as vimentin, Hsp90, annexin II and mFAM72A, while BCR-ABL, Mortalin (mtHsp70), Nrf2, and c-MYB are potential targets of WA. Notwithstanding its remarkable anti-tumor efficacy, there are some limitations associated with WA, including potential toxicity and poor oral bioavailability, which need to be addressed when considering it as an anti-tumor candidate agent. Nevertheless, I given its promising anti-tumor attributes, WA remains an encouraging candidate for future drug development. Unveiling the exact target and comprehensive mechanism of WA’s action represents a crucial research direction to pursue in the future.

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Cytoprotective autophagy induction by withaferin A in prostate cancer cells involves GABARAPL1

Cited by 14 publications

References 30 publications

Forkhead Box Q1 is a novel regulator of autophagy in breast cancer cells

Forkhead Box Q1 is a novel regulator of autophagy in breast cancer cells

Withanolides: Promising candidates for cancer therapy

Withaferin A: A Dietary Supplement with Promising Potential as an Anti-Tumor Therapeutic for Cancer Treatment - Pharmacology and Mechanisms

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