Novel Marine Secondary Metabolites Worthy of Development as Anticancer Agents: A Review

Secondary metabolites from marine sources have a wide range of biological activity. Marine natural products are promising candidates for lead pharmacological compounds to treat diseases that plague humans, including cancer. Cancer is a life-threatening disorder that has been difficult to overcome. It is a long-term illness that affects both young and old people. In recent years, significant attempts have been made to identify new anticancer drugs, as the existing drugs have been useless due to resistance of the malignant cells. Natural products derived from marine sources have been tested for their anticancer activity using a variety of cancer cell lines derived from humans and other sources, some of which have already been approved for clinical use, while some others are still being tested. These compounds can assault cancer cells via a variety of mechanisms, but certain cancer cells are resistant to them. As a result, the goal of this review was to look into the anticancer potential of marine natural products or their derivatives that were isolated from January 2019 to March 2020, in cancer cell lines, with a focus on the class and type of isolated compounds, source and location of isolation, cancer cell line type, and potency (IC50 values) of the isolated compounds that could be a guide for drug development.

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Recombinant deoxyribonucleoside kinase from Drosophila melanogaster can improve gemcitabine based combined gene/chemotherapy for targeting cancer cells

Bosnian Journal of Basic Medical Sciences ◽

10.17305/bjbms.2019.4136 ◽

2019 ◽

Author(s):

Mahak Fatima ◽

M. Mubasshar Iqbal Ahmed ◽

Faiza Batool ◽

Anjum Riaz ◽

Moazzam Ali ◽

...

Keyword(s):

Drosophila Melanogaster ◽

Cancer Cells ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Line ◽

Nucleoside Analogs ◽

Cancer Cell Lines ◽

Control Group ◽

Wide Range

A recombinant deoxyribonucleoside kinase from Drosophila melanogaster with a deletion of the last 20 amino acid residues (named DmdNKΔC20) was hypothesized as a potential therapeutic tool for gene therapy due to its broad substrate specificity and better catalytic efficiency towards nucleosides and nucleoside analogs. This study was designed to evaluate the effect of DmdNKΔC20 for sensitizing human cancer cell lines towards gemcitabine and to further investigate its role in reversal of acquired drug resistance in gemcitabine-resistant cancer cell line. The DmdNKΔC20 gene was delivered to three different cancer cell lines, including breast, colon and liver cancer cells, using lipid-mediated transfection reagent. After transfection, gene expression of DmdNKΔC20 was confirmed by reverse transcription quantitative PCR (qRT-PCR) and the combined effect of DmdNKΔC20 and gemcitabine based cytotoxicity was observed by cell viability assay. We further evolved a gemcitabine-resistant breast cancer cell line (named MCF7-R) through directed evolution in the laboratory, which showed 375-fold more resistance compared to parental MCF7 cells. Upon transfection with DmdNKΔC20 gene, MCF7-R cells showed 83-fold higher sensitivity to gemcitabine compared to the control group of MCF7-R cells. Moreover, we observed 79% higher expression of p21 protein in transfected MCF7-R cells, which may indicate induction of apoptosis. Our findings highlight the importance and therapeutic potential of DmdNKΔC20 in combined gene/chemotherapy approach to target a wide range of cancers, particularly gemcitabine-resistant cancers.

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Epithelial-to-Mesenchymal Transition Is Not a Major Modulating Factor in the Cytotoxic Response to Natural Products in Cancer Cell Lines

Molecules ◽

10.3390/molecules26195858 ◽

2021 ◽

Vol 26 (19) ◽

pp. 5858

Author(s):

Baris Kucukkaraduman ◽

Ekin Gokce Cicek ◽

Muhammad Waqas Akbar ◽

Secil Demirkol Canli ◽

Burcak Vural ◽

...

Keyword(s):

Natural Products ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Epithelial To Mesenchymal Transition ◽

Epigallocatechin Gallate ◽

Cancer Cell Lines ◽

Vimentin Expression ◽

Mesenchymal Transition ◽

Urolithin A

Numerous natural products exhibit antiproliferative activity against cancer cells by modulating various biological pathways. In this study, we investigated the potential use of eight natural compounds (apigenin, curcumin, epigallocatechin gallate, fisetin, forskolin, procyanidin B2, resveratrol, urolithin A) and two repurposed agents (fulvestrant and metformin) as chemotherapy enhancers and mesenchymal-to-epithelial (MET) inducers of cancer cells. Screening of these compounds in various colon, breast, and pancreatic cancer cell lines revealed anti-cancer activity for all compounds, with curcumin being the most effective among these in all cell lines. Although some of the natural products were able to induce MET in some cancer cell lines, the MET induction was not related to increased synergy with either 5-FU, irinotecan, gemcitabine, or gefitinib. When synergy was observed, for example with curcumin and irinotecan, this was unrelated to MET induction, as assessed by changes in E-cadherin and vimentin expression. Our results show that MET induction is compound and cell line specific, and that MET is not necessarily related to enhanced chemosensitivity.

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8-Hydroxycudraxanthone G Suppresses IL-8 Production in SP-C1 Tongue Cancer Cells

Natural Product Communications ◽

10.1177/1934578x1400900122 ◽

2014 ◽

Vol 9 (1) ◽

pp. 1934578X1400900

Author(s):

Arlette S. Setiawan ◽

Roosje R. Oewen ◽

Supriatno ◽

Willyanti Soewondo ◽

Sidik ◽

...

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Therapeutic Intervention ◽

Tongue Cancer ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Garcinia Mangostana ◽

Anti Cancer ◽

Cancer Activity

Production of IL-8 primarily promotes angiogenic responses in cancer cells, which lead to favorable disease progression. Suppressing this production may, therefore, be a significant therapeutic intervention in targeting tumor angiogenesis. This study aimed to evaluate the reduction effects of xanthones in cancer cell lines. Nine known prenylated xanthones (1–9), isolated from the pericarp of Garcinia mangostana Linn (GML), were tested for their ability to suppress IL-8 (interleukin-8) of the SP-C1 (Supri's Clone 1) tongue cancer cell line. Of these compounds, 8-hydroxycudraxanthone-G (4) suppressed IL-8 within 48 hours. This is the first report of 8-hydroxycudraxanthone G suppressing the production of IL-8 (45% at 15.7 μg/mL in 48 hours). These results suggest that the prolonged suppression of IL-8 production by cancer cell lines is concerned in the anti-cancer activity of 8-hydroxycudraxanthone.

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ETHNOPHARMACOLOGICAL EVALUATION OF MEDICINAL PLANTS FOR CYTOTOXICITY AGAINST VARIOUS CANCER CELL LINES

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2017v9i5.17289 ◽

2017 ◽

Vol 9 (5) ◽

pp. 198 ◽

Cited By ~ 1

Author(s):

Ruchi Singh Thakur ◽

Bharti Ahirwar

Keyword(s):

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Fruit Juice ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Phytochemical Analysis ◽

Phyllanthus Emblica ◽

Hydroalcoholic Extract

Objective: To evaluate the cytotoxic potential of leaves and seeds of Hibiscus sabdariffa L., fruit juice of Phyllanthus emblica, rhizomes of Dryopteris cochleata and flowers of Caesalpinia decapetala (Roth) Alston along with the chemical profiling of the most toxic extract through Gas-mass spectroscopy-MS technique.Methods: The hydroalcoholic extract of the selected crude drugs was prepared by maceration method and the extracts were undergone through phytochemical analysis. The cytotoxic activity of the hydroalcoholic extract was performed against four cancer cell lines i.e. liver (HepG2), breast (MCF7), prostate (PC-3) and leukemia (HL60) using sulphorhodamine B assay. The hydroalcoholic extract of Caesalpinia decapetala flowers was profiled through using gas mass spectroscopy.Results: The results confirmed that Phyllanthus emblica inhibited HL60 cancer cells at the dose of 35.6 µg/ml and show dose-dependent growth inhibition. The flowers of Caesalpinia decapetala inhibited nearly fifty percent of HL60 cancer cells at very low dose i. e 10 µg/ml. The analysis of Caesalpinia decapetala flowers shows the presence of diterpenoid furanolactones, bufadienolides, polycyclic enones, and androsterone.Conclusion: The fruit juice of Phyllanthus emblica and flowers of Caesalpinia decapetala showed good inhibitory activity against HL60 cancer cell line. The use of Phyllanthus emblica in herbal medicine is justified. The data obtained impelled to further assess the in vivo efficacy of Caesalpinia decapetala flowers for anticancer activity.

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Secondary Metabolites of Saussurea costus Leaf Extract Induce Apoptosis in Breast, Liver, and Colon Cancer Cells by Caspase-3-Dependent Intrinsic Pathway

BioMed Research International ◽

10.1155/2020/1608942 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Ali A. Shati ◽

Mohammed A. Alkahtani ◽

Mohamed Y. Alfaifi ◽

Serag Eldin I. Elbehairi ◽

Fahmy G. Elsaid ◽

...

Keyword(s):

Secondary Metabolites ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agent ◽

Cancer Cell Lines ◽

Chemotherapeutic Agents ◽

Expression Level ◽

Intrinsic Pathway ◽

Anticancer Effect

Background. Apoptosis, a major form of programmed cell death, plays a vital role in regulating tissue development and maintenance of homeostasis in eukaryotes. Apoptosis can occur via a death receptor-dependent extrinsic or a mitochondrial-dependent intrinsic pathway and can be induced by various chemotherapeutic agents. In this study, the anticancer activity of Saussurea costus and its mode of intervention in human cancer cells of breast, colon, and liver were investigated. Results. In this study, the bioactives of S. costus leaves were extensively extracted in five solvents of different polarity. The cytotoxicity and anticancer effect of the extracted secondary metabolites were investigated against breast (MCF-7), liver (HepG2), and colon (HCT116) cancer cell lines using a Sulphorhodamine B (SRB) assay. Secondary metabolites extracted using hexane, methanol, ethyl acetate, and chloroform had the highest cytotoxicity and thus the greatest anticancer effect on all the cancer cell lines tested (IC50; ranging from 0.25 to 2.5 μg/ml), while butanol was comparatively less active (IC50; ranging from 23.2 to 25.5 μg/ml). Further investigation using DNA flow cytometry and fluorescent microscopy revealed that the extract arrested the cells in the G1 phase of cell cycle and induced apoptosis. Furthermore, the elevated expression level of proapoptotic proteins and decreased expression level of antiapoptotic proteins confirmed that the intrinsic (mitochondrial) pathway was involved in mediating the apoptosis of cancer cells upon treatment with S. costus extract. These results altogether suggest that S. costus could be a potential anticancer agent. Conclusion. These results suggest that the S. costus extract is the potential source of the secondary metabolites that could be used as anticancer agent to treat diverse cancers of breast, colon, and liver.

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P16 methylation increases the sensitivity of cancer cells to the CDK4/6 inhibitor palbociclib

10.1101/771337 ◽

2019 ◽

Author(s):

Paiyun Li ◽

Xuehong Zhang ◽

Liankun Gu ◽

Jing Zhou ◽

Dajun Deng

Keyword(s):

Dna Methylation ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Copy Number ◽

Dna Methyltransferase ◽

Gastric Cancer Cell Line ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Gene Copy

AbstractThe P16 (CDKN2Aink4a) gene is an endogenous CDK4/6 inhibitor. Palbociclib (PD0332991) is an anti-CDK4/6 chemical for cancer treatment. P16 is most frequently inactivated by copy number deletion and DNA methylation in cancers. It is well known that cancer cells with P16 deletion are more sensitive to palbociclib than those without. However, whether P16 methylation is related to palbociclib sensitivity is not known. By analyzing public pharmacogenomic datasets, we found that the IC50 of palbociclib in cancer cell lines (n=522) was positively correlated with both the P16 expression level and P16 gene copy number. Our experimental results further showed that cancer cell lines with P16 methylation were more sensitive to palbociclib than those without. To determine whether P16 methylation directly increased the sensitivity of cancer cells to palbociclib, we induced P16 methylation in the lung cancer cell lines H661 and HCC827 and the gastric cancer cell line BGC823 via an engineered P16-specific DNA methyltransferase (P16-Dnmt) and found that the sensitivity of these cells to palbociclib was significantly increased. The survival rate of P16-Dnmt cells was significantly lower than that of vector control cells 48 hrs post treatment with palbociclib (10 μM). Notably, palbociclib treatment also selectively inhibited the proliferation of the P16-methylated subpopulation of P16-Dnmt cells, further indicating that P16 methylation can increase the sensitivity of cells to this CDK4/6 inhibitor. These results were confirmed in an animal experiment. In conclusion, inactivation of the P16 gene by DNA methylation can increase the sensitivity of cancer cells to palbociclib.

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In vitro Anticancer Activity of Marine Sponges Against T47D and HeLa Cell Lines

Dhaka University Journal of Pharmaceutical Sciences ◽

10.3329/dujps.v19i1.47815 ◽

2020 ◽

Vol 19 (1) ◽

pp. 25-28

Author(s):

Suciati ◽

Lusiana Arifianti

Keyword(s):

Anticancer Activity ◽

Cancer Cells ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Cancer Cell Line ◽

Marine Sponges ◽

Hela Cell Lines

Marine sponges have been known as the source of natural products. Various metabolites with potent bioactivities have been reported from this organism. The current study aims to investigate the anticancer potency of three marine sponges namely Diacarnus debeauforti, Haliclona amboinensis and Agelas cavernosa collected from Barrang Lompo Island, South Sulawesi, Indonesia. The ethyl acetate extracts of the sponges were screened against T47D breast cancer cells and HeLa cervical cancer cells by using the MTT method. The results showed that these sponges demonstrated anticancer activity against both cancer cell lines. The lowest IC50 of 18.2 μg/ml was given by the extract of A. cavernosa against T47D cell line, while in the screening against HeLa cancer cell line, the extract of D. debeauforti revealed the highest potency with IC50 of 15.7 μg/ml. Our results suggested that the marine sponges namely D. debeauforti, H. amboinensis and A. cavernosa can be good candidates for the development of anticancer agents. Dhaka Univ. J. Pharm. Sci. 19(1): 25-28, 2020 (June)

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Autophagy inhibition enhances Matrine derivative MASM induced apoptosis in cancer cells via a mechanism involving reactive oxygen species-mediated PI3K/Akt/mTOR and Erk/p38 signaling

BMC Cancer ◽

10.1186/s12885-019-6199-7 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 1

Author(s):

Yuming Zou ◽

Melika Sarem ◽

Shengnan Xiang ◽

Honggang Hu ◽

Weidong Xu ◽

...

Keyword(s):

Reactive Oxygen Species ◽

Cancer Cells ◽

Cell Line ◽

Cell Lines ◽

Cancer Cell ◽

Reactive Oxygen ◽

Cancer Cell Line ◽

Cancer Cell Lines ◽

Oxygen Species ◽

Induced Apoptosis

Abstract Background In the quest for new anti-cancer drugs, the drug discovery process has shifted to screening of active ingredients in traditional eastern medicine. Matrine is an active alkaloid isolated from plants of the Sophora genus used in traditional Chinese herbal medicine that exhibits a wide spectrum of biological properties and has a potential as an anti-proliferative agent. In this study, we investigated the anticancer property of MASM, ([(6aS, 10S, 11aR, 11bR, 11cS)210-Methylamino-dodecahydro-3a, 7a-diaza-benzo (de)anthracene-8-thione]), a potent derivative of matrine. Methods Four epithelial cancer cell lines representing the dominant cancers, namely: A549 (non-small-cell lung cancer cell line), MCF-7 and MDA-MB-231 (breast cancer cell lines), and Hela (cervical cancer cell line) were employed, and the mechanistic underpinning of MASM-induced apoptosis was investigated using flow cytometry, western blot and immunofluorescence. Results MASM, induced apoptosis via caspase 3 dependent and independent pathways, and autophagy in all the four cancer cell lines, but post-EMT (epithelial mesenchymal transition) cells showed greater sensitivity to MASM. Scavenging reactive oxygen species using N-acetylcysteine rescued all cancer cell lines from apoptosis and autophagy. Mechanistic analysis revealed that MASM induced autophagy involves inhibition of Akt signaling and the activation of Erk and p38 signaling, and inhibition of autophagy further enhanced the apoptosis induced by MASM. Conclusions These results indicate that MASM possesses potency against cancer cells and modulating autophagy during MASM administration could be used to further enhance its therapeutic effects.

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Multi-Component Reactions of Cyclohexan-1,3-dione: Synthesis of Fused Pyran, Pyridine, Thiophene and Pyrazole Derivatives with c-Met, AntiProliferative Activities

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210112115128 ◽

2021 ◽

Vol 21 ◽

Author(s):

Rafat M. Mohareb ◽

Amira M. Elmetwally ◽

Abeer A. Mohamed

Keyword(s):

Prostate Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Prostate Cancer Cell ◽

Cancer Cell Line ◽

Prostate Cancer Cell Line ◽

Heterocyclic Ring ◽

Cancer Cell Lines ◽

Wide Range ◽

Target Molecules

Background: Recently products of multi-component reactions (MCR’s) acquired a special attention due to their wide range of pharmacological activities especially the therapeutic activities. Through the market it was found that many pharmacological drugs containing the pyran and pyridine nucleus that were produced through MCR’s were known. Objective: We are aiming in this work to synthesize target molecules not only possess anti-tumour activities but also cMet and prostate cancer inhibitors. The target molecules were obtained starting from cyclohexan-1,3-dione through its multi-component reactions to produce anticancer target molecules. Methods: Cyclohexan-1,3-dione underwent different multi-component reactions to produce fused pyran, pyridine and thiophene derivatives. The anti-proliferative activity of the newly synthesized compounds among the synthesized compounds toward the six cancer cell lines namely A549, H460, HT-29, MKN-45, U87MG, and SMMC-7721 was studied. In addition, inhibitions toward c-Met kinase and prostate cancer cell line were studied. Antitumor evaluations toward seventeen cancer cell lines subpanel according the diseases, for certain compounds were also demonstrated. Pim-1 kinase inhibitions of the most active compounds were also measured. Results: Anti-proliferative evaluations, c-Met and Pim-1 kinase inhibitions were performed for most of the synthesized compounds where the varieties of substituent through the aryl ring and the heterocyclic ring afforded compounds with high activities. Conclusion: Compounds 4b, 6b, 8b, 9a, 11b, 12b, 17b, 18b, 19, 22c, 23b and 25b were the most cytotoxic compounds toward the six cancer cell lines. Inhibitions toward c-Met kinase and prostate cancer cell showed that the presence of the electronegative Cl group within the molecule was responsible for its high activity. In addition, inhibitions toward Pim-1 kinase exhibited that most of tested compounds showed high inhibitions.

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Indoles as anticancer agents

Advances in Modern Oncology Research ◽

10.18282/amor.v1.i1.12 ◽

2015 ◽

Vol 1 (1) ◽

pp. 20 ◽

Cited By ~ 26

Author(s):

Mardia T El-sayed ◽

Nehal A Hamdy ◽

Dalia A Osman ◽

Khadiga M Ahmed

Keyword(s):

Cell Death ◽

Natural Products ◽

Anticancer Activity ◽

Cell Lines ◽

Cancer Cell ◽

Anticancer Agents ◽

Drug Approval ◽

Cancer Cell Lines ◽

Induce Cell Death ◽

Related Compounds

Indoles are natural products well known for their anticancer activity, which is related to their ability to induce cell death for many cancer cell lines. This review addresses indoles as natural products, mechanism of indoles, facilitated induction and recent studies with indoles and related compounds that were investigated via anticancer screening and that led to drug approval.

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