Novel approaches for identification of anti-tumor drugs and new bioactive compounds

Kawada, Manabu; Atsumi, Saoko; Wada, Shun‐ichi; Sakamoto, Shuichi

doi:10.1038/ja.2017.97

Cited by 9 publications

(12 citation statements)

References 27 publications

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“…Despite extensive efforts to develop highly efficient chemotherapeutic molecules, the vast majority of candidate drugs, including several classes of HSP90 inhibitors, have, so far, failed approval by the U.S. Food and Drug Administration ( 56 ). Based on our earlier and present studies, we reason that variability in results could have resulted from drug administration at inconsistent phases of either the tumor or host circadian rhythms ( 15 ).…”

Section: Discussionmentioning

confidence: 99%

Time-of-day specificity of anticancer drugs may be mediated by circadian regulation of the cell cycle

et al. 2021

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Circadian rhythms are an integral part of physiology, underscoring their relevance for the treatment of disease. We conducted cell-based high-throughput screening to investigate time-of-day influences on the activity of known antitumor agents and found that many compounds exhibit daily rhythms of cytotoxicity concomitant with previously reported oscillations of target genes. Rhythmic action of HSP90 inhibitors was mediated by specific isoforms of HSP90, genetic perturbation of which affected the cell cycle. Furthermore, clock mutants affected the cell cycle in parallel with abrogating rhythms of cytotoxicity, and pharmacological inhibition of the cell cycle also eliminated rhythmic drug effects. An HSP90 inhibitor reduced growth rate of a mouse melanoma in a time-of-day–specific manner, but efficacy was impaired in clock-deficient tumors. These results provide a powerful rationale for appropriate daily timing of anticancer drugs and suggest circadian regulation of the cell cycle within the tumor as an underlying mechanism.

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Section: Discussionmentioning

confidence: 99%

Time-of-day specificity of anticancer drugs may be mediated by circadian regulation of the cell cycle

et al. 2021

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“…16 Since the toxicity of and tolerance to conventional antitumor drugs greatly limit the treatment outcomes of HCC, natural bioactive substances have become a substitute with great therapeutic potential. 7 Until now, obvious antitumor effects in HCC have been identified in diverse natural bioactive substances, such as gambogic acid, tea catechins, genistein, berberine, resveratrol, curcumin, artemisinin, and matrine. 17 In this study, the antitumor roles of laminarin, a polysaccharide in seaweed, were evaluated.…”

Section: Discussionmentioning

confidence: 99%

“…Due to the adverse effects of and drug resistance to conventional antitumor drugs, natural bioactive substances emerge as potential sources of antitumor drugs with low toxicity. 7 Laminarin (1-3,1-6-glucan) is a polysaccharide in seaweed (Laminaria japonica) that is composed of 1,3-and 1,6-glycosidic bond-linked b-D-glucopyranose molecules. Laminarin exhibits bioactivities similar to those of b-glucan, such as immune-enhancing, antioxidant, anti-aging, and antitumor properties.…”

Section: Introductionmentioning

confidence: 99%

Laminarin from Seaweed (Laminaria japonica) Inhibits Hepatocellular Carcinoma Through Upregulating Senescence Marker Protein-30

Lin

et al. 2020

Cancer Biotherapy and Radiopharmaceuticals

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Objective: This study aimed at investigating the specific roles of laminarin from seaweed (Laminaria japonica) in hepatocellular carcinoma (HCC) and its potential mechanisms related to senescence marker protein-30 (SMP-30). Materials and Methods: Human HCC cell lines, including Bel-7404 and HepG2, were incubated with different concentrations of laminarin (0, 5, 15, 25, 35, and 45 mg/mL). The cell viability and apoptosis rates were detected by WST-8 cell proliferation assay and flow cytometry, respectively. Hepa 1-6 tumor-bearing mice were injected with different concentrations of laminarin (400, 800, and 1200 mg/kg$d), and tumor volume and weight were measured. The expression of SMP-30 was detected in laminarin-treated Bel-7404 and HepG2 HCC cells and LO2 normal liver cells by quantitative real-time PCR and Western blotting. Results: The treatment with laminarin (48 h) significantly decreased the viability and increased the apoptosis rates of Bel-7404 and HepG2 cells in a dose-dependent manner. The injection of laminarin also significantly decreased the tumor volumes (beginning on the 10th day) and tumor weights (30 d post-injection) of mice in a dose-dependent manner. In addition, the treatment with laminarin (35 mg/mL for 48 h) significantly upregulated SMP-30 in Bel-7404 and HepG2 cells but not in LO2 cells. Conclusion: Laminarin inhibited the proliferation of Bel-7404 and HepG2 cells and inhibited the growth of tumors in Hepa 1-6 tumor-bearing mice by upregulating SMP-30.

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“…With the continuous advancement of the lifestyle changes, it is necessary to extract new molecules, which can be potentially used for disease prevention and to find new drugs which may be crucial for cancer patient survival. The natural compounds are extracted in part from vegetal [27], microbial [28], and marine species [29] (Figure 1). Each of these can widely be used as a major source of activities against cancer and other diseases such as diabetes [30], cardiovascular diseases [31], liver diseases [32], asthma [33], neurodegenerative diseases [34], osteoporosis [35], anemia [36], bulimia [37], influenza/ pneumonia [38], renal and thyroid disorders [39,40], nephritis [41], periodontal (gum) disease [42], hypertension [43] and skin disorders [44] (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Combinatorial Epigenetics Impact of Polyphenols and Phytochemicals in Cancer Prevention and Therapy

Arora

Sharma

Tollefsbol

2019

IJMS

153

122

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Polyphenols are potent micronutrients that can be found in large quantities in various food sources and spices. These compounds, also known as phenolics due to their phenolic structure, play a vital nutrient-based role in the prevention of various diseases such as diabetes, cardiovascular diseases, neurodegenerative diseases, liver disease, and cancers. However, the function of polyphenols in disease prevention and therapy depends on their dietary consumption and biological properties. According to American Cancer Society statistics, there will be an expected rise of 23.6 million new cancer cases by 2030. Due to the severity of the increased risk, it is important to evaluate various preventive measures associated with cancer. Relatively recently, numerous studies have indicated that various dietary polyphenols and phytochemicals possess properties of modifying epigenetic mechanisms that modulate gene expression resulting in regulation of cancer. These polyphenols and phytochemicals, when administrated in a dose-dependent and combinatorial-based manner, can have an enhanced effect on epigenetic changes, which play a crucial role in cancer prevention and therapy. Hence, this review will focus on the mechanisms of combined polyphenols and phytochemicals that can impact various epigenetic modifications such as DNA methylation and histone modifications as well as regulation of non-coding miRNAs expression for treatment and prevention of various types of cancer.

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Novel approaches for identification of anti-tumor drugs and new bioactive compounds

Cited by 9 publications

References 27 publications

Time-of-day specificity of anticancer drugs may be mediated by circadian regulation of the cell cycle

Time-of-day specificity of anticancer drugs may be mediated by circadian regulation of the cell cycle

Laminarin from Seaweed (Laminaria japonica) Inhibits Hepatocellular Carcinoma Through Upregulating Senescence Marker Protein-30

Combinatorial Epigenetics Impact of Polyphenols and Phytochemicals in Cancer Prevention and Therapy

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