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Wednesday, November 2, 2016
Highlighted Article: Molecular Mechanisms of Anti-cancer Activities of β-elemene: Targeting Hallmarks of Cancer
Molecular Mechanisms of Anti-cancer Activities of β-elemene: Targeting Hallmarks of Cancer
Author(s):
Shiyu Jiang, Chunhua Ling, Wei Li, Hongxin Jiang, Qiaoming Zhi and Min Jiang Pages 1426 - 1434 (9)
Abstract:
Increasing knowledge on the hallmark characteristics of cancer and tumor pharmacology has promoted the introduction of phytochemicals, such as traditional Chinese medicine (TCM) in cancer therapy, which modulate numerous molecular targets and exert anticancer activities. β-elemene, an active and non-toxic compound isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been explored as a potent anti-cancer agent against multiple cancers in extensive clinical trials and experimental research in vivo and in vitro. β-elemene exerts therapeutic potential via modulation of core hallmark capabilities of cancer by suppressing proliferative signaling, such as MAPK and PI3K/Akt/mTOR pathway, inducing cell death, up-regulating growth suppressors, deactivating invasion and metastasis and interacting replicative immortality and attenuating angiogenesis. Recent studies have significantly improved our understanding of anti-cancer activities and underlying molecular mechanisms of this Chinese medicine. This review presents these novel findings regarding the unique properties of β-elemene as an agent for cancer treatment, with an emphasis on multi-targeting biological and molecular regulation.
Keywords:
β-elemene; anti-cancer activity; hallmarks of cancer; drug resistance.
Affiliation:
Department of General Surgery, The First Affiliated Hospital of Soochow University, No. 188, Shi Zi Road, Suzhou 215006, China., Department of Oncology, The First Affiliated Hospital of Soochow University, No. 188, Shi Zi Road, Suzhou 215006, China.
Graphical Abstract:
For More Information Please Visit Our Website Anti Cancer Agents in Medicinal Chemistry
Tuesday, October 25, 2016
Most Cited Article: Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways
Cytochromes P450 and
Skin Cancer: Role of Local Endocrine Pathways
Author(s):
Skin is the largest body organ forming a
metabolically active barrier between external and internal environments. The
metabolic barrier is composed of cytochromes P450 (CYPs) that regulate its
homeostasis through activation or inactivation of biologically relevant
molecules. In this review we focus our attention on local steroidogenic and
secosteroidogenic systems in relation to skin cancer, e.g., prevention,
attenuation of tumor progression and therapy. The local steroidogenic system is
composed of locally expressed CYPs involved in local production of androgens,
estrogens, gluco- and mineralo-corticosteroids from cholesterol (initiated by
CYP11A1) or from steroid precursors delivered to the skin, and of their
metabolism and/or inactivation. Cutaneous 7-hydroxylases (CYP7A1, CYP7B1 and
CYP39) potentially can produce 7-hydroxy/oxy-steroids/sterols with modifying
effects on local tumorigenesis. CYP11A1 also transforms 7-dehydrocholesterol
(7DHC)→22(OH)7DHC→20,22(OH)2-7DHC→7-dehydropregnenolone, which can be further
metabolized to other 5,7- steroidal dienes. These 5,7-dienal intermediates are
converted by ultraviolet radiation B (UVB) into secosteroids which show
pro-differentiation and anti-cancer properties. Finally, the skin is the site
of activation of vitamin D3 through two alternative pathways. The classical one
involves sequential hydroxylation at positions 25 and 1 to produce active
1,25(OH)2D3, which is further inactivated through hydroxylation at C24. The
novel pathway is initiated by CYP11A1 with predominant production of 20(OH)D3
which is further metabolized to biologically active but non-calcemic
D3-hydroxyderivatives. Classical and non-classical (novel) vitamin D analogs
show pro-differentiation, anti-proliferative and anticancer properties. In
addition, melatonin is metabolized by local CYPs. In conclusion cutaneously
expressed CYPs have significant effects on skin physiology and pathology trough
regulation of its chemical milieu.
For More Information Please Visit Our Website Anticancer Agent in Medicinal Chemistry
Skin is the largest body organ forming a metabolically active barrier between external and internal environments. The metabolic barrier is composed of cytochromes P450 (CYPs) that regulate its homeostasis through activation or inactivation of biologically relevant molecules. In this review we focus our attention on local steroidogenic and secosteroidogenic systems in relation to skin cancer, e.g., prevention, attenuation of tumor progression and therapy. The local steroidogenic system is composed of locally expressed CYPs involved in local production of androgens, estrogens, gluco- and mineralo-corticosteroids from cholesterol (initiated by CYP11A1) or from steroid precursors delivered to the skin, and of their metabolism and/or inactivation. Cutaneous 7-hydroxylases (CYP7A1, CYP7B1 and CYP39) potentially can produce 7-hydroxy/oxy-steroids/sterols with modifying effects on local tumorigenesis. CYP11A1 also transforms 7-dehydrocholesterol (7DHC)→22(OH)7DHC→20,22(OH)2-7DHC→7-dehydropregnenolone, which can be further metabolized to other 5,7- steroidal dienes. These 5,7-dienal intermediates are converted by ultraviolet radiation B (UVB) into secosteroids which show pro-differentiation and anti-cancer properties. Finally, the skin is the site of activation of vitamin D3 through two alternative pathways. The classical one involves sequential hydroxylation at positions 25 and 1 to produce active 1,25(OH)2D3, which is further inactivated through hydroxylation at C24. The novel pathway is initiated by CYP11A1 with predominant production of 20(OH)D3 which is further metabolized to biologically active but non-calcemic D3-hydroxyderivatives. Classical and non-classical (novel) vitamin D analogs show pro-differentiation, anti-proliferative and anticancer properties. In addition, melatonin is metabolized by local CYPs. In conclusion cutaneously expressed CYPs have significant effects on skin physiology and pathology trough regulation of its chemical milieu.
