Sanguinarine Induces H2O2-Dependent Apoptosis and Ferroptosis in Human Cervical Cancer

Alakkal, Ameer; Thayyullathil, Faisal; Pallichankandy, Siraj; Karthikeyan, S.; Cheratta, Anees Rahman; Galadari, Sehamuddin

doi:10.3390/biomedicines10081795

Cited by 15 publications

(18 citation statements)

References 25 publications

(41 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sanguinaria canadensis is the major source of sanguinarine, a quaternary benzophenanthridine alkaloid with anticancer effects (Galadari et al, 2017 ). Very recently, sanguinarine was shown to induce apoptosis and ferroptosis in human cervical cancer (HeLa) cells (Alakkal et al, 2022 ). Both regulated forms of cell death were evoked through sanguinarine-dependent ROS production, especially H 2 O 2 .…”

Section: Natural Compounds As Ferroptosis Inducersmentioning

confidence: 99%

Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills

Consoli

Fallica

Sorrenti

et al. 2024

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: The multifactorial nature of the mechanisms implicated in cancer development still represents a major issue for the success of established antitumor therapies. The discovery of ferroptosis, a novel form of programmed cell death distinct from apoptosis, along with the identification of the molecular pathways activated during its execution, has led to the uncovering of novel molecules characterized by ferroptosis-inducing properties. Recent advances: As of today, the ferroptosis-inducing properties of compounds derived from natural sources have been investigated and interesting findings have been reported both in vitro and in vivo . Critical Issues: Despite the efforts made so far, only a limited number of synthetic compounds have been identified as ferroptosis inducers, and their utilization is still limited to basic research. In this review, we analyzed the most important biochemical pathways involved in ferroptosis execution, with particular attention to the newest literature findings on canonical and non-canonical hallmarks, together with mechanisms of action of natural compounds identified as novel ferroptosis inducers. Compounds have been classified based on their chemical structure, and modulation of ferroptosis-related biochemical pathways has been reported. Future Directions: The outcomes herein collected represent a fascinating starting point from which to take hints for future drug discovery studies aimed at identifying ferroptosis-inducing natural compounds for anticancer therapies. Antioxid. Redox Signal. 40, 40–85.

show abstract

Section: Natural Compounds As Ferroptosis Inducersmentioning

confidence: 99%

Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills

Consoli

Fallica

Sorrenti

et al. 2024

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

show abstract

“…This study suggests that OA may be a potential anticancer drug for cervical cancer. According to research on Sanguinarine (SNG) by Alakkal et al [56], SNG caused ferroptosis through SL7A11 and apoptosis through caspase-3 in human cervical carcinoma. A second death mechanism was likewise blocked by the administration of an RCD inhibitor [56].…”

Section: Ferroptosis and Cervical Cancermentioning

confidence: 99%

“…According to research on Sanguinarine (SNG) by Alakkal et al [56], SNG caused ferroptosis through SL7A11 and apoptosis through caspase-3 in human cervical carcinoma. A second death mechanism was likewise blocked by the administration of an RCD inhibitor [56]. This raises the question of whether cancer cells' regulation of H 2 O 2 is what leads to medication resistance.…”

Section: Ferroptosis and Cervical Cancermentioning

confidence: 99%

Ferroptosis’s Role in Genitourinary System Cancer

Liu¹,

Yang²,

Wang³

et al. 2022

Oncologie

View full text Add to dashboard Cite

A cell is the basic unit of life, and death is inevitable for any cell. However, cancer cells that deviate from the normal track can resist death and survive. Ferroptosis is recently discovered as a modulated cell death different from other known forms of cell death in morphology, biochemistry, and genetics. It is characterized by irondependent lipid peroxidation regulated by various metabolic pathways. The incidence and mortality of genitourinary system cancer have been increasing recently. Although clinical practice therapy techniques have improved, no plan with a positive prognosis has been identified. For the therapy of cancer, ferroptosis opens up new avenues. Many studies have shown a complex link between ferroptosis and cancer, while some studies have also found the role of ferroptosis in genitourinary system-related cancers and therapeutic prospects. This article reviews the ferroptosis research progress in genitourinary system cancers, including bladder cancer, prostate cancer, ovarian cancer, and cervical cancer. It will also provide new ideas for the treatment of these cancers.

show abstract

“…Sanguinarine chloride (S.C) is a natural benzophenanthridine alkaloid extracted from various sources, including the roots of Sanguinaria canadensis, seeds of Argemone Mexicana, and the leaves and fruits of Macleaya cordata [ 13 ]. Numerous studies have reported its pharmacological activity in cancer therapy [ 13 – 15 ].…”

Section: Introductionmentioning

confidence: 99%

Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer

Liu,

Tao,

et al. 2024

Chin Med

View full text Add to dashboard Cite

Background Sanguinarine chloride (S.C) is a benzophenanthrine alkaloid derived from the root of sanguinaria canadensis and other poppy-fumaria species. Studies have reported that S.C exhibits antioxidant, anti-inflammatory, proapoptotic, and growth inhibitory effects, which contribute to its anti-cancer properties. Recent studies suggested that the antitumor effect of S.C through inducing ferroptosis in some cancers. Nevertheless, the precise mechanism underlying the regulation of ferroptosis by S.C remains poorly understood. Methods A small molecule library was constructed based on FDA and CFDA approved small molecular drugs. CCK-8 assay was applied to evaluate the effects of the small molecule compound on tumor cell viability. Prostate cancer cells were treated with S.C and then the cell viability and migration ability were assessed using CCK8, colony formation and wound healing assay. Reactive oxygen species (ROS) and iron accumulation were quantified through flow cytometry analysis. The levels of malondialdehyde (MDA) and total glutathione (GSH) were measured using commercially available kits. RNA-seq analysis was performed to identify differentially expressed genes (DEGs) among the treatment groups. Western blotting and qPCR were utilized to investigate the expression of relevant proteins and genes. In vivo experiments employed a xenograft mice model to evaluate the anti-cancer efficacy of S.C. Results Our study demonstrated that S.C effectively inhibited the viability of various prostate cancer cells. Notably, S.C exhibited the ability to enhance the cytotoxicity of docetaxel in DU145 cells. We found that S.C-induced cell death partially relied on the induction of ferroptosis, which was mediated through up-regulation of HMOX1 protein. Additionally, our investigation revealed that S.C treatment decreased the stability of BACH1 protein, which contributed to HMOX1expression. We further identified that S.C-induced ROS caused BACH1 instability by suppressing USP47expression. Moreover, In DU145 xenograft model, we found S.C significantly inhibited prostate cancer growth, highlighting its potential as a therapeutic strategy. Collectively, these findings provide evidence that S.C could induce regulated cell death (RCD) in prostate cancer cells and effectively inhibit tumor growth via triggering ferroptosis. This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting ROS/USP47/BACH1/HMOX1 axis. Conclusion This study provides evidence that S.C effectively suppresses tumor progression and induces ferroptosis in prostate cancer cells by targeting the ROS/USP47/BACH1/HMOX1 axis. These findings offer novel insights into the underlying mechanism by which S.C inhibits the progression of prostate cancer. Furthermore, leveraging the potential of S.C in targeting ferroptosis may present a new therapeutic opportunity for prostate cancer. This study found that S.C induces ferroptosis by targeting the ROS/USP47/BACH1/HMOX1 axis in prostate cancer cells. Graphical Abstract

show abstract

Sanguinarine Induces H2O2-Dependent Apoptosis and Ferroptosis in Human Cervical Cancer

Cited by 15 publications

References 25 publications

Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills

Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills

Ferroptosis’s Role in Genitourinary System Cancer

Sanguinarine chloride induces ferroptosis by regulating ROS/BACH1/HMOX1 signaling pathway in prostate cancer

Contact Info

Product

Resources

About