Apoptosis-inducing activity of new pyrazole emodin derivatives in human hepatocellular carcinoma HepG2 cells
ABSTRACT A series of new pyrazole derivatives from emodin synthesized in our lab have been shown to have much stronger cytotoxicity than emodin against various tumor cell lines. This study was to examine the apoptosis-inducing activity of these new emodin derivatives in human hepatocellular carcinoma HepG2 cell culture for a better understanding of their cytotoxic effects on the cancer cells. Several major events in the induction of cell apoptosis, nuclear chromatin condensation, DNA fragmentation, caspase-3 activation and poly ADP-ribose polymerase (PARP) cleavage were detected in the cells after treatment with the compounds at various concentrations. Of the seven emodin derivatives tested at a dose of 10 microM and within a treatment period of 24 h, only compounds 1 and 3 effectively induced all these apoptotic events in the cancer cells. The apoptosis-inducing activity of the compounds showed a positive correlation to their cytotoxic activity, suggesting a close connection between the growth inhibition and apoptosis induction of the cancer cells by these pyrazole emodin derivatives.
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ABSTRACT: Cancer is considered as one of the leading cause of death worldwide, especially in the economically developed countries. Over 12.7 million cancer cases with the death tolls reaching up to 7.6 million were in 2008 throughout globe.The situation is no any different in a country like India where death toll per year reaches upto 5.8 lakhs out of the 8.5 lakhs diagnosed clinical cases. Conventional therapies based on surgery, radiation therapy, chemotherapy, hormone therapy, immunoadjuvant therapy, cryotherapy, apoptin therapy and nanoparticles (to facilitate better drug delivery) are widely used but are having side effects, resulting in fatal outcome. Under such circumstances, herbal therapy forms an integral part of the alternative approach as they are cheaper and are without having any toxic effect. More than 50% of all modern drugs in clinical use are herbal products, many of them having the ability to control cancer and importantly, over 60% of cancer patients use them. Plants are used against various types of tumors/cancers such as sarcoma, lymphoma, carcinoma and leukemia. Natural non-steroidal anti-inflammatory substances and their roles to prevent cancer need to be explored. Broadly, the anticancer mechanisms of herbs have been divided into two distinct categories viz. direct cytotoxicity and immunomodulation. Several herbs add to the versatility of cancer management by boosting up the immune system and thereby, preparing the body to defend against future or existing cancer and include Morinda citrifolia, Catharanthus roseus, Taxus brevifolia, Camptotheca acuminate, Podophyllum species, Tinospora cordofolia, Glycyrrhiza glabra etc. having promising anticancer properties. India is an abode of several botanical plants effective against tumours of brain and uterus; abdomen and glandular organs; throat and breast cancer. Thus, it is anticipated that plants can provide potential bioactive compounds for the development of new therapies to combat cancer. But their efficacy in humans and animals need to be evaluated. Thus, rigorous safety and quality evaluation, comparative clinical studies using modern techniques, proper standardization methods, and good manufacturing practices are extremely important. Isolation and purification of biologically active components from the bulk extracts need to be carried out side by side to understand the basic mechanisms of the drug action. All these form the topic of discussion of this review in order to find out solution to this grave disease of mankind and animals without causing much stress and side effects.
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ABSTRACT: Two anthraquinones which inhibit activity of the Src tyrosine kinase were isolated from a water extract of Hedyotis diffusa WILLD. and identified as 2-hydroxy-3-methylanthraquinone (compound 1) and 1-methoxy-2-hydroxyanthraquinone (compound 2). Both compounds showed inhibitory activity against protein tyrosine kinases v-src and pp60src and arrested the growth of SPC-1-A, Bcap37 and HepG2 cancer cells. Observation of mitochondrial membrane potential collapse and caspase-3 activation following treatment with the compounds indicates that their apoptotic induction activity may act via the mitochondrial apoptotic pathway. Compared with compound 2, compound 1 is more active as an antagonist of Src kinase, which might account for its higher potency to induce growth arrest and apoptosis. These results provide a deeper insight into the functions of these two simple anthraquinones and the anti-tumour pathway of Hedyotis diffusa WILLD.Biological & Pharmaceutical Bulletin 06/2008; 31(6):1075-8. DOI:10.1248/bpb.31.1075 · 1.78 Impact Factor
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ABSTRACT: Emodin (1,3,8-trihydroxy-6-methylanthaquinone), an active component present in the root and rhizome of Rheum palmatum L. (Polygonaceae) has anti-bacterial, anti-tumor, diuretic and vasorelaxant effects. However, its mechanism of action on the cell migration and invasion of human neuroblastoma cancer SH-SY5Y cells is not fully understood. In this study, firstly, the effects of emodin on the percentage of viable cells were examined by using MTT assay and it was found that emodin induced dose-and time-dependent inhibition in human neuroblastoma SH-SY5Y cells. Second, the effects of emodin on the migration and invasion of SH-SY5Y cells were examined by using wound assay and matrigel counting and the results showed that emodin suppressed the migration and invasion of SH-SY5Y cells. Third, we examined the effect of emodin on the levels of associated proteins by using Western blotting and the results indicated that emodin inhibited the levels of GRB2, RhoA, HIF-1alpha, VEGF, FAK, iNOS, COX2, p-p38, p-c-jun, MMP2, MMP9 and MMP7 but promoted the levels of PKC, PI3K, MEKK3 and NF-kappaB p65 that led to the inhibition of migration and invasion of SH-SY5Y cells in vitro.Neurochemical Research 04/2009; 34(9):1575-83. DOI:10.1007/s11064-009-9946-3 · 2.55 Impact Factor