Cryptotanshinone induces ROS-mediated apoptosis in human gastric cancer cells

Liu, Chang; Sun, Haiyan; Luo, Yunping; Piao, Xiang‐Lan; Wu, Dandan; Li, Meng; Wang, Yue; Zhang, Yi; Wang, Jia-Ru; Wang, Hao; Xu, Wanting; Li, Jin-Qian; Yang, Liu; Wu, Yiqin; Han, Ying‐Hao; Shen, Gui‐Nan; Jin, Meihua; Zang, Yanqing; Li, Jingchun; Nan-zhu, Fang; Cui, Yudong; Jin, Cheng‐Hao

doi:10.18632/oncotarget.23267

Cited by 33 publications

(31 citation statements)

References 46 publications

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“…However, other previous studies confirmed NAC inhibited anti-tumor effect of some chemical agents isolated from the plant, such as britannin, (33) Umbilicaria esculenta, (34) and cryptotanshinone. (35) Consistent with those previous studies, NAC also abolished quercetin-induced NUPR1-depended autophagic cell death in OS cells both in vitro and in vivo. These results also suggested that clinical trials will need to be performed to test if NAC combined with other antioxidants or metabolic modulators are effective in OS.…”

Section: Discussionsupporting

confidence: 92%

Quercetin induced NUPR1-dependent autophagic cell death by disturbing reactive oxygen species homeostasis in osteosarcoma cells

Zeng

Ouyang

et al. 2020

J. Clin. Biochem. Nutr.

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Osteosarcoma is a primary bone aggressive cancer, affecting adolescents worldwide. Quercetin (a natural polyphenolic com pound) is a polyphenolic flavonoid compound found in a variety of plants. It has been demonstrated to exert cytostatic activity against a variety of human cancer, including the human osteo sarcoma. However, its efficacy in the treatment of osteosarcoma and the underlying antitumor mechanism has not been fully elucidated yet. In this study, we exposed MG 63 cells to different concentrations of quercetin (50, 100 and 200 µM) for 24 h. Here, we show that quercetin increased autophagic flux in the MG 63 cells, as evidenced by the upregulation of LC3B II/LC3B I and downregulation of P62/SQSTM1. Moreover, the autophagy inhibitor Bafilomycin A1 or genetic blocking autophagy with ATG5 knock down decreased quercetin induced cell death, indicating quercetin triggered autophagic cell death in MG 63 cells. Specifically, quercetin increased NUPR1 expression and activated of NUPR1 reporter activity, which contributed to the expression of autophagy related genes and subsequent initiated autophagic cell death in osteo sarcoma cells. Importantly, the increased expression NUPR1 were tightly related to the disturbance of reactive oxygen species (ROS) homeostasis, which could be prevented by inhibiting intracellular ROS with NAC. Finally, NAC also abolished quercetin induced autophagic cell death in vivo. Taken together, these data demon strate that quercetin induces osteosarcoma cell death via inducing excessive autophagy, which is mediated through the ROS NUPR1 pathway. Quercetin application may be a promising and practical strategy for osteosarcoma treatment in clinical practice.

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Section: Discussionsupporting

confidence: 92%

Quercetin induced NUPR1-dependent autophagic cell death by disturbing reactive oxygen species homeostasis in osteosarcoma cells

Zeng

Ouyang

et al. 2020

J. Clin. Biochem. Nutr.

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“…CT is one of the tanshinones isolated from Salvia miltiorrhiza Bunge, and now is widely used in several diseases, including high blood pressure, fibrosis, and several malignant tumors. CT was found to induce apoptosis and cell cycle arrest in gastric cancer (GC) cells via reactive oxygen species (ROS)‐mediated MAPK and AKT signaling pathways, and this CT may be a useful compound for the developing anticancer agents for GC . CT also suppressed the proliferation of prostate cancer cells via the inhibition of JNK/STAT3 signaling pathway .…”

Section: Discussionmentioning

confidence: 99%

“…CT has been demonstrated to have anti‐tumor activities in various malignancies, including breast cancer,liver cancer,prostate cancer, and ovarian cancer . CT was found to induced apoptosis and cell cycle arrest in gastric cancer cells via reactive oxygen species (ROS)‐mediated MAPK and AKT signaling pathways . It has been reported that CT was a potent STAT3 inhibitor and inhibited STAT3 Tyr705 phosphorylation effectively in DU145 prostate cancer cells .…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12][13] CT was found to induced apoptosis and cell cycle arrest in gastric cancer cells via reactive oxygen species (ROS)-mediated MAPK and AKT signaling pathways. 14,15 It has been reported that CT was a potent STAT3 inhibitor and inhibited STAT3 Tyr705 phosphorylation effectively in DU145 prostate cancer cells. 16 Therefore, growing evidence indicates that cryptotanshinone is a potent anticancer agent targeting STAT3 protein.…”

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confidence: 99%

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Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

et al. 2018

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Ovarian cancer is the most malignant gynecologic cancer among women worldwide. Cryptotanshinone (CT), isolated from Salvia miltiorrhiza Bunge, has been identified as a potential therapeutic agent in treating several malignant tumors, but the molecular mechanism of CT in ovarian cancer still remains illustrated. Here, we sought to elucidate the regulatory function of CT on cell glucose metabolism in ovarian cancer. The treatment of CT on ovarian cancer cells effectively inhibited glucose uptake and lactate production in ovarian cancer cells. The expression levels of glycolysis‐related proteins, such as GLUT1, LDHA, and HK2, were decreased by the treatment of CT detected by qRT‐PCR and immunoblotting. Mechanistically, CT exerted its anti‐tumor effect by targeting STAT3/SIRT3/HIF‐1α signaling pathway in vitro and in vivo, which could be rescued by the introduction of SIRT3 shRNA in ovarian cancer cells. The clinical data showed that the expression level of STAT3 in ovarian cancer patients’ sera and tissues was positively correlated with those of GLUT1, LDHA, HK2 and HIF‐1α, but negatively with that of SIRT3These findings provide evidence that CT inhibited cellular glycolysis‐induced cell growth and proliferation through repression of STAT3/SIRT3/HIF‐1α signaling pathway, indicating that CT may be developed as a chemotherapeutic agent to treat ovarian cancer.

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“…Because of the NAC that have well‐described antioxidant and radical scavenging activity, it has also been used as an antioxidant in several in many studies (Dodd, Dean, Copolov, Malhi, & Berk, ). Such as, NAC could inhibit the quinalizarin‐induced ROS generation in lung cancer A549 cells and blocked cryptotanshinone‐induced apoptosis in gastric cancer cells (Liu et al, ; Meng et al, ). In this study, to determine the relationship of NTDMNQ‐induced apoptosis and ROS, the NAC was used to pretreat the AGS cells.…”

Section: Discussionmentioning

confidence: 99%

The compound 2‐(naphthalene‐2‐thio)‐5,8‐dimethoxy‐1,4‐naphthoquinone induces apoptosis via reactive oxygen species‐regulated mitogen‐activated protein kinase, protein kinase B, and signal transducer and activator of transcription 3 signaling in human gastric cancer cells

Wang

Shen

Luo

et al. 2018

Drug Development Research

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Hit, Lead & Candidate Discovery It is reported that 1,4-naphthoquinones and their derivatives have potent antitumor activity in various cancers, although their clinical application is limited by observed side effects. To improve the therapeutic efficacy of naphthoquinones in the treatment of cancer and to reduce side effects, we synthesized a novel naphthoquinone derivative, 2-(naphthalene-2-thio)-5,8-dimethoxy-1,4-naphthoquinone (NTDMNQ). In this study, we explored the effects of NTDMNQ on apoptosis in gastric cancer cells with a focus on reactive oxygen species (ROS) production. Our results demonstrated that NTDMNQ exhibited the cytotoxic effects on gastric cancer cells in a dose-dependent manner. NTDMNQ significantly induced mitochondrial-related apoptosis in AGS cells and increased the accumulation of ROS. However, pre-treatment with N-acetyl-L-cysteine (NAC), an ROS scavenger, inhibited the NTDMNQ-induced apoptosis. In addition, NTDMNQ increased the phosphorylation of p38 kinase and c-Jun N-terminal kinase (JNK) and decreased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt), and Signal Transducer and Activator of Transcription 3 (STAT3); these effects were blocked by mitogen-activated protein kinase (MAPK) inhibitor and NAC. Taken together, the present findings indicate that NTDMNQ-induced gastric cancer cell apoptosis via ROS-mediated regulation of the MAPK, Akt, and STAT3 signaling pathways. Therefore, NTDMNQ may be a potential treatment for gastric cancer as well as other tumor types.

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Cryptotanshinone induces ROS-mediated apoptosis in human gastric cancer cells

Cited by 33 publications

References 46 publications

Quercetin induced NUPR1-dependent autophagic cell death by disturbing reactive oxygen species homeostasis in osteosarcoma cells

Quercetin induced NUPR1-dependent autophagic cell death by disturbing reactive oxygen species homeostasis in osteosarcoma cells

Cryptotanshinone suppresses cell proliferation and glucose metabolism via STAT3/SIRT3 signaling pathway in ovarian cancer cells

The compound 2‐(naphthalene‐2‐thio)‐5,8‐dimethoxy‐1,4‐naphthoquinone induces apoptosis via reactive oxygen species‐regulated mitogen‐activated protein kinase, protein kinase B, and signal transducer and activator of transcription 3 signaling in human gastric cancer cells

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