Targeting 3-phosphoinositide-dependent protein kinase 1 associated with drug-resistant renal cell carcinoma using new oridonin analogs

Zhou, Jiancheng; Yun, Eun Joo; Chen, Wei; Ding, Ye; Wu, Kaijie; Wang, Bin; Ding, Chunyong; Hernández, Elizabeth; Santoyo, John; Pong, Rey-Chen; Chen, Haiying; He, Dalin; Zhou, Jia; Hsieh, Jer Tsong

doi:10.1038/cddis.2017.121

Cited by 23 publications

(16 citation statements)

References 34 publications

(40 reference statements)

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“…Oridonin phosphate, another derivative, is reported to induce autophagy, which can enhance apoptosis in human breast cancer MDA-MB-436 cells [583]. A novel analog of oridonin, CYD 6-17, inhibits tumor growth in bladder cancer UMUC3 xenograft mice and renal carcinoma 786-O xenograft mice [584,585]. In addition, drug delivery system is also developed to improve the bioavailability of oridonin.…”

Section: Oridoninmentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Section: Oridoninmentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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“…The hit compound, CYD0618 (Figure 3), induced a threefold shrinkage of the tumor volume in a triple-negative breast cancer MDA-MB-231 xenograft model at a dose of 5 mg/kg, showing much higher efficacy than parent oridonin [19]. Later, Zhou et al reported another oridonin analog, CYD-6-17 ( Figure 3), which significantly inhibited renal cell carcinoma tumor growth in vivo by targeting 3-phosphoinositide-dependent protein kinase 1 (PDPK1) and its downstream pathways [20].…”

Section: Thiazole Derivatives With In Vivo Efficacymentioning

confidence: 99%

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

Ramos-Inza¹,

Aydillo²,

Sanmartín³

et al. 2020

Heterocycles - Synthesis and Biological Activities

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Currently, cancer is one of the major health problems of the human population and prominent cause of death. Thiazole ring has demonstrated many pharmacological activities including anticancer. This scaffold has been found alone or incorporated into the diversity of therapeutic active agents such as tiazofurin, dasatinib, and bleomycin, which are well-known antineoplastic drugs. Recently, most of the compounds isolated from natural sources containing thiazole moiety exhibit notable cytotoxicities and present antitumor potential. In this context, several structural changes have been made in the original structure, such as the incorporation of different substituents or the fusion with other carbo-and heterocycles, in order to increase the antitumoral potency. Related to mechanism of action of these derivatives, some of them act through kinase modulation, polymerization inhibition of microtubule, pro-matrix metalloproteinase activation, signal transducer activation of transcription 3, histone deacetylase inhibition, etc.

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“…is effect suggests its potential application in combination with chemotherapeutic agents for cancer treatment [33,34].…”

Section: Discussionmentioning

confidence: 99%

Oridonin Attenuates Lipopolysaccharide-Induced ROS Accumulation and Inflammation in HK-2 Cells

Huang

Cui

Hsu

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Renal tubulointerstitial inflammation plays an important role in chronic kidney disease (CKD). Inflammation reduction is a good strategy to combat CKD. Oridonin, an ent-kaurane diterpenoid isolated from Rabdosia rubescens (Donglingcao), is considered as an effective natural candidate for the treatment of anti-inflammatory, antiviral, and antibacterial activities, including liver fibrosis and many tumors; however, no study has demonstrated its effect on lipopolysaccharide- (LPS-) induced renal inflammation. To investigate the anti-inflammatory effects of oridonin on human renal proximal tubular epithelial cells (HK-2 cells), the expression levels of c-Jun N-terminal kinase (JNK) and reactive oxygen species (ROS) were evaluated by Western blot analysis and 2′,7′-dichlorofluorescein diacetate (DCF-DA) staining, respectively. The level of intracellular ROS increased in a dose-dependent manner following LPS treatment, whereas oridonin inhibited this effect, suggestive of its ability to prevent ROS accumulation. As the mitogen-activated protein kinase (MAPK) family of enzymes plays an important role in physiological responses, we examined the activation of JNK by Western blotting and found that oridonin attenuated LPS-induced JNK phosphorylation. Oridonin also attenuated RAW 264.7 cell chemotaxis towards LPS-treated HK-2 cells. Taken together, oridonin protected against LPS-induced inflammation including ROS accumulation, JNK activation, NF-κB nuclear translocation in HK-2 cells, and functionally blocked macrophage chemotaxis towards LPS-treated HK-2 cells. Oridonin may exhibit therapeutic potential by the anti-inflammation effect in LPS-treated HK-2 cells.

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Targeting 3-phosphoinositide-dependent protein kinase 1 associated with drug-resistant renal cell carcinoma using new oridonin analogs

Cited by 23 publications

References 34 publications

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Thiazole Moiety: An Interesting Scaffold for Developing New Antitumoral Compounds

Oridonin Attenuates Lipopolysaccharide-Induced ROS Accumulation and Inflammation in HK-2 Cells

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