Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/β-catenin and MAPKs signaling pathways

Yang, Chunmei; Zhang, Lulu; Huang, Huakun; Yuan, Xiaohui; Zhang, Ping; Ye, Caihong; Wei, Mengqi; Huang, Yanran; Luο, Xingguang; Luo, Jinyong

doi:10.1016/j.gendis.2020.07.014

Cited by 17 publications

(6 citation statements)

References 56 publications

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“…MAPK signalling is a double-edged pathway that can promote tumour progression and tumour cell death in vivo and in vitro [40][41][42][43]. The same phenomenon is also observed in osteosarcoma [44][45][46][47][48][49]. Nevertheless, some chemopreventive agents activate MAPK signalling, leading to significant antiosteosarcoma effects [50,51].…”

Section: Discussionmentioning

confidence: 84%

Theaflavin-3,3 $'$ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

Lin

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Globally, osteosarcoma (OS) is the most prevalent form of primary bone cancer in children and adolescents. Traditional neoadjuvant chemotherapy regimens have reached a bottleneck; thus, OS survivors have unsatisfactory outcomes. Theaflavin-3,3 ′ -digallate (TF3) exhibits potent anticancer properties against many human cancers. Nevertheless, the biological effects and the underlying molecular mechanism of TF3 in human OS remain unclear. The objective of this study was to investigate the effects of TF3 on human OS cell lines and mouse xenograft models. The results showed that TF3 reduced cell viability, suppressed cell proliferation, and caused G0/G1 cell cycle arrest in both MG63 and HOS cell lines in a concentration-dependent manner. TF3 also altered the homeostatic mechanisms for iron storage in the examined cell lines, resulting in an excess of labile iron. Unsurprisingly, TF3 caused oxidative stress through reduced glutathione (GSH) exhaustion, reactive oxygen species (ROS) accumulation, and the Fenton reaction, which triggered ferroptosis and apoptosis in the cells. TF3 also induced MAPK signalling pathways, including the ERK, JNK, and p38 MAPK pathways. Furthermore, oxidative stress was shown to be the primary reason for TF3-induced proliferation inhibition, programmed cell death, and MAPK pathway activation in vitro. Moreover, TF3 exhibited markedly strong antitumour efficacy in vivo in mouse models. In summary, this study demonstrates that TF3 concomitantly plays dual roles in apoptotic and ferroptotic cell death by triggering the ROS and MAPK signalling pathways in both in vitro and in vivo models.

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Section: Discussionmentioning

confidence: 84%

Theaflavin-3,3 $'$ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

Lin

Yang

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…Furthermore, it induced the activation of caspase 3 and PARP. Moreover, it decreased tumor growth and metastasis of 143B cells in a xenograft model of osteosarcoma ( Yang C. et al, 2022 ). Alipour et al (2022) examined the effect of cisplatin, alantolactone, and ZnO nanoparticles (ZnONPs) on the induction of apoptosis in the SKOV3 ovarian cancer cell line.…”

Section: Sesquiterpene Lactones With Pro-apoptotic Activities In Cancermentioning

confidence: 99%

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis

Hsu,

Rajabi,

Hamzeloo-Moghadam

et al. 2024

Front. Pharmacol.

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Apoptosis is a programmed cell death comprising two signaling cascades including the intrinsic and extrinsic pathways. This process has been shown to be involved in the therapy response of different cancer types, making it an effective target for treating cancer. Cancer has been considered a challenging issue in global health. Cancer cells possess six biological characteristics during their developmental process known as cancer hallmarks. Hallmarks of cancer include continuous growth signals, unlimited proliferation, resistance to proliferation inhibitors, apoptosis escaping, active angiogenesis, and metastasis. Sesquiterpene lactones are one of the large and diverse groups of planet-derived phytochemicals that can be used as sources for a variety of drugs. Some sesquiterpene lactones possess many biological activities such as anti-inflammatory, anti-viral, anti-microbial, anti-malarial, anticancer, anti-diabetic, and analgesic. This review article briefly overviews the intrinsic and extrinsic pathways of apoptosis and the interactions between the modulators of both pathways. Also, the present review summarizes the potential effects of sesquiterpene lactones on different modulators of the intrinsic and extrinsic pathways of apoptosis in a variety of cancer cell lines and animal models. The main purpose of the present review is to give a clear picture of the current knowledge about the pro-apoptotic effects of sesquiterpene lactones on various cancers to provide future direction in cancer therapeutics.

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“…Ganoderma lucidum, 274 melittin, 275 and dihydrotanshinone I 276 inhibit the Wnt coreceptor LRP5/6 and the Wnt‐associated target genes MMP‐2, MMP‐9, C‐Myc, β‐catenin, and cyclin D1 to block Wnt/β‐catenin signaling and inhibit the EMT process in OS cells, consequently suppressing OS cell proliferation and metastasis. Convallatoxin 277 and alantolactone 278 can inhibit the malignant OS progression by blocking the Wnt/β‐catenin pathway.…”

Section: Mechanism Of Targeting Signaling Pathwaysmentioning

confidence: 99%

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Shen

Lan

et al. 2023

MedComm

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Osteosarcoma (OS) is a highly prevalent bone malignancy among adolescents, accounting for 40% of all primary malignant bone tumors. Neoadjuvant chemotherapy combined with limb‐preserving surgery has effectively reduced patient disability and mortality, but pulmonary metastases and OS cells' resistance to chemotherapeutic agents are pressing challenges in the clinical management of OS. There has been an urgent need to identify new biomarkers for OS to develop specific targeted therapies. Recently, the continued advancements in genomic analysis have contributed to the identification of clinically significant molecular biomarkers for diagnosing OS, acting as therapeutic targets, and predicting prognosis. Additionally, the contemporary molecular classifications have revealed that the signaling pathways, including Wnt/β‐catenin, PI3K/AKT/mTOR, JAK/STAT3, Hippo, Notch, PD‐1/PD‐L1, MAPK, and NF‐κB, have an integral role in OS onset, progression, metastasis, and treatment response. These molecular classifications and biological markers have created new avenues for more accurate OS diagnosis and relevant treatment. We herein present a review of the recent findings for the modulatory role of signaling pathways as possible biological markers and treatment targets for OS. This review also discusses current OS therapeutic approaches, including signaling pathway‐based therapies developed over the past decade. Additionally, the review covers the signaling targets involved in the curative effects of traditional Chinese medicines in the context of expression regulation of relevant genes and proteins through the signaling pathways to inhibit OS cell growth. These findings are expected to provide directions for integrating genomic, molecular, and clinical profiles to enhance OS diagnosis and treatment.

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Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/β-catenin and MAPKs signaling pathways

Cited by 17 publications

References 56 publications

Theaflavin-3,3 $'$ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

Theaflavin-3,3 $'$ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

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Alantolactone inhibits proliferation, metastasis and promotes apoptosis of human osteosarcoma cells by suppressing Wnt/β-catenin and MAPKs signaling pathways

Cited by 17 publications

References 56 publications

Theaflavin-3,3 ′ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

Theaflavin-3,3 ′ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis

Targeting signaling pathways in osteosarcoma: Mechanisms and clinical studies

Contact Info

Product

Resources

About

Theaflavin-3,3 $'$ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts

Theaflavin-3,3 $'$ -Digallate Plays a ROS-Mediated Dual Role in Ferroptosis and Apoptosis via the MAPK Pathway in Human Osteosarcoma Cell Lines and Xenografts