The use of natural products in colorectal cancer drug discovery

Miura, Koh; Satoh, Masayuki; Kinouchi, Makoto; Yamamoto, Kuniharu; Hasegawa, Yasuhiro; Kakugawa, Yoichiro; Kawai, Masaaki; Uchimi, Kiyoshi; Aizawa, Hiroki; Ohnuma, Shinobu; Kajiwara, Taiki; Sakurai, Hiroto; Fujiya, Tsuneaki

doi:10.1517/17460441.2015.1018174

Cited by 20 publications

(13 citation statements)

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“…Numerous studies have reported the anticancer effects of herbal medicines or phytochemicals for the treatment of CRC. Herbal medicines may have improved efficacy and safety compared to other regimens as well as the potential to be used as a complementary therapy for advanced colorectal adenocarcinoma and mCRC [10][11][12]. Examples of current clinically used phytochemicals include Catharanthus alkaloids (Vinca rosea) [13] and Camptotheca (happy tree, cancer tree) [14], while others are currently in clinical trials such as curcumin, green tea and soybeans [15].…”

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confidence: 99%

Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling

et al. 2020

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Background: Colorectal carcinoma is one of the most deadly cancers that requests effective and safe chemotherapy. Evaluation of natural product-based anticancer drugs as adjuvant treatment with fewer side effects is largely unexplored research fields. Herbal melanin (HM) is an extract of the seed coats of Nigella sativa that modulates an inflammatory response through toll-like receptor 4 (TLR4). This TLR4 receptor is also involved in the modulation of apoptosis. We therefore explored the anticancer potential of HM and specifically its effect on the molecular mechanisms underlying adenocarcinoma and metastatic colorectal cancer (mCRC) cell death in vitro. Methods:Cell viability was evaluated using the MTT assay. Cellular reactive oxygen species (ROS), glutathione levels, and apoptotic status were assessed using fluorometric and colorimetric detection methods. HM-induced apoptotic and other signaling pathways were investigated using Western blot technology and mitochondrial transition pore assay kit. TLR4 receptor downregulation and blockade were performed using siRNA technology and neutralizing antibody, respectively. Results:Our results showed that HM inhibited the proliferation of the colorectal adenocarcinoma HT29 and mCRC SW620 cell lines. Furthermore, HM enhanced ROS production and decreased glutathione levels. HM-induced apoptosis was associated with mitochondrial outer membrane permeability and cytochrome c release, inhibition of the Bcl2 family proteins, and activation of caspase-3/-7. In addition, HM modulated MAPK pathways by activating the JNK pathway and by inhibiting ERK phosphorylation. TLR4 receptor downregulation enhanced HM-induced apoptosis while TLR4 receptor blockade partially alleviated HM-inhibited ERK phosphorylation. Conclusion:Altogether, these findings indicate that HM exerts pro-apoptotic effects and inhibits MAPK pathway through TLR4 in mCRC and colorectal adenocarcinoma cells, suggesting HM as a promising natural-based drug for the treatment of colorectal cancer.

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confidence: 99%

Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling

et al. 2020

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“…According to national cancer registry (NCR) report of Malaysia, CRC was the second most common cancer diagnosed during the year 2007 (Ariffin and Saleha, 2011;Asif et al, 2016b), which highlights the need to find new treatment strategies to manage this life threatening ailment. In the recent years extensive research has been conducted on natural products to find new drug moieties that can be used safely for the prevention and treatment of CRC (Miura et al, 2015). Present study describes the molecular mechanisms responsible for in vitro cytotoxic attributes of terpenes richfraction (F-3) towards human colon carcinoma HCT 116 cells.…”

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confidence: 98%

Molecular mechanisms responsible for programmed cell death-inducing attributes of terpenes from Mesua ferrea stem bark towards human colorectal carcinoma HCT 116 cells

et al. 2017

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The current study explored the in vitro anticancer properties of Mesua ferrea stem bark (SB) extract towards human colon carcinoma HCT116 cells. SB was successively extracted with different solvents using soxhlet apparatus. MTT assay was employed to test toxicity against different cancer and normal cell lines. Active extract (n-Hexane) was fractionated by column chromatography (CC) to get the most active fraction (F-3). Series of in vitro assays were employed to characterize cytotoxic nature of F-3. Antioxidant properties of F-3 were assessed using DPPH, ABTS and FRAP assays followed by GC-MS analysis. Intracellular ROS levels were measured by DCFH-DA fluorescent assay. Finally, cell signalling pathways and their downstream proteins targeted by F-3 were studied using 10-cancer pathway and human apoptosis protein profilers and in silico docking studies. n-Hexane extract and its fraction (F-3) showed potent anti-proliferative effect against HCT 116. Programmed cell death (PCD) studies showed that F-3 modulated the expression of multiple proteins in HCT 116. F-3 showed weak antioxidant activity in all the models, while significant increase in ROS was observed in HCT 116. GC-MS analysis revealed that F-3 was majorly comprised of terpenes. Data of pathway profiler and in silico studies revealed that F-3 downregulated the expression of NF-kB and HIF-1a pathways. Overall these results demonstrate that anticancer effects of M. ferrea stem bark towards human colon carcinoma are mainly due to its terpenes contents.

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“…Identifying strategies to fight against CRC is important, as it is an emerging health problem. It is now well documented that phytochemicals, including flavonoids, alkaloids and polysaccharides, are important in anticancer therapy ( 2 , 3 ).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effect of hyperoside isolated from Zanthoxylum bungeanum leaves on SW620 human colorectal cancer cells via induction of the p53 signaling pathway and apoptosis

Zhang

Dong

Zhang

et al. 2017

Molecular Medicine Reports

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The present study aimed to demonstrate the antiproliferative effect of hyperoside from Zanthoxylum bungeanum leaves (HZL) and explain the underlying molecular mechanisms in the SW620 human colorectal cancer cell line. The cytotoxic effects of HZL were determined using a3-(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide assay. Apoptosis and cell cycle were detected using flow cytometry. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (∆Ψm) were assessed using 2′,7′-dichlorofluorescin diacetate and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolyl carbocyanine iodide fluorescence spectrophotometry, respectively. Western blot analysis was used to quantify the expression levels of apoptosis-associated proteins. Reverse transcription-quantitative polymerase chain reaction analysis was used to determine the mRNA expression of glutathione peroxidase (GSH-Px) and catalase (CAT). HZL had a marked anti-proliferative effect on the SW620 human colorectal cancer cells by inducing cell cycle G2/M phase arrest and apoptosis, which was associated with an increase in the expression of p53 and p21. Further mechanistic investigations revealed that the induction of apoptosis was associated with increased generation of ROS, reduced ∆Ψm, and upregulation of B-cell lymphoma 2-associated X protein, cytochrome c, caspase-9, apoptotic protease activating factor 1 and caspase-3. The antitumor potency of HZL was also attributed to inhibition of the mRNA expression levels of GSH-Px and CAT. These data indicated that HZL may be involved in the pro-apoptotic signaling of SW620 human colorectal cancer cells via induction of the caspase-dependent apoptosis and p53 signaling pathways.

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The use of natural products in colorectal cancer drug discovery

Abstract: The use of NPs for the discovery of anti-cancer agents has not been fully investigated. New technologies that are currently applied for synthetic compounds may be utilized for anti-cancer drug discovery including NPs for CRC.

Cited by 20 publications

References 92 publications

Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling

Herbal melanin inhibits colorectal cancer cell proliferation by altering redox balance, inducing apoptosis, and modulating MAPK signaling

Molecular mechanisms responsible for programmed cell death-inducing attributes of terpenes from Mesua ferrea stem bark towards human colorectal carcinoma HCT 116 cells

Inhibitory effect of hyperoside isolated from Zanthoxylum bungeanum leaves on SW620 human colorectal cancer cells via induction of the p53 signaling pathway and apoptosis

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