Seminars in Cancer Biology, 2016, 40-41:48-81.

Targeting arachidonic acid pathway by natural products for cancer prevention and therapy

Nagendra Sastry Yarla, Anupam Bishayee, Gautam Sethi, et al

Department of Biochemisty/Bionformatics, Institute of Science, GITAM University, Rushikonda, Visakhapatnam 530 045, Adhra Pradesh, India; et al

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.

英国《癌症生物学研讨会》, 2016, 40-41:48-81.

天然靶向产物花生四烯酸用于癌症预防和治疗的途径

生物化学/生物信息学，GITAM大学科学研究所，Rushikonda，Visakhapatnam 530 045，Adhra Pradesh，印度; et al

花生四烯酸（AA）的代谢途径在癌症发生中发挥关键作用。因此，AA途径代谢酶磷脂酶A2s（PLA2s），环氧化酶（COXs）和脂氧合酶（LOXs）及其代谢产物，如前列腺素和白三烯，被认为是新的预防和治疗癌症的靶点。具有生物活性的天然产物是新型的癌症预防和治疗药物，由于其安全性，已被广泛应用临床实践中。AA 的通路抑制作用已发展成预防某些癌症的化学预防和治疗药物。姜黄素，白藜芦醇，芹菜素，花色素类、 黄连素、 鞣花酸、 丁香酚、 漆黄素，果酸，[6]-姜酚、 guggulsteone、 番茄红素、 染料木黄酮是众所周知的针对多个通路，包括环氧合酶-2 的癌症化学预防药物。创木酸和黄芩素通过抑制 LOXs可以预防多种癌症的化学预防分子。已经鉴定了几个 PLA2s 抑制性自然产物具有针对各种癌症的化学预防和治疗潜力。在本综述中，我们批判性地讨论了天然产物作为针对各种肿瘤疾病，包括前列腺，胰腺，肺，皮肤，胃，口腔，血液，头颈部，结肠直肠，肝，子宫颈和乳腺癌，通过靶向AA通路。此外，审查评估AA途径抑制天然产物在癌症中的临床研究的当前状态。此外，还讨论了各种新出现的问题，包括生物利用度，毒性和组合治疗的可探测性，用于开发AA途径抑制性天然产物作为针对人类恶性肿瘤的化学预防和治疗药物。