Emerging Anti-Mitotic Activities and Other  Bioactivities of Sesquiterpene Compounds  upon Human Cells

Bosco, Alessandra; Golsteyn, Roy M.

doi:10.3390/molecules22030459

Cited by 27 publications

(28 citation statements)

References 122 publications

(188 reference statements)

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“…Additionally, we have previously shown that C. minima ethanol extract (CME) could inhibit the proliferation of CNE-1 cells and activation of the PI3K–AKT–mTOR signaling pathway (Guo et al, 2015). Brevilin A is a single compound belonging to the SQL class of chemicals isolated from C. minima , with a variety of pharmacological activities (Liu et al, 2005; Chan et al, 2016; Bosco and Golsteyn, 2017). Previous studies have demonstrated the anti-cancer activity of SQLs isolated from C. minima in various cancers, including colon cancer (Huang et al, 2014), prostate cancer (Vishwanath Pradeep et al, 2012), and NPC (Su et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Zhao

Lin

et al. 2019

Front. Pharmacol.

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Nasopharyngeal carcinoma (NPC) is one of the most common malignant cancers in Southeast Asia and Southern China. Centipeda minima extract (CME) had previously demonstrated anti-cancer effects in human NPC. Brevilin A, a sesquiterpene lactone isolated from C. minima , has been reported to exhibit biological activities. In this study, we investigated its anti-NPC effect and further explored its molecular mechanisms. The effects of brevilin A were tested in the NPC cell lines CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. Effects of brevilin A on cell viability were determined by MTT assay, and cell cycle and apoptosis were detected by flow cytometry. The molecular mechanism of cell cycle regulation and apoptosis were investigated via Western blot. Results showed that brevilin A inhibited NPC cell viability in a concentration- and time-dependent manner. Brevilin A induced cell cycle arrest at G2/M and induced apoptosis. Western blot results demonstrated that brevilin A could down-regulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, while up-regulating cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by brevilin A showed dynamic changes according to dose and time. In the tumor xenograft model, brevilin A could reduce tumor growth, at a similar magnitude to cisplatin. However, notably, whereas cisplatin treatment led to significant weight loss in treated mice, treatment with brevilin A did not, indicating its relative lack of toxicity. Taken together, brevilin A regulated cell cycle, activated the caspase signaling pathway, and inhibited PI3K/AKT/mTOR and STAT3 signaling pathways in vitro , and exhibited similar efficacy to the common chemotherapeutic cisplatin in vivo , without its associated toxicity. These findings provide a framework for the preclinical development of brevilin A as a chemotherapeutic for NPC.

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Section: Discussionmentioning

confidence: 99%

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Zhao

Lin

et al. 2019

Front. Pharmacol.

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“…Brevilin A is a sesquiterpene lactone isolated from CM, and possesses a variety of pharmacological activities [13,14,36]. Arnicolide C and arnicolide D are also sesquiterpene lactones isolated from CM [1,12,13,32,33], however, relatively few studies have been conducted to investigate their biological activity.…”

Section: Discussionmentioning

confidence: 99%

Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma

Chan

Mok

et al. 2019

Molecules

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Nasopharyngeal carcinoma (NPC) is a high morbidity and mortality cancer with an obvious racial and geographic bias, particularly endemic to Southeast China. Our previous studies demonstrated that Centipeda minima extract (CME) exhibited anti-cancer effects in human NPC cell lines. Arnicolide C and arnicolide D are sesquiterpene lactones isolated from Centipeda minima. In this study, for the first time, we investigated their anti-NPC effects and further explored the related molecular mechanisms. The effects of both arnicolide C and arnicolide D were tested in NPC cells CNE-1, CNE-2, SUNE-1, HONE1, and C666-1. The results showed that the two compounds inhibited NPC cell viability in a concentration- and time-dependent manner. As the inhibitory effect of arnicolide D was the more pronounced of the two, our following studies focused on this compound. Arnicolide D could induce cell cycle arrest at G2/M, and induce cell apoptosis. The molecular mechanism of cell cycle regulation and apoptosis induction was investigated, and the results showed that arnicolide D could downregulate cyclin D3, cdc2, p-PI3K, p-AKT, p-mTOR, and p-STAT3, and upregulate cleaved PARP, cleaved caspase 9, and Bax. Regulation of cyclin B1, cdk6, and Bcl-2 expression by arnicolide D showed dynamic changes according to dose and time. Taken together, arnicolide D modulated the cell cycle, activated the caspase signaling pathway, and inhibited the PI3K/AKT/mTOR and STAT3 signaling pathways. These findings provide a solid base of evidence for arnicolide D as a lead compound for further development, and act as proof for the viability of drug development from traditional Chinese medicines.

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“…It phosphorylates and activates cell division cycle 25 (CDC25) to foster the exit from mitosis through activation of anaphase-promoting complex/cyclosome (APC/C) and the proteolytic machinery 4 . PLK1 is attached to the mitotic spindles through different stages of cell division 5 , which stabilizes the kinetochore–microtubule attachment and triggers the transition from meta- to anaphase 6 . PLK1 overexpression correlated with tumor progression and poor prognosis in different cancer types7., 8..…”

Section: Introductionmentioning

confidence: 99%

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

Abdelfatah

Berg

Huang

et al. 2019

Acta Pharmaceutica Sinica B

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Polo-like kinase (PLK1) has been identified as a potential target for cancer treatment. Although a number of small molecules have been investigated as PLK1 inhibitors, many of which showed limited selectivity. PLK1 harbors a regulatory domain, the Polo box domain (PBD), which has a key regulatory function for kinase activity and substrate recognition. We report on 3-bromomethyl-benzofuran-2-carboxylic acid ethyl ester (designated: MCC1019) as selective PLK1 inhibitor targeting PLK1 PBD. Cytotoxicity and fluorescence polarization-based screening were applied to a library of 1162 drug-like compounds to identify potential inhibitors of PLK1 PBD. The activity of compound MC1019 against the PLK1 PBD was confirmed using fluorescence polarization and microscale thermophoresis. This compound exerted specificity towards PLK1 over PLK2 and PLK3. MCC1019 showed cytotoxic activity in a panel of different cancer cell lines. Mechanistic investigations in A549 lung adenocarcinoma cells revealed that MCC1019 induced cell growth inhibition through inactivation of AKT signaling pathway, it also induced prolonged mitotic arrest—a phenomenon known as mitotic catastrophe, which is followed by immediate cell death via apoptosis and necroptosis. MCC1019 significantly inhibited tumor growth in vivo in a murine lung cancer model without affecting body weight or vital organ size, and reduced the growth of metastatic lesions in the lung. We propose MCC1019 as promising anti-cancer drug candidate.

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Emerging Anti-Mitotic Activities and Other Bioactivities of Sesquiterpene Compounds upon Human Cells

Cited by 27 publications

References 122 publications

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Brevilin A Induces Cell Cycle Arrest and Apoptosis in Nasopharyngeal Carcinoma

Arnicolide D, from the herb Centipeda minima, Is a Therapeutic Candidate against Nasopharyngeal Carcinoma

MCC1019, a selective inhibitor of the Polo-box domain of Polo-like kinase 1 as novel, potent anticancer candidate

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