Cryptotanshinone Inhibites Bladder Cancer Cell Proliferation and Promotes Apoptosis via the PTEN/PI3K/AKT Pathway

Liu, Yadong; Lin, Fanlu; Chen, Yaodong; Wang, Rui; Liu, Jiannan; Jin, Yinshan; An, Ruihua

doi:10.7150/jca.31422

Cited by 38 publications

(28 citation statements)

References 40 publications

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“…Besides, PI3K/Akt axis triggers resistance of cancer cells into chemotherapy, PTEN is able to inhibit PI3K/Akt signaling pathway (Alzahrani, 2019). Notably, accumulating data demonstrates that CT can target PI3K/Akt signaling pathway, its down‐stream (such as GSK‐3β) and upstream (PTEN) mediators (Kim, Kang, & Kwon, 2018; Liu et al, 2020). Inhibition of PI3K/Akt pathway by CT mediates its inhibitory effect on migration and proliferation of cancer cells (Zhang, Wen, et al, 2018).…”

Section: Cryptotanshinone As a Modulator Of Molecular Pathways In Difmentioning

confidence: 99%

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Ashrafizadeh

Zarrabi

Orouei

et al. 2020

Phytotherapy Research

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In respect to the enhanced incidence rate of cancer worldwide, studies have focused on cancer therapy using novel strategies. Chemotherapy is a common strategy in cancer therapy, but its adverse effects and chemoresistance have limited its efficacy. So, attempts have been directed towards minimally invasive cancer therapy using plant derived‐natural compounds. Cryptotanshinone (CT) is a component of salvia miltiorrihiza Bunge, well‐known as Danshen and has a variety of therapeutic and biological activities such as antioxidant, anti‐inflammatory, anti‐diabetic and neuroprotective. Recently, studies have focused on anti‐tumor activity of CT against different cancers. Notably, this herbal compound is efficient in cancer therapy by targeting various molecular signaling pathways. In the present review, we mechanistically describe the anti‐tumor activity of CT with an emphasis on molecular signaling pathways. Then, we evaluate the potential of CT in cancer immunotherapy and enhancing the efficacy of chemotherapy by sensitizing cancer cells into anti‐tumor activity of chemotherapeutic agents, and elevating accumulation of anti‐tumor drugs in cancer cells. Finally, we mention strategies to enhance the anti‐tumor activity of CT, for instance, using nanoparticles to provide targeted drug delivery.

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Section: Cryptotanshinone As a Modulator Of Molecular Pathways In Difmentioning

confidence: 99%

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Ashrafizadeh

Zarrabi

Orouei

et al. 2020

Phytotherapy Research

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“…Therefore, the exploration of new drugs and new methods for the treatment of lung cancer requires an urgent attention. A large number of basic research and clinical practice have shown that natural products can play an important role in the tumour prevention and rehabilitation of cancer patients ( Kim et al, 2020 ; Liu et al, 2020 ; Yeh et al, 2020 ). Their reliable source and high safety are the features, which make them the main source of new drug development.…”

Section: Discussionmentioning

confidence: 99%

In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway

et al. 2021

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Lung cancer is the most leading cause of cancer mortality throughout the world, of which about 85% cases comprise the non-small cell lung cancer (NSCLC). Estrogen and estrogen receptors are known to be involved in the pathogenesis and development of lung cancer. Dioscorea oppositifolia L. is a traditional Chinese medicine and a nutritious food, and can be an excellent candidate as an anti-cancer agent owing to its estrogen-like effects. However, the stems and leaves of D. oppositifolia L. are piled up in the field as a waste, causing environmental pollution and waste of resources. In the present study, a new diphenylethane (D1) was isolated from the stems and leaves of D. oppositifolia L. It was observed that D1 reduced the cell viability, migration, energy metabolism, and induced apoptosis in the A549 cells. Mechanistic studies showed that D1 reduced the STAT3 nuclear localization and downregulated the expression of the STAT3 target genes like Mcl-1, Bcl-xL and MMP-2 that are involved in the cell survival and mobility. Moreover, our results indicated that D1 exhibited estrogenic activities mediated by ERβ, and antagonising ERβ decreased the cytotoxic effect of D1 in A549 cells. In addition, inhibition of the nuclear translocation of STAT3 did not interfere with the binding of D1 and ERβ. However, after antagonizing ERβ, the nuclear translocation of STAT3 increased, thereby demonstrating that STAT3 was the downstream signaling molecule of ERβ. In conclusion, the D1 mediated anti-NSCLC in vitro effects or at least in part can be attributed to the ERβ-STAT3 signaling. Our ﬁndings suggest the role of D1 in treating NSCLC on a molecular level, and can help to improve the comprehensive utilization rate of D. oppositifolia L.

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“…Activated caspase-9 can activate procaspase-3 downstream, which can further cleave PARP, leading to the apoptotic cascade 13,42,47 . Activated caspase-3 also induces the downstream mitochondrial apoptotic pathway, thereby inhibiting AKT 43,[48][49][50][51] . Time-dependent cleavage of caspase-3, caspase-9, and PARP was observed in the DHW-208 treatment cells indicating that DHW-208 can reduce activity of the caspase (intrinsic) pathway.…”

Section: Discussionmentioning

confidence: 99%

A novel 4-aminoquinazoline derivative, DHW-208, suppresses the growth of human breast cancer cells by targeting the PI3K/AKT/mTOR pathway

et al. 2020

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Breast cancer is one of the most frequent cancers among women worldwide. However, there is still no effective therapeutic strategy for advanced breast cancer that has metastasized. Aberrant activation of the PI3K/AKT/mTOR pathway is an essential step for the growth of human breast cancers. In our previous study, we designed and synthesized DHW-208 (2,4-difluoro-N-(5-(4-((1-(2-hydroxyethyl)-1H-pyrazol-4-yl)amino)quinazolin-6-yl)-2methoxypyridin-3-yl)benzenesulfonamide) as a novel pan-PI3K inhibitor. This study aimed to assess the therapeutic efficacy of DHW-208 in breast cancer and investigate its underlying mechanism. We found that DHW-208 inhibited the growth, proliferation, migration, and invasion of breast cancer cells. Moreover, DHW-208 induced breast cancer cell apoptosis via the mitochondrial pathway and induced G0/G1 cell-cycle arrest. In vitro results show that DHW-208 is a dual inhibitor of PI3K and mTOR, and suppress the growth of human breast cancer cells by targeting the PI3K/AKT/ mTOR pathway. Consistent with the in vitro results, in vivo studies demonstrated that DHW-208 elicits an antitumor effect by inhibiting the PI3K/AKT/mTOR-signaling pathway with a high degree of safety in breast cancer. Above all, we report for the first time that DHW-208 suppressed the growth of human breast cancer cells by inhibiting the PI3K/AKT/ mTOR-signaling pathway both in vivo and in vitro. Our study may provide evidence for the use of DHW-208 as an effective, novel therapeutic candidate for the treatment of human breast cancers in clinical trials.

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Cryptotanshinone Inhibites Bladder Cancer Cell Proliferation and Promotes Apoptosis via the PTEN/PI3K/AKT Pathway

Cited by 38 publications

References 40 publications

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

In vitro Non-Small Cell Lung Cancer Inhibitory Effect by New Diphenylethane Isolated From Stems and Leaves of Dioscorea oppositifolia L. via ERβ-STAT3 Pathway

A novel 4-aminoquinazoline derivative, DHW-208, suppresses the growth of human breast cancer cells by targeting the PI3K/AKT/mTOR pathway

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