title: Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.
abstract: Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A2s (PLA2s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA2s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed.
authors: Department of Biochemisty/Bionformatics, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Adhra Pradesh, India.
authors: Nagendra Sastry
authors: NS
authors: Yarla
authors: Department of Pharmaceutical Sciences, College of Pharmacy, Larkin Health Sciences Institute, 18301 N. Miami Avenue, Miami, FL 33169, USA. Electronic address: abishayee@ULarkin.org.
authors: Anupam
authors: A
authors: Bishayee
authors: Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600, Singapore; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Biosciences Research Precinct, Curtin University, Western Australia 6009, Australia.
authors: Gautam
authors: G
authors: Sethi
authors: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500 046, Telagana, India.
authors: Pallu
authors: P
authors: Reddanna
authors: Department of Animal Biology, School of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad 500 046, Telagana, India; Department of Environmental Health Sciences, Laboratory of Human Environmental Epigenomes, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, USA.
authors: Arunasree M
authors: AM
authors: Kalle
authors: Toxinology/Toxicology and Drug Discovery Unit, Center for Emerging Technologies, Jain Global Campus, Jain University, Kanakapura Taluk, Ramanagara 562 112, Karnataka, India.
authors: Bhadrapura Lakkappa
authors: BL
authors: Dhananjaya
authors: Department of Biochemisty/Bionformatics, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Adhra Pradesh, India; Department of Microbiology and Bioinformatics, Bilaspur University, Bilaspur 495 001, Chhattisgarh, India.
authors: Kaladhar S V G K
authors: KS
authors: Dowluru
authors: Department of Environmental Sciences, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Adhra Pradesh, India.
authors: Ramakrishna
authors: R
authors: Chintala
authors: Department of Biochemisty/Bionformatics, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Adhra Pradesh, India. Electronic address: drdgraoresearchgroup@gmail.com.
authors: Govinda Rao
authors: GR
authors: Duddukuri
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D016718:Arachidonic Acid / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000188:drug therapy / Q000517:prevention & control*; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D016718:Arachidonic Acid
keywords: Arachidonic acid pathway; Bioactive natural products; Cancer; Prevention; Therapy