Mangrove dolabrane‐type of diterpenes tagalsins suppresses tumor growth <i>via</i><scp>ROS</scp>‐mediated apoptosis and <scp>ATM/ATR–C</scp>hk1/Chk2‐regulated cell cycle arrest

Neumann, Jennifer; Yang, Yi; Köhler, Rebecca; Giaisi, Marco; Witzens‐Harig, Mathias; Liu, Dong; Krammer, Peter H.; Lin, Wenhan; Li‐Weber, Min

doi:10.1002/ijc.29629

Cited by 26 publications

(15 citation statements)

References 36 publications

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“…to serve a significant role in mediating apoptosis and cell cycle arrest (35,36), and also to promote the sustained activation of JNK (37), thus, the ROS levels were detected. ROS production was significantly increased by andrographolide treatment and the increased ROS production was completely blocked by NAC, an ROS scavenger (Fig.…”

Section: Andrographolide Promotes Ros Generation Which Results In Jnmentioning

confidence: 99%

Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway

Wang

Chen

et al. 2020

Int J Oncol

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Osteosarcoma is the most common primary malignant tumor of the bone and the long-term survival of patients with this disease has remained unsatisfactory over the past several decades. Andrographolide, a traditional drug used in Chinese medicine, has been found to exert a significant antitumor effect against several types of cancer. However, relatively little is known about the effect of andrographolide on osteosarcoma and the underlying mechanisms. In the present study, it was shown that andrographolide inhibited osteosarcoma cell proliferation by arresting the cell cycle at the G2/M phase and increasing caspase-mediated apoptosis. Furthermore, treatment with andrographolide induced JNK activation and increased production of reactive oxygen species (ROS). The andrographolide-triggered apoptosis in osteosarcoma cells was partly abrogated by a JNK inhibitor and completely reversed by a ROS scavenger. Additionally, JNK activation and cell cycle arrest at the G2/M phase were prevented by administration of an ROS scavenger. In vivo, it was also found that andrographolide inhibited tumor growth by increasing the levels of ROS and activating JNK; thus inducing cytotoxicity in primary osteosarcoma cells. Together, the results of the present study suggest that andrographolide caused G2/M arrest and induced cell apoptosis via regulation of the ROS/JNK signaling pathway in osteosarcoma cells. Thus, andrographolide may serve as a promising antitumor therapeutic agent against osteosarcoma.

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Section: Andrographolide Promotes Ros Generation Which Results In Jnmentioning

confidence: 99%

Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway

Wang

Chen

et al. 2020

Int J Oncol

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“…human T-cell leukemia xenogras, via a mechanism involving ROS-mediated apoptosis and cell cycle arrest. 1016 In addition the phenethyl cinnamide micrometam C (Micromelum falcatum) 1017 protects against LPS-induced reactive oxygen species in both zebrash and macrophages, 1018 and limonoids xyloccensin E 1019 and I 1020 (Xylocarpus moluccensis and X. granatum) exhibited antiulcer gastroprotective activities in rats, likely due to an ability to inhibit H + K + -ATPase activity. 1021 14 Miscellaneous…”

Section: Mangrovesmentioning

confidence: 99%

Marine natural products

et al. 2017

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Covering: 2015. Previous review: Nat. Prod. Rep., 2016, 33, 382-431This review covers the literature published in 2015 for marine natural products (MNPs), with 1220 citations (792 for the period January to December 2015) referring to compounds isolated from marine microorganisms and phytoplankton, green, brown and red algae, sponges, cnidarians, bryozoans, molluscs, tunicates, echinoderms, mangroves and other intertidal plants and microorganisms. The emphasis is on new compounds (1340 in 429 papers for 2015), together with the relevant biological activities, source organisms and country of origin. Reviews, biosynthetic studies, first syntheses, and syntheses that lead to the revision of structures or stereochemistries, have been included.

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“…Therefore, it is critical to elucidate the mechanism of DDR in order to treat human diseases, such as cancer. The major regulators of DDR are phosphoinositide 3-kinase (PI3K)-related protein kinases (PIKKs), which include ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and RAD3-related (ATR) (3,6,7). ATM and ATR respond to different types of DNA damage; ATM mainly responds to double-strand breaks (DSBs) while ATR mainly responds to replication stress and UV-induced pyrimidine dimers.…”

Section: Introductionmentioning

confidence: 99%

PTEN enhances G2/M arrest in etoposide-treated MCF-7 cells through activation of the ATM pathway

et al. 2016

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As an effective tumor suppressor, phosphatase and tensin homolog (PTEN) has attracted the increased attention of scientists. Recent studies have shown that PTEN plays unique roles in the DNA damage response (DDR) and can interact with the Chk1 pathway. However, little is known about how PTEN contributes to DDR through the ATM-Chk2 pathway. It is well-known that etoposide induces G2/M arrest in a variety of cell lines, including MCF-7 cells. The DNA damage-induced G2/M arrest results from the activation of protein kinase ataxia telangiectasia mutated (ATM), followed by the activation of Chk2 that subsequently inactivates CDC25C, resulting in G2/M arrest. In the present study, we assessed the contribution of PTEN to the etoposide-induced G2/M cell cycle arrest. PTEN was knocked down in MCF-7 cells by specific shRNA, and the effects of PTEN on the ATM-Chk2 pathway were investigated through various approaches. The results showed that knockdown of PTEN strongly antagonized ATM activation in response to etoposide treatment, and thereby reduced the phosphorylation level of ATM substrates, including H2AX, P53 and Chk2. Furthermore, depletion of PTEN reduced the etoposide-induced phosphorylation of CDC25C and strikingly compromised etoposide-induced G2/M arrest in the MCF-7 cells. Altogether, we demonstrated that PTEN plays a unique role in etoposide-induced G2/M arrest by facilitating the activation of the ATM pathway, and PTEN was required for the proper activation of checkpoints in response to DNA damage in MCF-7 cells.

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Mangrove dolabrane‐type of diterpenes tagalsins suppresses tumor growth viaROS‐mediated apoptosis and ATM/ATR–Chk1/Chk2‐regulated cell cycle arrest

Cited by 26 publications

References 36 publications

Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway

Andrographolide induces apoptosis in human osteosarcoma cells via the ROS/JNK pathway

Marine natural products

PTEN enhances G2/M arrest in etoposide-treated MCF-7 cells through activation of the ATM pathway

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