Molecular targets of gambogic acid in cancer: recent trends and advancements

Mondal, Rajkumar; Tuli, Hardeep Singh; Kumar, Gaurav; Sharma, Anil Kumar

doi:10.1007/s13277-016-5194-8

Cited by 82 publications

(47 citation statements)

References 103 publications

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“…In recent years, the antitumour effects of GA have been identified in various types of cancers, including hepatoma, lung, epithelial cervical, prostate, pancreatic and gastric cancer . Multiple signalling pathways have been described for GA treatment of individual cancer cell lines . Our results and literature have shown inhibitory effect of GA in malignant melanoma .…”

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confidence: 60%

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Liang

Zhang

Qin

et al. 2018

Basic Clin Pharma Tox

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Malignant melanoma is an aggressive form of cancer which is highly resistant to chemotherapy. We have previously found that gambogic acid (GA), a kind of polyprenylated xanthone, exhibits an antitumour role in melanoma. The study was designed to investigate novel mechanisms of the antitumour effect of GA in melanoma cells and implanted nude mice. Gambogic acid significantly decreased cell viability, increased apoptosis and reduced migration and invasion in A375 cells. In addition, cisplatin-induced cytotoxicity in both A375 and A375/CDDP cells was increased by GA. The expression of miR-199a-3p was increased by GA in A375 cells and implanted tumours, and inhibition of miR-199a-3p significantly prevented GA-induced effect on cell viability, apoptosis, migration, invasion and cisplatin sensitivity in A375 cells. miR-199a-3p mimics reduced tumour weight and volume in vivo and decreased cell viability, increased apoptosis and reduced migration and invasion in vitro. miR-199a-3p expression was decreased in melanoma tissues and cells, as compared with their controls. miR-199a-3p possessed a potential binding site in the 3'-UTR of zinc finger E-box binding homeobox (ZEB1). ZEB1 expression was increased in melanoma tissues and cells, as compared with their controls. ZEB1 and miR-199a-3p expression was negatively correlated in melanoma tissues. The expression of ZEB1 was decreased by GA in A375 cells and implanted tumours, and up-regulation of ZEB1 significantly prevented GA-induced effect on cell viability, apoptosis, migration, invasion and cisplatin sensitivity. Down-regulation of ZEB1 reduced tumour weight and volume in vivo and decreased cell viability, increased apoptosis and reduced migration and invasion in vitro. We identified the important roles of miR-199a-3p and ZEB1 in melanoma and elucidated the tumour suppressor function of miR-199a-3p through inhibition of ZEB1. The results highlight the importance of miR-199a-3p-ZEB1 signalling in antitumour effect of GA in malignant melanoma and provide novel targets for the chemotherapy of melanoma.

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supporting

confidence: 60%

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Liang

Zhang

Qin

et al. 2018

Basic Clin Pharma Tox

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“…Cancer cells exhibit high metabolic rate to fulfil their energy requirements that in turn is found to be associated with the neovascularization (angiogenesis). A number of studies have reported the involvement of a variety of transcriptional (ERK 1/2, Akt, and MAPK) and growth factors (VEGF and FGF) in the tumour microenvironment for the neovascularization (Kashyap, Rajkumar Mondal, Tuli, Gaurav Kumar, & Sharma, 2016;Kashyap, Sonam Mittal, Sak, Singhal, & Tuli, 2016;Kumar, Mittal, Sak, & Tuli, 2016;Tuli, Sandhu, Sharma, & Gandhi, 2014). These factors are being targeted as therapeutic approach for the cure of cancer in advanced stages (Fig.…”

Section: Anti-angiogenesis Effect Of Kaempferolmentioning

confidence: 99%

“…However, the scientific community should always endeavour to ameliorate the potency of such wondrous molecules. As the structure of KMF revealed the availability of electron donor atoms, such as oxygen which can make the co-ordinate bond with metal atoms and resulting metal complexes of KMF may further boost its biological activity (Kashyap, Rajkumar Mondal, et al, 2016;Kashyap, Sonam Mittal, et al, 2016;. Computational implements like QSAR models can be acclimated to explore the unknown molecular interactions of KMF with recognized cellular receptors (Bose, Michael, Prashanth, & Chitraa, 2015).…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

Kashyap

Sharma

Tuli

et al. 2017

Journal of Functional Foods

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177

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a b s t r a c tThe consumption of diet-based naturally bioactive metabolites is preferred to synthetic material in order to avert health-associated disorders. Among the plant-derived polyphenols, kaempferol (KMF) is considered as a valuable functional food ingredient with a broad range of therapeutic applications such as anti-cancer, antioxidant and anti-inflammatory uses. KMF acts on a range of intracellular as well as extracellular targets involved in the cell signaling pathways that in turn are known to regulate the hallmarks of cancer growth progressions like apoptosis, cell cycle, invasion or metastasis, angiogenesis and inflammation. Importantly, the understanding of mechanisms of action of KMF-mediated therapeutic effects may help the scientific community to design novel strategies for the treatment of dreadful diseases. The current review summarizes the various types of molecular targets of KMF in cancer cells as well as other health-associated disorders. In addition, this review also highlights the absorption, metabolism and epidemiological findings.

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“…Many in vivo and in vitro studies have demonstrated the potent anticancer activity of gambogic acid, modulating several targets, including induction of apoptosis, cell proliferation arrest and autophagy, and inhibition of telomerase. It also possesses antimetastasis, anti‐angiogenesis and anti‐inflammatory effects …”

Section: Mechanisms Of Actionmentioning

confidence: 99%

“…It also possesses antimetastasis, anti-angiogenesis and anti-inflammatory effects. [221] Several studies have already demonstrated that gambogic acid can be a potent apoptosis inducer, preventing tumor growth. One of its mechanisms of action is related to the increase in p53 expression and the suppression of MDM2 protein.…”

Section: Derivativesmentioning

confidence: 99%

Xanthones and Cancer: from Natural Sources to Mechanisms of Action

Klein‐Júnior

Campos

Niero

et al. 2020

Chemistry & Biodiversity

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Xanthones are a class of heterocyclic natural products that have been widely studied for their pharmacological potential. In fact, they have been serving as scaffolds for the design of derivatives focusing on drug development. One of the main study targets of xanthones is their anticancer activity. Several compounds belonging to this class have already demonstrated cytotoxic and antitumor effects, making it a promising group for further exploration. This review therefore focuses on recently published studies, emphasizing their natural and synthetic sources and describing the main mechanisms of action responsible for the anticancer effect of promising xanthones.

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Molecular targets of gambogic acid in cancer: recent trends and advancements

Cited by 82 publications

References 103 publications

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Gambogic Acid Inhibits Melanoma through Regulation of miR‐199a‐3p/ZEB1 Signalling

Kaempferol – A dietary anticancer molecule with multiple mechanisms of action: Recent trends and advancements

Xanthones and Cancer: from Natural Sources to Mechanisms of Action

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