Abstract:
BACKGROUND:Hepatocellular Carcinoma (HCC), the second leading cause of cancer-related mortality with over half a million new cases diagnosed annually in the world, accounts for nearly 70% of cancer deaths in parts of Asia and Africa. Podophyllum, one of the important members of the lignane class of natural products derived from plants in Podophyllum peltatum L., has been shown to suppress tumor growth in various cancers. However, the effects of Podophyllum compounds on HCC and the mechanisms for its tumor-suppressive function remain unknown. METHODS:A molecular docking study was employed to the analysis of the interaction between compounds and their targeted proteins. Cell proliferation was measured by MTT assay. Western blot analysis was used to evaluate protein expression. qRT-PCR was performed to assess RNA expression. RESULTS:Molecular docking analysis was consistent with the beneficial effect of fluorine atom substituent in the 3-position of 2-aminopyridine in our previous study. Also, P-3F and D-3F displayed the most potent cytotoxicities against PLC/PRF/5 with p53-R249S and weakest inhibition of L02 (normal liver cell) growth. However, these derivatives had no effect on the suppression of HepG2 (wild-type p53) and Hep3B (p53-null) proliferation significantly. Further study showed that both compounds increase γ-H2AX expression in PLC/PRF/5 cell, along with repression of the c-Myc activation, purportedly by induction of p53 level and transcriptional activation. CONCLUSION:The results suggested that podophyllum derivatives containing fluorine atom in the 3-position of 2- aminopyridine could inhibit the growth of HCC harboring p53-R249S by restoring the activity of p53 with decreasing the level of c-Myc.
journal_name
Anticancer Agents Med Chemjournal_title
Anti-cancer agents in medicinal chemistryauthors
Chen H,Zhang M,Wang Z,Li L,Li Q,Wang Hdoi
10.2174/1871520620666200218110047subject
Has Abstractpub_date
2020-01-01 00:00:00pages
865-874issue
7eissn
1871-5206issn
1875-5992pii
ACAMC-EPUB-104599journal_volume
20pub_type
杂志文章abstract:BACKGROUND:Chronic myeloid leukemia (CML), also recognized as chronic myelogenous leukemia, is initiated in some types of blood-forming cells of the bone marrow. The therapeutic approach to CML is usually chemotherapy; however, severe side effects and complications are major problems in the clinical research. Thus, rec...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/1871520616666160404112945
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abstract::Angiogenesis inhibitors have a major role in the treatment of varying cancers today. While originally thought to be independent of resistance, increasing data suggests varying mechanisms that bring about drug resistance, either intrinsically or through adaptation. The role of vascular endothelial growth factor single ...
journal_title:Anti-cancer agents in medicinal chemistry
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abstract::Apoptosis, or programmed cell death, is an important physiologic process multicellular organisms use to maintain homeostasis by providing a means for elimination of redundant cells during development. Furthermore, cells that have become damaged or are defective undergo apoptosis to prevent disease. It is an important ...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
doi:10.2174/187152009789377763
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
doi:10.2174/18715206113139990314
更新日期:2013-12-01 00:00:00
abstract::Cilengitide, a cyclic RGD pentapeptide, is currently in clinical phase III for treatment of glioblastomas and in phase II for several other tumors. This drug is the first anti-angiogenic small molecule targeting the integrins αvβ3, αvβ5 and αvβ1. It was developed by us in the early 90s by a novel procedure, the spatia...
journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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doi:10.2174/1871520618666181029133041
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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doi:10.2174/1871520617666170918130126
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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abstract::Tea catechins exhibit a broad range of pharmacological activities that impart beneficial effects on human health. Epigallocatechin-3-gallate (EGCG), one of the major tea catechins, has been widely associated with cancer prevention and treatment. In addition, tea catechins in combination with anticancer drugs are being...
journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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更新日期:2008-08-01 00:00:00
abstract::Life expectancy has impressively increased over the past century and the US population over 65 years is rapidly growing, especially those over 80 years. In fact, persons older than 80 years have increased by more than 250% between the years 1960 and 2000, and it is expected that the population aged >75 years will trip...
journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章
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更新日期:2016-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2021-01-12 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
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更新日期:2018-01-01 00:00:00
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journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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abstract:BACKGROUND:The cause of cervical cancer can be traced to Human Papilloma Virus (HPV) along with other, nonviral factors. The uterine cervix is reactive to hormones, and female hormones have been implicated in cervical cancer pathogenesis. Previous studies have indicated that malignant cervical cells tend to lose Estrog...
journal_title:Anti-cancer agents in medicinal chemistry
pub_type: 杂志文章,评审
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