Clausenidin induces caspase-dependent apoptosis in colon cancer

Waziri, Peter; Abdullah, Rasedee; Yeap, Swee Keong; Omar, Abdul Rahman; Kassim, Nur Kartinee; Malami, Ibrahim; How, Chee Wun; Etti, Imaobong Christopher; Abu, Mary Ladidi

doi:10.1186/s12906-016-1247-1

Cited by 22 publications

(24 citation statements)

References 34 publications

(42 reference statements)

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“…Additionally, clausenidin ( Figure 2 ), obtained from the shrub Clausena excavate Burum.f. induced cell cycle arrest of colon cancer at the G0/G1 phase [ 32 ]. Similarly, cycleanine ( Figure 3 ) extracted from Triclisia subcordata Oliv., exerted the same effect as clausenidin on the cell cycle progression and induced G0/G1 immobilization of ovarian cancer cells [ 34 ].…”

Section: Emerging Cytotoxic Alkaloids: Apoptotic Strategmentioning

confidence: 99%

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

et al. 2017

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Considered as the second deadliest disease globally, cancer has captured the attention of researchers who have been trying with perseverance to decode its hidden aspects, to find new prognosis methods, and to develop better and more effective treatments. Plants have continuously offered an excess of unique secondary metabolites with remarkable biological applications. Alkaloids, one of the most abundant metabolites, constitute a large conglomerate of basic heterocyclic nitrogen-containing natural compounds which are normally produced by plants as toxic substances. Out of the 27,000 different alkaloids, more than 17,000 have displayed diversified pharmacological properties including anticancer activities. These metabolites have been classified either according to their chemical structures or their taxonomic origin. None of the researched alkaloids have been classified according to their molecular mechanism of action against cancer. In fact, only a fraction of the tremendous number of anticancer alkaloids has been copiously mentioned in journals. Here, we aim to provide a summary of the literature on some of the promising anticancer alkaloids that have not been well discussed previously and to classify them according to their molecular mechanisms of action. This review will provide a better understanding of the anticancer mechanisms of these promising natural products that are a rich reservoir for drug discovery.

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Section: Emerging Cytotoxic Alkaloids: Apoptotic Strategmentioning

confidence: 99%

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

et al. 2017

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“…The traditional use of Clausena excavata and its compounds for the treatment of cancer is based on Asian folklore that is devoid of scientific evidence. Previous study reported the anti-tumor properties of clausenidin isolated from the root of C. excavata (Waziri et al, 2016). However, the detailed mechanism of anti-cancer cell effect of clausenidin is poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…The clausenidin was isolated from the fresh roots of Clausena excavata (Voucher number, 2991/16) as described previously (Waziri et al, 2016). The IC50 of the pure clausenidin at 72 h was 13.8 ±2.89 µg/mL (Waziri et al, 2016).…”

Section: Extraction Of Clausenidinmentioning

confidence: 99%

“…Thus far, coumarins and alkaloids are the major bioactive components to have been isolated from C. excavata. Previous study reported that clausenidin (Figure 1) isolated from C. excavata induces caspase-dependent cell death in colon cancer cell line (Waziri et al, 2016). Since p53 is the most frequent mutated gene in cancerous cells, the current study investigates its role in clausenidin-treated HT-29 cells.…”

Section: Introductionmentioning

confidence: 97%

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Clausenidin upregulated p53 and caused apoptosis in HT-29 tumor cell lines

Waziri¹,

Abdullah²,

Rosli³

et al. 2018

Afr. J. Biotechnol.

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Clausenidin is a pyranocoumarin majorly found in medicinal herbs of the Rutaceae family used to treat cancer patients locally in Asia. The compound is presumed to have anti-cancer cell effect but its exact mechanism of action is still unknown. The study aimed to evaluate the effect of pure clausenidin on p53-mediated apoptosis as well as other cell death pathways in colon cancer (HT-29) cell lines. The antiproliferative effect of clausenidin by cell cycle and annexin V assay using flow cytometry was evaluated. Morphological analysis of the treated cells was performed using scanning and transmission electron microscopy. Furthermore, the effect of p53 mRNA on cell cycle and apoptosis-related genes and proteins in clausenidin-treated HT-29 cells was investigated using qPCR and Western blot assays, respectively. Clausenidin induced a p53 dependent G0/G1 cell cycle arrest in HT-29 cells. It was also observed that the anti-cancer cell effect of clausenidin occurred via p53 mediated activation of p21, bax and transrepression of survivin and bcl 2 that culminated in the apoptosis of colon cancer cells. The transmission electron microscopy (TEM) micrographs confirmed the occurrence of apoptosis in clausenidin-treated HT-29 cells. Clausenidin is a potent anti-HT-29 cell agent that can be used to treat colon tumors.

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“…Colorectal cancer is the second most common cause of cancer-related deaths; more than 1.4 million patients are diagnosed with colorectal cancer every year. 1 , 2 Tumor invasion and metastasis are the major cause of poor prognosis. 3 Nowadays, therapeutic methods for metastatic colorectal cancer are limited and insufficient.…”

Section: Introductionmentioning

confidence: 99%

Aurora-A Regulates Progression and Metastasis of Colorectal Cancer by Promoting Slug Activity

Li²,

Qin³

et al. 2016

Technol Cancer Res Treat

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Epithelial–mesenchymal transition (EMT) is associated with cancer metastasis and poor prognosis, but the exact mechanism has not been clarified. Centrosomal Aurora-A kinase gene is frequently overexpressed in a variety of cancers and plays a pivotal role in the growth and survival of cancer cells. However, its role in colorectal cancer metastasis has not been confirmed. Here we demonstrate that Aurora-A plays a crucial role in the progression and metastasis of colorectal cancer by regulating epithelial–mesenchymal transition. In our study, increased Aurora-A expression was detected in colorectal cancer clinical specimens compared to normal colorectal tissues. Moreover, overexpressed Aurora-A significantly promoted the proliferation, migration, and invasion capacity of colorectal cancer cells and then enhanced metastatic capacity of colorectal cancer in vitro and in vivo and eventually led to poor prognosis. Conversely, silencing Aurora-A expression in colorectal cancer cells decreased the capacity of proliferation, migration, and invasion and further reduced colorectal cancer metastasis. Mechanistically, we found that Slug was involved in Aurora-A–induced migration and invasion of colorectal cancer cells. Silencing Slug expression could block Aurora-A–induced migration, invasion, and metastasis of colorectal cancer cells. Furthermore, the expression of Aurora-A and Slug were positively correlated in colorectal cancer tissues and paired normal colorectal tissue. Taken together, our findings revealed a critical role of Aurora-A in colorectal cancer progression and metastasis by regulating epithelial–mesenchymal transition.

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Clausenidin induces caspase-dependent apoptosis in colon cancer

Cited by 22 publications

References 34 publications

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

Emerging Cytotoxic Alkaloids in the Battle against Cancer: Overview of Molecular Mechanisms

Clausenidin upregulated p53 and caused apoptosis in HT-29 tumor cell lines

Aurora-A Regulates Progression and Metastasis of Colorectal Cancer by Promoting Slug Activity

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