Chrysanthemulide A induces apoptosis through DR5 upregulation via JNK‐mediated autophagosome accumulation in human osteosarcoma cells

Zhuo, Fang-fang; Zhang, Chao; Zhang, Hao; Xia, Yuan‐Zheng; Xue, Gui‐Min; Yang, Lei; Kong, Ling–Yi

doi:10.1002/jcp.27991

Cited by 16 publications

(7 citation statements)

References 57 publications

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“…), but their anti-inflammatory, anticancer and other properties are remarkable. For example, chrysanthemulide A (sesquiterpenoid) of C. indicum induced apoptosis of osteosarcoma by upregulating death receptor 5 via JNK-mediated autophagosome accumulation ( Zhuo et al, 2019 ); it also showed the anti-inflammatory activity via suppressing the LPS-induced NF-κB pathway and down-regulating MAPK activation ( Xue et al, 2018 ); cumambrin A (sesquiterpenoid) suppressed the osteoclast formation, bone resorption, and RANKL-induced signaling pathways in the treatment of osteoporosis ( Zhou et al, 2019a ). The recently discovered sesquiterpenes are subject to the in vitro activity screening ( Jiang et al, 2021a ), whose efficacies and corresponding mechanisms of action warrant further explorations.…”

Section: Pharmacological Propertiesmentioning

confidence: 99%

The genus Chrysanthemum: Phylogeny, biodiversity, phytometabolites, and chemodiversity

et al. 2022

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The ecologically and economically important genus Chrysanthemum contains around 40 species and many hybrids and cultivars. The dried capitulum of Chrysanthemum morifolium (CM) Ramat. Tzvel, i.e., Flos Chrysanthemi, is frequently used in traditional Chinese medicine (TCM) and folk medicine for at least 2,200 years. It has also been a popular tea beverage for about 2,000 years since Han Dynasty in China. However, the origin of different cultivars of CM and the phylogenetic relationship between Chrysanthemum and related Asteraceae genera are still elusive, and there is a lack of comprehensive review about the association between biodiversity and chemodiversity of Chrysanthemum. This article aims to provide a synthetic summary of the phylogeny, biodiversity, phytometabolites and chemodiversity of Chrysanthemum and related taxonomic groups, focusing on CM and its wild relatives. Based on extensive literature review and in light of the medicinal value of chrysanthemum, we give some suggestions for its relationship with some genera/species and future applications. Mining chemodiversity from biodiversity of Chrysanthemum containing subtribe Artemisiinae, as well as mining therapeutic efficacy and other utilities from chemodiversity/biodiversity, is closely related with sustainable conservation and utilization of Artemisiinae resources. There were eight main cultivars of Flos Chrysanthemi, i.e., Hangju, Boju, Gongju, Chuju, Huaiju, Jiju, Chuanju and Qiju, which differ in geographical origins and processing methods. Different CM cultivars originated from various hybridizations between multiple wild species. They mainly contained volatile oils, triterpenes, flavonoids, phenolic acids, polysaccharides, amino acids and other phytometabolites, which have the activities of antimicrobial, anti-viral, antioxidant, anti-aging, anticancer, anti-inflammatory, and closely related taxonomic groups could also be useful as food, medicine and tea. Despite some progresses, the genetic/chemical relationships among varieties, species and relevant genera have yet to be clarified; therefore, the roles of pharmacophylogeny and omics technology are highlighted.

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Section: Pharmacological Propertiesmentioning

confidence: 99%

The genus Chrysanthemum: Phylogeny, biodiversity, phytometabolites, and chemodiversity

et al. 2022

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“…Recent studies have shown that the combination of TRAIL and chemotherapeutic drugs leads to an improvement in the sensitivity of tumor cells to TRAIL. TRAIL is a member of the tumor necrosis factor superfamily, which is able to induce tumor cell apoptosis through binding to DRs on cell membranes with low toxicity to normal tissues and cells (31)(32)(33). TRAIL has an intracellular death domain, which is able to effectively transmit apoptotic signals and induce apoptosis.…”

Section: Discussionmentioning

confidence: 99%

ASPP2 promotes cell apoptosis in cervical cancer through inhibiting autophagy

Jiang

Bian

2022

Exp Ther Med

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Cervical cancer is a common tumor of the reproductive system; however, to the best of the authors' knowledge, the regulation and underlying mechanism of p53 apoptosis-stimulating protein 2 (ASPP2) in cervical cancer has yet to be elucidated. Therefore, the present study aimed to explore the role of ASPP2 in cervical cancer. Tumor tissues were collected for the detection of ASPP2 expression. Experiments wherein ASPP2 was overexpressed were designed to upregulate the expression of ASPP2. The levels of autophagy were subsequently assessed by examining LC3B level via immunofluorescence. Cell Counting Kit-8 assay was then performed to estimate the level of cell proliferation. The cell proliferation level was also measured by EdU staining, and TUNEL assay was used to detect the level of apoptosis. The expression levels of ASPP2, Beclin1 and associated proteins were detected using reverse transcription-quantitative PCR and western blotting analyses. ASPP2 was observed to be markedly reduced in patients with cervical cancer and in cervical cancer cell lines. Overexpression of ASPP2 was found to suppress the expression of Beclin1, and autophagy was also inhibited in cervical cancer cells. Overexpression of ASPP2 also inhibited cell proliferation and promoted apoptosis of cervical cancer cells via the inhibition of autophagy. Additionally, overexpression of ASPP2 was shown to enhance the TNF-related apoptosis-inducing ligand-induced apoptosis of cervical cancer cells via inhibiting autophagy. Taken together, the results of the present study have shown that ASPP2 exerted antitumor effect in cervical cancer by inhibiting cell proliferation and promoting apoptosis partly through inhibiting autophagy. These findings may be useful for the provision of potential targets for cervical cancer therapy.

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“…The c-Jun N-terminal kinase (JNK) signaling pathway was activated by CA, and treatment with JNK siRNAs or inhibitor SP600125 significantly reduced CA-mediated autophagosome accumulation and DR5-mediated cell apoptosis. CA can induce apoptosis according to upregulated DR5 via JNK-mediated autophagosome accumulation and the combined treatment of CA and TRAIL might be a promising therapy for osteosarcoma [61].…”

Section: Antitumor Activitymentioning

confidence: 99%

“…Chrysanthemulide H (86), 8tigloyldesacetylezomontanin (87), chrysanthemulide F (89), chrysanthemulide G (90), chrysanthemulide A (92), chrysanthemulide B (93), chrysanthemulide C (94), chrysanthemulide D (95), and chrysanthemulide E (96) and 98-103 displayed NO production inhibitory activities with IC 50 values ranging from 1.4 to 9.7 µM. The IC 50 value of the positive control drug L-NMMA was 25.8 µM [39,61]. These sesquiterpenoids have great antiinflammatory potential.…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

“…These sesquiterpenoids have great antiinflammatory potential. A mechanistic study revealed that the potential anti-inflammatory activity of compound chrysanthemulide A (92) appears to be mediated via suppression of an LPS-induced NF-κB pathway and downregulation of MAPK activation [39,61]. In addition, using H9c2 cardiocytes impaired by lipopolysaccharide (LPS), compounds chrysanthguaianolactone D (65), 3α,4α,10β-trihydroxy-8α-acetoxyguai-1,11(13)-dien-6α,12-olide (67), 3α,4α,10β-trihydroxy-8α-acetoxy-11βH-guai-1-en-6α,12-olide (68), 8α-(angelyloxy)-3β,4β-dihydroxy-5αH,6βH,7αH,11αH-guai-1(10)-en-12,6-olide (71), and 3β,4α-dihydroxy-8α-angelyloxy-1(10),11(13)-dien-6β,12-olide (75) exhibited anti-inflammatory activity [33].…”

Section: Anti-inflammatory Activitymentioning

confidence: 99%

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Chemistry and Pharmacological Activity of Sesquiterpenoids from the Chrysanthemum Genus

et al. 2021

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Plants from the Chrysanthemum genus are rich sources of chemical diversity and, in recent years, have been the focus of research on natural products chemistry. Sesquiterpenoids are one of the major classes of chemical constituents reported from this genus. To date, more than 135 sesquiterpenoids have been isolated and identified from the whole genus. These include 26 germacrane-type, 26 eudesmane-type, 64 guaianolide-type, 4 bisabolane-type, and 15 other-type sesquiterpenoids. Pharmacological studies have proven the biological potential of sesquiterpenoids isolated from Chrysanthemum species, reporting anti-inflammatory, antibacterial, antitumor, insecticidal, and antiviral activities for these interesting molecules. In this paper, we provide information on the chemistry and bioactivity of sesquiterpenoids obtained from the Chrysanthemum genus which could be used as the scientific basis for their future development and utilization.

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Chrysanthemulide A induces apoptosis through DR5 upregulation via JNK‐mediated autophagosome accumulation in human osteosarcoma cells

Cited by 16 publications

References 57 publications

The genus Chrysanthemum: Phylogeny, biodiversity, phytometabolites, and chemodiversity

The genus Chrysanthemum: Phylogeny, biodiversity, phytometabolites, and chemodiversity

ASPP2 promotes cell apoptosis in cervical cancer through inhibiting autophagy

Chemistry and Pharmacological Activity of Sesquiterpenoids from the Chrysanthemum Genus

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