Application of natural products for inducing ferroptosis in tumor cells

Wu, Zhengxin; Zhong, Min; Liu, Yu; Xiong, Yubo; Gao, Zhi; Ma, Jianchao; Zhuang, Guohong; Hong, Xuehui

doi:10.1002/bab.2096

Cited by 28 publications

(26 citation statements)

References 60 publications

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“…For example, solanine, a glycoside present in potatoes, tomatoes, and eggplant, has been shown to decrease glutathione (GSH) levels by enhancing the ROS production in HepG2 cells [185]. Reduced GSH synthesis can indirectly affect the activity of GPX4, and it is reasonable to hypothesize that solanine-induced cell death at least partially involves ferroptosis [186].…”

Section: Polysaccharides As Ferroptosis Switchersmentioning

confidence: 99%

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

et al. 2021

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Neurodegenerative diseases are a serious and widespread global public health burden amongst aging populations. The total estimated worldwide global cost of dementia was US$818 billion in 2015 and has been projected to rise to 2 trillion US$ by 2030. While advances have been made to understand different neurodegenerative disease mechanisms, effective therapeutic strategies do not generally exist. Several drugs have been proposed in the last two decades for the treatment of different types of neurodegenerative diseases, with little therapeutic benefit, and often with severe adverse and side effects. Thus, the search for novel drugs with higher efficacy and fewer drawbacks is an ongoing challenge in the treatment of neurodegenerative disease. Several natural compounds including polysaccharides have demonstrated neuroprotective and even therapeutic effects. Natural polysaccharides are widely distributed in plants, animals, algae, bacterial and fungal species, and have received considerable attention for their wide-ranging bioactivity, including their antioxidant, anti-neuroinflammatory, anticholinesterase and anti-amyloidogenic effects. In this review, we summarize different mechanisms involved in neurodegenerative diseases and the neuroprotective effects of natural polysaccharides, highlighting their potential role in the prevention and therapy of neurodegenerative disease.

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Section: Polysaccharides As Ferroptosis Switchersmentioning

confidence: 99%

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

et al. 2021

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“…Designing combination therapies based on ferroptosis processes in combination with nanomedicine is also an attractive line of research. Natural products, such as flavonoids, quinones, alkaloids, terpenoids, saponins, polysaccharides, polyphenols, and lignans, can increase intracellular reactive oxygen species and disrupt redox homeostasis (Wu et al, 2022). However, the pharmacological mechanism of these substances in ferroptosis still needs further study.…”

Section: Introductionmentioning

confidence: 99%

Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis

et al. 2023

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Pancreatic cancer is a common gastrointestinal tract malignancy. Currently, the therapeutic strategies for pancreatic cancers include surgery, radiotherapy, and chemotherapy; however, the surgical procedure is invasive, and the overall curative outcomes are poor. Furthermore, pancreatic cancers are usually asymptomatic during early stages and have a high degree of malignancy, along with a high rate of recurrence and metastasis, thereby increasing the risk of mortality. Studies have shown that ferroptosis regulates cell proliferation and tumour growth and reduces drug resistance. Hence, ferroptosis could play a role in preventing and treating cancers. Wogonin is a flavonoid with anticancer activity against various cancers, including pancreatic cancer. It is extracted from the root of Scutellaria baicalensis Georgi. In this study, we show that wogonin inhibits the survival and proliferation of human pancreatic cancer cell lines and induces cell death. We performed RNA-sequencing and analysed the differentially expressed gene and potential molecular mechanism to determine if wogonin reduced cell survival via ferroptosis. Our results showed that wogonin upregulates the levels of Fe2+, lipid peroxidation and superoxide and decreases the protein expression levels of ferroptosis suppressor genes, and downregulates level of glutathione in pancreatic cancer cells. In addition, ferroptosis inhibitors rescue the ferroptosis-related events induced by wogonin, thereby confirming the role of ferroptosis. A significant increase in ferroptosis-related events was observed after treatment with both wogonin and ferroptosis inducer. These results show that wogonin could significantly reduces pancreatic cancer cell proliferation and induce ferroptosis via the Nrf2/GPX4 axis. Therefore, wogonin could be potentially used for treating patients with pancreatic cancer.

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“…Moreover, additional limitations of currently used combinatorial therapeutic modalities include drug toxicity, off-target side effects, and exorbitant costs. To overcome these unmet clinical challenges for patients with CRC, there is an imperative need to identify and evaluate other safe and cost-effective modalities that can be used as potential adjunctive and integrative medicine approaches [ 5 , 6 ].…”

Section: Introductionmentioning

confidence: 99%

“…Several naturally occurring, botanical-driven compounds have recently been scientifically interrogated, offering multi-targeted and safer therapeutic options vis-a-vis conventional cancer chemotherapy [ 5 , 7 , 8 ]. Among these, curcumin, extracted from Curcuma longa, is one of the most studied compounds due to its potent anti-cancer activity in various human cancers [ 6 , 7 , 8 ].…”

Section: Introductionmentioning

confidence: 99%

“…Ferroptosis is a unique type of programmed cell death process that depends on the intracellular accumulation of iron, followed by enhanced production of reactive oxygen species (ROS) and lipid peroxides, eventually promoting iron-dependent cell death in cancer cells [ 5 , 18 , 19 ]. Recently, ferroptosis has been considered an endogenous anticancer mechanism and is actively being studied to develop novel therapeutic targets in cancer [ 5 ]. In this context, curcumin and other naturally-occurring botanicals have also been shown to be ferroptosis inducers in cancer cells [ 5 , 16 , 20 , 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

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Curcumin and Andrographis Exhibit Anti-Tumor Effects in Colorectal Cancer via Activation of Ferroptosis and Dual Suppression of Glutathione Peroxidase-4 and Ferroptosis Suppressor Protein-1

Miyazaki

Shimada

et al. 2023

Pharmaceuticals

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Colorectal cancer (CRC) is the leading cause of cancer-related deaths worldwide. The limitations of current chemotherapeutic drugs in CRC include their toxicity, side effects, and exorbitant costs. To assess these unmet needs in CRC treatment, several naturally occurring compounds, including curcumin and andrographis, have gained increasing attention due to their multi-targeted functionality and safety vs. conventional drugs. In the current study, we revealed that a combination of curcumin and andrographis exhibited superior anti-tumor effects by inhibiting cell proliferation, invasion, colony formation, and inducing apoptosis. Genome-wide transcriptomic expression profiling analysis revealed that curcumin and andrographis activated the ferroptosis pathway. Moreover, we confirmed the gene and protein expression of glutathione peroxidase 4 (GPX-4) and ferroptosis suppressor protein 1 (FSP-1), the two major negative regulators of ferroptosis, were downregulated by this combined treatment. With this regimen, we also observed that intracellular accumulation of reactive oxygen species and lipid peroxides were induced in CRC cells. These cell line findings were validated in patient-derived organoids. In conclusion, our study revealed that combined treatment with curcumin and andrographis exhibited anti-tumorigenic effects in CRC cells through activation of ferroptosis and by dual suppression of GPX-4 and FSP-1, which have significant potential implications for the adjunctive treatment of CRC patients.

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Application of natural products for inducing ferroptosis in tumor cells

Cited by 28 publications

References 60 publications

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

Natural Polysaccharides as Preventive and Therapeutic Horizon for Neurodegenerative Diseases

Wogonin induces ferroptosis in pancreatic cancer cells by inhibiting the Nrf2/GPX4 axis

Curcumin and Andrographis Exhibit Anti-Tumor Effects in Colorectal Cancer via Activation of Ferroptosis and Dual Suppression of Glutathione Peroxidase-4 and Ferroptosis Suppressor Protein-1

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