Apoptosis-Inducing Activity of New Pyrazole Emodin Derivatives in Human Hepatocellular Carcinoma HepG2 Cells

School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, China.
Biological & Pharmaceutical Bulletin (Impact Factor: 1.83). 07/2007; 30(6):1113-6. DOI: 10.1248/bpb.30.1113
Source: PubMed


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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    • "In recent years, apoptosis has emerged as the major mechanism by which anticancer agents eliminate preneoplastic or neoplastic cells. It has been proven that emodin can induce apoptosis through increasing nuclear condensation and DNA fragmentation [18,19], activating caspase −9 and −3 [20], inducing cell-cycle arrest [12,21], elevating level of ROS [22,23], decreasing level of NF-κB [24,25], activating PI3K/AKT pathway [26] and PKC pathway [20,27], However, there is no available information to address how emodin affects human cervical cancer cells in vitro. The aim of the present study is to investigate the potential anticancer effects of emodin on human cervical cancer cells and the underlying molecular mechanisms. "
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    ABSTRACT: Emodin is a natural anthraquinone derivative isolated from the Rheum palmatum L. Aim: The aim of the present study was to investigate the effect of emodin on the apoptosis of the human cervical cancer line HeLa and to identify the mechanisms involved. Relative cell viability was assessed by MTT assay after treatment with emodin. Cell apoptosis was detected with TUNEL, Hoechst 33342 staining and quantified with flow cytometry using annexin FITC-PI staining. The percentage of apoptotic cells was 0.8, 8.2, 22.1, and 43.7%, respectively. The mRNA levels of Caspase-9, -8 and -3 detected by Real-time PCR after treatment with emodin were significantly increased. Emodin increased the protein levels of Cytochome c, Apaf-1, Fas, FasL, and FADD but decreased the protein levels of Pro-caspase-9, Pro-caspase-8 and Pro-caspase-3. We conclude that the emodin inhibited HeLa proliferation by inducing apoptosis through the intrinsic mitochondrial and extrinsic death receptor pathways.
    Full-text · Article · Jul 2013 · Cancer Cell International
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    • "Our results agree with the literature data regarding Vismia laurentii [16], Psorospermum febrifugum [25]–[27] and Ficus asperifolia [8] anticancer potential, and we additionally identify the Pentadesma butyracea extract as a good antiproliferative agent, after an earlier report on its antimalarial activity [11]. We identify here two new targets: ovary cancer and skin malignancies, in which the prodrug potential of the natural substances can be used as a new therapeutic approach. "
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    ABSTRACT: Traditional remedies have a long-standing history in Cameroon and continue to provide useful and applicable tools for treating ailments. Here, the anticancer, antimicrobial and antioxidant activities of ten antioxidant-rich Cameroonian medicinal plants and of some of their isolated compounds are evaluated.The plant extracts were prepared by maceration in organic solvents. Fractionation of plant extract was performed by column chromatography and the structures of isolated compounds (emodin, 3-geranyloxyemodin, 2-geranylemodin) were confirmed spectroscopically. The antioxidant activity (AOA) was determined using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) bleaching method, the trolox equivalent antioxidant capacity (TEAC), and the hemoglobin ascorbate peroxidase activity inhibition (HAPX) assays. The anticancer activity was evaluated against A431 squamous epidermal carcinoma, WM35 melanoma, A2780 ovary carcinoma and cisplatin-resistant A2780cis cells, using a direct colorimetric assay. The total phenolic content in the extracts was determined spectrophotometrically by the Folin-Ciocalteu method. Rumex abyssinicus showed the best AOA among the three assays employed. The AOA of emodin was significantly higher than that of 3-geranyloxyemodin and 2-geranylemodin for both TEAC and HAPX methods. The lowest IC(50) values (i.e., highest cytotoxicity) were found for the extracts of Vismia laurentii, Psorospermum febrifugum, Pentadesma butyracea and Ficus asperifolia. The Ficus asperifolia and Psorospermum febrifugum extracts are selective against A2780cis ovary cells, a cell line which is resistant to the standard anticancer drug cisplatin. Emodin is more toxic compared to the whole extract, 3-geranyloxyemodin and 2-geranylemodin. Its selectivity against the platinum-resistant A2780cis cell line is highest. All of the extracts display antimicrobial activity, in some cases comparable to that of gentamycin.
    Full-text · Article · Feb 2013 · PLoS ONE
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    • "Biliary and urinary tract cancer Amir et al., 2003 ; Naik and Juvekar, 2003 37. Podophyllum peltatum, Podophyllum emodi Podophyllum hexandrum Berberidaceae Podophyllotoxin, Etoposide and Teniposide Lymphomas, bronchial, lung and testicular cancers Cragg et al., 1994; Giri and Narasu, 2000; Rahal et al., 2009 38. Psorospermum febrifugum Clusiaceae Psorospermin, Emodin, Leukemia, Hepatic and colon carcinoma, ovary, prostate, lung cancer Kupcha et al., 1980; Wang et al., 2007; Li et al., 2009; Su et al., 2010; Ok et al., 2012; Suboj et al., 2012 39. "
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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.
    Full-text · Article · Jan 2013
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