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Phytochemicals in Cancer Prevention and Therapy

BioMed Research International

December 2015
2015:1-2

DOI:10.1155/2015/324021

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Authors:

Poyil Pratheeshkumar

University of Kentucky

Manu Kanjoormana Aryan

Amala Cancer Research Centre Amala Institute of Medical Sciences

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The guest editorial team would like to thank all external reviewers for their expert assistance and all authors who submitted their work to the issue.

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Editorial

Phytochemicals in Cancer Prevention and Therapy

Poyil Pratheeshkumar,1Young-Ok Son,2Preethi Korangath,3

Kanjoormana Aryan Manu,4and Kodappully Sivaraman Siveen5

1Department of Toxicology and Cancer Biology, College of Medicine, University of Kentucky, Lexington, KY 40536, USA

2Cell Dynamics Research Center and School of Life Sciences, Gwangju Institute of Science and Technology (GIST),

Gwangju 61005, Republic of Korea

3Breast Cancer Program, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA

4Division of Cancer and Stem Cell Biology, DUKE-NUS Graduate Medical School, Singapore 169857

5Translational Research Institute, Academic Health System, Hamad Medical Corporation, P.O. Box 3050, Doha, Qatar

Correspondence should be addressed to Poyil Pratheeshkumar; pratheeshkumar.poyil@uky.edu

Received 25 October 2015; Accepted 25 October 2015

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly

cited.

Despite advances in modern medicine, cancer is still the

major cause of mortality in both developing and developed

countries. Search for safer and more eective chemopreven-

tion and treatment strategy is a need for the improvement

of patient care in the eld. Prevention may be more eective

and less costly because cancer is largely a preventable disease

which could be attributed to a greater extent to lifestyle.

Dietaryphytochemicalshavebeenusedforthetreatmentof

cancer throughout history due to their safety, low toxicity, and

general availability. Population based studies suggest that a

reduced risk of cancer is associated with high consumption

of vegetables and fruits. Promising phytochemicals not only

disrupt aberrant signaling pathways leading to cancer but

also synergize with chemotherapy and radiotherapy. us,

the cancer chemoprevention and therapeutic potential of

naturally occurring phytochemicals are of great interest. In

this special issue we have collected many interesting original

research articles and reviews that provide solid evidence to

support the application of phytochemicals or dietary agents

in prevention and treatment of cancer.

is special issue contains 3 review articles and 9 original

peer-reviewed papers. A. M. Harrison et al. performed a

systematic review of the biomedical literature for the use of

phytochemicals for management of cancer therapy pain in

human subjects; X.-Y. Chen et al. explored the molecular

mechanisms underlying the antimetastatic activity of black

rice anthocyanins and identied its molecular targets in

HER2+breastcancercells;thestudybyY.Zengetal.

reports that Southwest China (especially Yunnan and Tibet)

is the center of lowest mortality of cancers in China based

on coevolution between human’s anticancer activities and

functional foods from crop origin center; M. Sugata et al.

studied the anti-inammatory and anticancer activities of

Taiwanese purple-eshed sweet potatoes (Ipomoea batatas L.

Lam.) extracts; R. Moo-Puc et al. investigated the antipro-

liferative activity of bonediol, an alkyl catechol isolated

from the Mayan medicinal plant Bonellia macrocarpa against

human prostate tumor cells; B. Moyo and S. Mukanganyama

demonstrate the antiproliferative potential of T. welwit s c h ii

extract on Jurkat T cells; C.-J. Tai et al. report the potential

of ethanolic extract of Taiwanofungus camphoratus (Antrodia

camphorata) to enhance the cytotoxicity of cisplatin and dox-

orubicin on human hepatocellular carcinoma cells; G. Wang

et al. explored the molecular mechanism of total avonoids

extracted from Cotinus coggygria against glioblastoma cancer

invitroandinvivo;M.N.Mallicketal.studiedtheanticancer

activity of hydroalcoholic extract of Picrorhiza kurroa and its

fractions; M. F. Abu Bakar et al. demonstrate that the Garcinia

dulcis fruit extract induced cytotoxicity and apoptosis in

HepG2 liver cancer cells; G. Weng et al. reported the cur-

cumin enhanced busulfan-induced apoptosis in leukemia

stem-like KG1a cells via downregulating the expression of

Hindawi Publishing Corporation

BioMed Research International

Volume 2015, Article ID 324021, 2 pages

http://dx.doi.org/10.1155/2015/324021

2BioMed Research International

survivin; S. Kumar and J. Kim in their review discuss

potency and selectivity of PLK-1-targeted inhibitors and their

molecular interactions with PLK-1 domains.

In conclusion, this special issue discussed the potential

anticancer phytochemicals and dietary agents, their molec-

ular targets, and their mechanisms of actions. e under-

standing of molecular mechanism of a specic plant derived

compound against a particular type of cancer will lead to

the invention of novel drug and drug targets for therapeutic

intervention.

Acknowledgments

e guest editorial team would like to thank all external

reviewers for their expert assistance and all authors who

submitted their work to the issue.

Poyil Pratheeshkumar

Young-Ok Son

Preethi Korangath

Kanjoormana Aryan Manu

Kodappully Sivaraman Siveen

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Virtual screaning of anticancer efficacy of phloretin against apoptotic targets – An In Silico molecular docking study

Article

Full-text available

Nov 2021

Recent advances demonstrate phytochemicals to be a potent anticancer therapeutic agent as various anti-cancer targets. This study depicts the anti-cancer potential against certain crucial common cancer targets leading to cancer cell proliferation and survival. The main objective of this study is to study the anti-cancer potential of phloretin against certain cancer targets. Ligand analysis was performed and Phloretin was chosen as the experimental ligand and Bcl-2, NF Kappa B, Carbonic anhydrase I (CA-1), Inducible Nitric Oxide Synthase (iNOS), Endothelial Nitric oxide synthase (eNOS), Caspase 3, and Caspase 9 proteins were chosen as targets. Induced fit molecular docking was performed by the use of Glide 6.5 software (Schrodinger - 2015). The docked poses were further evaluated based on binding energy, Conformational changes, and the amino acid residues involved in the protein-ligand interaction. The docking results depicted that phloretin showed notable binding affinity especially with carbonic anhydrase I, ENOS, and INOS. It also showcased significant potential against Caspase 3 and NF Kappa, thereby showing its potential as an effective anti-cancer therapeutics. During this study, the Inhibitory potential of Phloretin was studied as a result of this molecular docking study. This Insilico study revealed the binding efficiency of phloretin against the aforementioned targets. In vitro analysis is required for further validation of this data.

Unraveling the antimicrobial efficacy and chemical fingerprinting of medicinal plants against the WHO’s prioritized pathogens

Article

Full-text available

Jan 2024

Background The global spread of drug-resistant organisms has necessitated the search for alternative treatments against bacterial and candidal resistant pathogens. Plants have long been used as traditional medicines to ameliorate various diseases, and their antimicrobial properties are still being explored. The aim of the present study is to assess the antimicrobial activity of extracts from Alstonia scholaris , Orthosiphon aristatus , Sphaeranthus amaranthoides , Crateva magna and Garcinia travancorica against bacteria and Candida pathogens. Results Out of 60 different sequential extracts tested, several showed moderate to good antimicrobial activity. Among them, ethyl acetate extract of G. travancorica exhibited significant activity against Lactobacillus acidophilus (17 mm) followed by Staphylococcus aureus (16 mm), Escherichia coli (13 mm), Proteus mirabilis (12 mm), Staphylococcus epidermis, Candida krusei (11 mm), Candida glabrata (10 mm) and the chloroform extract from O. aristatus showed good activity against S. epidermis, L. acidophilus (13 mm), S. aureus, Escherichia fergusonii , C. krusei (12 mm), C. glabrata, E. coli (11 mm) and Klebsiella pneumoniae (10 mm), respectively. In addition, GC–MS analysis revealed the presence of nine major compounds in G. travancorica and ten compounds in O. aristatus which were responsible for the significant antimicrobial activity. Conclusions These findings highlight the potential of G. travancorica and O. aristatus as sources for developing new antimicrobial agents against the World Health Organization’s (WHO) prioritized pathogens. Further research on these plants could lead to the discovery and synthesis of novel therapeutic agents with enhanced antimicrobial properties. Graphical abstract

Identification of Therapeutic Leads from Ficus hispida Fruit Phytochemicals against Prostate Cancer Using Pharmacoinformatic and Molecular Dynamics Simulation Approach

Preprint

Full-text available

Jun 2023

Prostate cancer is one of the leading causes of death and the most common cancer type in men. In this study, potential leads from the phytochemicals of Ficus hispida fruit were screened using in silico tools against androgen receptor (AR), a known target for prostate cancer. PASS online and ADMET tools were used to screen specific phytochemicals that are relevant to prostate cancer treatment and have drug-like properties. Of 13, a total of 10 phytochemicals passed PASS online and ADMET screening. Next, a total of three phytochemicals, including nodakenetin (CID: 26305), isowigtheone hydrate (CID: 66728267), and 7-hydroxycoumarin (CID: 5281426) were selected based on their docking scores (-9.946 to -7.653 kcal/mol) and relevance to selective bioactivity. The MD simulation further confirmed the binding stability of these three phytochemicals with their target AR protein and determined that the main amino acid residues mainly responsible for this stability including RMSD, RMSF, and post simulation binding free energies. These findings suggest that these three phytochemicals of Ficus hispida fruit can further be developed as prospective therapeutics against prostate cancer.

In vitro cytotoxic and antiproliferative activity of an aqueous extract from Phyllanthus comosus

Article

Full-text available

Dec 2021
Rev Cubana Med Trop

Introducción: Desde los inicios de la medicina antigua, las plantas han sido utilizadas como tratamiento en diversas enfermedades incluyendo las de naturaleza infecto-contagiosa y el cáncer. Son numerosos los informes sobre las propiedades biológicas del género Phyllanthus. Objetivo: Evaluar la actividad citotóxica y antiproliferativa de un extracto acuoso de Phyllanthus comosus en tres líneas celulares, dos de origen tumoral (SiHa y HeLa) y una no tumoral (Vero). Métodos: La actividad citotóxica se evaluó mediante el método del MTT y la capacidad antiproliferativa mediante el ensayo de detección de inhibición de colonias o clonogénico. Se tuvieron en cuenta valores como la concentración citotóxica media (CC50), índice selectivo y porcentaje de disminución de la proliferación celular. Resultados: En el ensayo de citotoxicidad se obtuvieron CC50 similares para ambas líneas tumorales; mientras que el valor para la línea Vero resultó tres veces menos tóxico, con valores de índice de selectividad mayor que tres. El ensayo clonogénico demostró inhibición de la proliferación en las líneas tumorales, mientras que en células Vero no se observó inhibición de la capacidad de formación de colonias. Conclusiones: El extracto de P. comosus es más citotóxico para las líneas tumorales SiHa y HeLa que para las células Vero, no tumorales. Además, la inhibición de la formación de clonos celulares en ambas líneas tumorales evidencia su acción antiproliferativa y selectiva, lo que argumenta su potencialidad antitumoral in vitro

PHARMACEUTICAL SCIENCES SJIF Impact Factor: 7.187 IN SILICO SCREENING OF POTENTIAL DRUG (PHYTOCHEMICALS) AGAINST INTERLEUKIN-6 THE KEY PROTEIN INVOLVED IN METASTASIS

Article

Full-text available

Oct 2022

Cancer is not a single disease. It's a group of diseases characterized by the uncontrolled growth of cells which results in tumors. The cells from the tumor at one point will start spreading to other organs which are termed metastasis. Mostly 90 percent of cancer patients die due to metastasis. A lot of treatments fail because of the complexity of cancer. The cancer cells can keep on mutating to adapt to the new environment. There are many different treatments available for cancer. But the most common ones are radiotherapy and chemotherapy. Both treatments can kill the cancer cells most often they end up killing the normal cells too. Then reduced sensitivity of the cancer cells to these treatments particularly in the advanced stages of cancer leads to ineffective treatment. The release of secretory factors from the cancer cells confers resistance to the cancer cells against therapy. Interleukin 6 which is found to be high in the tumor microenvironment regulates different signaling pathways and confers resistance to the cancer cells against damage. There are a lot of natural phytochemicals which can block interleukin 6 and thereby block metastasis. In this study, we selected 80 phytochemicals and studied their interaction capacity with the Interleukin-6. The phytochemicals were analyzed using molecular docking studies ADME-properties, and drug-likeness using the Schrodinger software. The phytochemicals were then analyzed using different software like protox and toxpro to study the anticarcinogenic, immunogenic, and genotoxic effects as well as the toxicity effects. The phytochemical Secoisolariciresinol has significantly interacted with active residues and it is an Interleukin-6 antagonist according to the protox II app too, which supports our results.

Regulation of micro-RNA, epigenetic factor by natural products for the treatment of cancers: Mechanistic insight and translational Association

Article

Full-text available

Mar 2022

From onset to progression, cancer is a ailment that might take years to grow. All common epithelial malignancies, have a long latency period, frequently 20 years or more, different gene may contain uncountable mutations if they are clinically detectable. MicroRNAs (miRNAs) are around 22nt non-coding RNAs that control gene expression sequence-specifically through translational inhibition or messenger degradation of RNA (mRNA). Epigenetic processes of miRNA control genetic variants through genomic DNA methylation, post-translation histone modification, rework of the chromatin, and microRNAs. The field of miRNAs has opened a new era in understanding small non-coding RNAs since discovering their fundamental mechanisms of action. MiRNAs have been found in viruses, plants, and animals through molecular cloning and bioinformatics approaches. Phytochemicals can invert the epigenetic aberrations, a leading cause of the cancers of various organs, and act as an inhibitor of these changes. The advantage of phytochemicals is that they only function on cells that cause cancer without affecting normal cells. Phytochemicals appear to play a significant character in modulating miRNA expression, which is linked to variations in oncogenes, tumor suppressors, and cancer-derived protein production, according to several studies. In addition to standard anti-oxidant or anti-inflammatory properties, the initial epigenetic changes associated with cancer prevention may be modulated by many polyphenols. In correlation with miRNA and epigenetic factors to treat cancer some of the phytochemicals, including polyphenols, curcumin, resveratrol, indole-3-carbinol are studied in this article

Evaluation of phytoconstituents from selected medicinal plants and its synergistic antimicrobial activity

Article

Sep 2021
CHEMOSPHERE

Phytoconstituents of plants had enormous therapeutic potential against the wounds on skin. Plants like Tecoma stans, Manilkara zapota and Cassia fistula were some which had the ability to heal the wounds. However, there was limited research in Cassia fistula flowers and its synergism with plants on wound healing and its mechanism. Qualitative analysis was performed to confirm the presence of phytoconstituents like flavonoids, saponins and tannins in solvents:aqueous ethanol and methanol. All three components showed their attributes towards wound healing. Results of antimicrobial activity clearly stated that, methanol extract of the Cassia fistula flowers at increasing concentration, showed the maximum zone of inhibition of 27 mm at 100 μl (antibacterial assay) and 18 mm at 100 μl (anti-fungal assay). They had higher potential against the selective microbes Staphylococcus aureus and Aspergillus niger. The combination of C. fistula flowers and C. fistula leaves; C. fistula flowers and M. zapota leaves showed maximum zone of inhibition of 23 mm and 21 mm for anti-bacterial; 22 mm and 23 mm for antifungal at 100 μl respectively. The C. fistula flowers along with the Manilkara zapota leaves and C. fistula leaves enhanced the antimicrobial nature than the individual plants. The antimicrobial properties present in the plants would engage them in future for developing an improved medicine for wound healing. Thus a polyherbal plant solution containing equal proportions of plants, tested for the antibacterial activity, succeeded by showing its higher inhibition of 25 mm at 100 μl.This concluded that the synergism of plants had higher efficiency in microbial activity than the individual samples hence proving the plants attributes towards the wound healing.

Controlling non small cell lung cancer progression by blocking focal adhesion kinase-c-Src active site with Rosmarinus officinalis L. phytocomponents: An in silico and in vitro study

Article

Full-text available

Jan 2021
J Canc Res Therapeut

Background: Non small cell lung cancer (NSCLC) is a global, fatal oncological malady to which conventional and targeted therapies proved less effective with consequent side effects; hence, phytocomponents from herbal sources may provide potent alternative and should be tested for cancer intervention. Activation and overexpression of proto‑oncogene tyrosine kinase Src (c‑Src) and focal adhesion kinase (FAK) lead to cell proliferation and invasion. Hence, in the present investigation, in silico analysis was carried out to identify molecular intervention of phytocomponents in blocking the active site and thus inhibiting c‑Src and FAK activation, which in turn could control progression of NSCLC. Materials and Methods: In silico analysis was carried out using Molegro Virtual Docker, Molegro Molecular Viewer, and ClusPro server for ligand–protein and protein–protein interaction study. Phytochemical analysis and assay for antioxidant activity of hydroalcoholic extract of Rosmarinus officinalis L. were carried out using standard phytochemical tests, high‑performance thin‑layer chromatography, and 2, 2‑diphenyl‑1‑picrylhydrazyl assay. Effectiveness of extract in arresting cell proliferation was confirmed using 3‑(4, 5‑dimethylthiazol‑2‑yl)‑2, 5‑diphenyltetrazolium bromide (MTT) assay on A549 cell line. Results: In silico analysis indicated effective binding of rosmarinic acid to the active site of target proteins FAK and c‑Src, blocking their activity. MTT assay revealed potent antiproliferative activity of hydroalcoholic extract which acted in dose‑dependent manner. Phytochemical analysis confirmed that the extract was rich in phytocomponents and had antioxidant activity of 94.9%, which could therefore effectively eliminate free radicals and inhibit cell progression. Conclusion: In silico and in vitro studies confirmed that phytocomponents present in hydroalcoholic extract of R. officinalis L. could effectively block the active site of target proteins and thus controlled cell proliferation on NSCLC cells, suggesting herb as an effective alternative medicine for the treatment of NSCLC.

The Elusive Road Towards Effective Cancer Prevention and Treatment

Book

Oct 2022

Cancer will remain a global major health problem unless new diagnostic, prognostic, and management approaches are discovered to address both loss of life and quality of life. Here we summarize the general physiology, pathology, heterogeneity, and evolution of cancer, current status, limitations and challenges associated with prevention, incidence, treatment, survival, and mortality, as well as future directions with regards to solid tumors. Perspectives are provided on how to improve pre-clinical understandings, outcomes, and patient care. Further, this comprehensive, timely overview of the literature has educational value as part of an academic course, seminar, or as a supplementary text.

Proceedings, 2020, la ValSe-Food 2019

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