Dendrosomal curcumin increases expression of the long non-coding RNA gene MEG3 via up-regulation of epi-miRs in hepatocellular cancer
Abstract Background: Hepatocellular carcinoma is the fifth most common cancer worldwide, with poor prognosis and resistance to chemotherapy. This gives novel cancer treatment methods an overwhelming significance. Epigenetic therapy of cancer is useful in reversing some of the cancer defects because of reversibility of the epigenetic alterations. Non-protein coding transcripts are the major part of our transcriptome. MEC3 is a tumor suppressor long non-coding RNA being expressed in many normal tissues. Methylation of MEG3 promoter region elicits the decrease in its expression in hepatocellular cancer cells. Bioactive nutrients including curcumin offer great potential in altering DNA methylation status which is catalyzed via DNMT1, DNMT3A and 3B.
Purpose: Herein, we aimed to study RNA-based epigenetic effects of dendrosomal curcumin (DNC) on hepatocellular cancer (HCC).
Study design: To this end miRNA-dependent regulation of MEG3 expression under treatment with DNC was studied by evaluating the modulatory involvement of miR-29a for DNMT3A and 3B and miR-185 for DNMT1. Methods: We evaluated DNC entrance to HCC cells with the use of fluorescent characteristics of curcumin. Next we performed the MTT assay to evaluate DNC and dendrosome effects on HCC cell viability. The coding and non-coding genes expression analyses were done using quantitative-PCR.
Results: In result we found that the DNC dependent overexpression of miR-29a and miR-185 (P < 0.01) can down-regulate the expression of DNMT1, 3A and 3B (P < 0.05) and subsequently overexpresses MEG3 (P < 0.05)
Conclusion: DNC potentially can induce DNA hypomethylation and reexpression of silenced tumor suppressor genes in HCC. These data suggest that DNC could be an effective choice for epigenetic therapy of HCC
Source : Phytomedicine: International Journal of Phytotherapy + Phytopharmacology Link to Full Article.
1Faculty of Pharmacy, Chiang Mai University, Chiang Mai 50200, Thailand 2Manose Health and Beauty Research Center, Chiang Mai 50200, Thailand 3Department of Biotechnology and Material Chemistry, Nihon University Junior College, Chiba 274-8501, Japan 4College of Science and Technology, Nihon University, Tokyo 101-8308, Japan 5Akihisa Medical Clinic, 1086-3 Kamo, Sanda-shi, Hyogo 669-1331, Japan 6Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
Abstract Thai/Lanna medicinal plant recipes have been used for the treatment of several diseases including liver cancer. In this study, methanolic extracts (MEs) of 23 plants were tested for antiproliferative activity on human hepatoma cell line (Hep G2) by the sulforhodamine B (SRB) assay. Nine MEs with potent antiproliferative activity (IC50 < 100 µg/mL) were obtained and further semipurified by liquid/liquid partition extraction. The semipurified fractions were tested for the antiproliferative and antioxidative activities. ME of Stemona collinsae and the semipurified extract and methanol-water fraction (MF) of Gloriosa superba gave the highest antiproliferative activity on HepG2 which were 4.79- and 50.07-fold cisplatin, respectively. The semipurified fractions showed an increased antiproliferative activity. MF of Caesalpinia sappan and HF of Senna alatashowed the highest free radical scavenging and metal chelating activities, respectively. The compound in n-hexane fraction (HF) of Ventilago denticulata which showed an increase in antiproliferative activity comparing to its ME was isolated and identified as emodin. This study has demonstrated the potential of the ME from S. collinsae, MF from G. superba, and emodin isolated from V. denticulata, for further development as an antiliver cancer agent.
1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China 2Department of Traditional Chinese Medicine, Henan Province People’s Hospital, Zhengzhou 221000, China
Pterocephalus hookeri is a widely applied Tibetan medicinal prescription for treatment of diseases such as flu, rheumatoid arthritis, and enteritis in China. It has been reported that Pterocephalus hookeri has anti-inflammatory and analgesic actions. However, the antitumor activity of Pterocephalus hookeri remains unknown. In the present study, we demonstrate that n-butanol extracts of Pterocephalus hookeri (YSC-ZDC) has a strong antitumor activity against hepatoma carcinoma cell in vitro and in vivo. YSC-ZDC inhibited proliferation of all cancer cell lines and significantly inhibited Hep3B cells proliferation in a dose- and time-dependant manner. Transmission electron microscopy, hoechst 33258 staining, and flow cytometry analysis revealed that YSC-ZDC induced apoptosis in Hep3B cells. YSC-ZDC treatment dramatically inhibited PDK1 and Akt phosphorylation in Hep3B cells. Moreover, YSC-ZDC increased Bax expression and inhibited Bcl-2 expression. In addition, YSC-ZDC inhibited growth hepatoma xenografts in vivo with no effect on body weight and spleen index. Consistent with results in vitro, YSC-ZDC increased Bax expression and inhibited Bcl-2 expression in tumor tissue. Taken together, this study shows YSC-ZDC with an antitumor activity bothin vitro and in vivo. Its mechanism underlying is related to blocking of the Akt pathway and regulation of Bcl-2 family proteins expression.
Antitumor Effect of Periplocin in TRAIL-Resistant Human Hepatocellular Carcinoma Cells through Downregulation of IAPs Chieh-Fang Cheng, I-Huang Lu, Hsiang-Wen Tseng, Chung-Yuan Sun, Li-Tsen Lin, Zong-Keng Kuo, I-Horng Pan, and Ching-Huai Ko
Biomedical Technology and Device Research Laboratories, Industrial Technology Research Institute, Hsinchu, Taiwan
Abstract Cortex periplocae is the dried root bark of Periploca sepium Bge., a traditional Chinese herb medicine. It contains high amounts of cardiac glycosides. Several cardiac glycosides have been reported to inhibit tumor growth or induce tumor cell apoptosis. We extracted and purified cortex periplocae and identified periplocin as the active ingredient that inhibited the growth of TNF-related apoptosis-inducing ligand-(TRAIL-) resistant hepatocellular carcinoma cells. The antitumor activity of periplocin was further increased by TRAIL cotreatment. Periplocin sensitized TRAIL-resistant HCC through the following two mechanisms. First, periplocin induced the expression of DR4 and FADD. Second, the cotreatment of TRAIL and periplocin suppressed several inhibitors of apoptosis (IAPs). Both mechanisms resulted in the activation of caspase 3, 8, and 9 and led to cell apoptosis. In addition, intraperitoneal injection (IP) of periplocin repressed the growth of hepatocellular carcinoma (HCC) in xenograft tumor model in mice. In summary, periplocin sensitized TRAIL-resistant HCC cells to TRAIL treatment and resulted in tumor cell apoptosis and the repression of tumor growth in vivo.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2013 (2013), Article ID 958025 Link to Full Article
Phase II study of viscum fraxini-2 in patients with advanced hepatocellular carcinoma M Mabed1, L El-Helw1 and S Shamaa1
1Hematology and Medical Oncology Unit, Faculty of Medicine, Mansoura University, Mansoura, Egypt
Abstract Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although a wide range of therapeutic options is available, the efficacy of these methods and the prognosis of patients with HCC remain very poor. This study was conducted to evaluate the efficacy and safety of viscum fraxini-2 in patients with chemotherapy–naïve, advanced hepatocellular carcinoma. 23 patients with unrespectable HCC who had received no prior systemic chemotherapy with objectively measurable tumors were enrolled on this study. The mistletoe preparation for the study is an aqueous injectable solution. It contains one milliliter of viscum fraxini in dilution stage–2 (15 mg extract of 20 mg mistletoe herb from ash tree, diluted in di-natrium-mono-hydrogen phosphate, ascorbic acid and water) which is equivalent to 10 000 ng/ml injection ampoules. 2 ampoules of viscum fraxini–2 were administered subcutaneously once weekly. As assessed by conventional imaging criteria, 3 (13.1%) patients have achieved complete response, 2 (8.1%) patients have achieved a partial response. 9 (39.1%) had progressive disease while 9 (39.1%) patients didn't have evaluation of response due to early death. The median overall survival time for all patients was 5 months (range 2–38 months), for those who achieved a CR was 29 months (range 12–38 months) and, for those who achieved a PR was 6.5 months (range 6–7 months). The median progression free survival for all patients was 2 months (range 1–38 months), for those who achieved a CR, it was 29 months (range 8–38 months) and for those who achieved a partial response, it was 5 months (range 4–6 months). No hematologic toxicity has been encountered. The spectrum of non-hematologic toxicity was mild. The WHO toxicity criteria grade 3–4 were 34.8% drug related fever, 13.1% erthyma at injection site and 17.4% pain at the site of injection. No drug related discontinuation or toxic deaths have occurred. Viscum fraxini-2 seems to be particularly promising in patients with advanced HCC, it shows antitumor activity and low toxicity profile. Further studies in combination with other active agents are clearly warranted.
Aloe-emodin novel anticancer Herbal Drug Khemkaran Ahirwar1 * Sanmati K. Jain1
Abstract The electrochemical behaviour of the anticancer herbal drug emodin hydroxyanthraquinone present in Aloe vera leaves has a specific in vitro and in vivo antineuroectodermal tumor activity. The compound does not inhibit the proliferation of normal fibroblasts n or that of hemopoietic progenitor cells. The cytotoxicity mechanism consists of the induction of apoptosis, whereas the selectivity against neuroectodermal tumor cells is founded on a specific energy-dependent pathway of drug incorporation. Natural compounds that have traditionally been used to treat a variety of diseases for hundreds of years (1, 2, 3) . We assayed only those natural compounds that have already been proven to be nontoxic, and we evaluated their efficacy against highly malignant tumors that are not normally included in the classical screening assays.
Conclusion: Aloe-Emodin was able to inhibit cell growth in several tumor cells, including human lung carcinoma, 10 hepatoma, 11 and leukemia cell lines. 13 aloe-emodin shows a high specificity for neuroectodermal tumor cells. 14 one of the important approaches for cancer chemotherapy is to regulate cell-cycle progression. G1/S cell-cycle arrest was found in human hepatoma, 12 glioma, 16 breast, 10 lung, 11 and colon 15 carcinoma cells upon treatment of rhubarb anthraquinones (emodin, 9 aloe-emodin, 13 and rhein 16 The herbal medicines have great importance in the treatment of many diseases. Since herbal medicines are mainly used by Chinese, but now gaining acceptance all over the world and mostly in India. Herbal plants and their derivatives are widely used in the treatment of cancer. The treatment of cancer must include the benefits of botanical medicines. There are many classes of plant-derived cytotoxic natural products and the structural modification studies for further improvement and development of drug. New anticancer drugs derived from research on plant antitumor agents will be continuously discovered. The activities of flavonoids and the synergistic action shown by them with other drugs make them ideal in alternative cancer therapies. The chemopreventive effects that most flavonoids exert are likely to be the sum of their effect on several distinct mechanisms working inside the cell. The flavonoids have been focused for the research since 1930’s but many of them have been used in traditional medicines for thousands of years in eastern countries. Anthraquinones are an important group of bioactive components found in many species of medicinal herbs such as rhubarb, senna, aloe and purslane. Induction of apoptosis is commonly reported among emodin and aloe-emodin, which involve disruption of mitochondria membrane potential, cytochrome c release, and activation of caspase 3. Emodin and aloe-emodin were also able to induce cell-cycle arrest, involving an increase in p53 expression level and accompanied by upregulation of p21. This suggests that emodin could be a promising candidature for the research and development of new anti-tumor drugs.
A homeopathic approach to treat patients with advanced gallbladder, periampullary, and liver carcinomas: a report of 3 cases. Chatterjee A, Biswas J.
Critical Cancer Management Research Centre & Clinic , Kolkata, West Bengal, India .
Abstract Objectives: The authors present 3 cases of various pathologically confirmed malignancies (one gallbladder, one periampullary, and one liver). These patients underwent Psorinum therapy as the primary cancer treatment. Psorinum therapy is a homeopathic approach to treat patients with cancer.
Subjects: According to the American Joint Committee on Cancer tumor, nodes, metastasis system, all 3 patients were diagnosed at Stage IV. Their Karnofsky performance status was between 20% and 50% and their Eastern Cooperative Oncology Group score status was between 3 and 4. In these cases, conventional cancer treatments could not be initiated due to the advanced stage of their disease, poor general health performance status, and their financial constraints.
Interventions and outcome: In these patients, Psorinum-6x was administered orally at a dose of 0.02 mL/kg body weight/day on an empty stomach for a complete course duration of 2 years, along with allopathic and homeopathic supportive treatment. According to the Response Evaluation Criteria in Solid Tumors criteria, complete tumor response occurred in 1 case and partial tumor response occurred in the other 2 cases. All 3 patients remained alive and maintained a stable quality of life for at least 2 years. The patients reported no adverse side-effects from Psorinum-6x.
Conclusions: This report indicates the clinical efficacy of Psorinum therapy in treating those 3 patients. Thorough basic research and well-designed clinical trials should be conducted for further investigation of this homeopathic cancer treatment in order to integrate it into the mainstream of oncology treatments.
Anti-tumor effect of Archidendron lucidum (Benth.) against esophageal cancer, colorectal cancer and hepatoma Chia-Yuan Liu1,2,3#, Yuen-Liang Lai4,5#, Chin-Ping Lin1, Yu-Tse Wu3, Tung-Hu Tsai3## and Yu-Jen Chen1,3,4*
1Department of Medical Research, Mackay Memorial Hospital, Taipei, Taiwan. 2Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan. 3Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan. 4Department of Radiation Oncology, Mackay Memorial Hospital, Taipei, Taiwan. 5Taipei Medical University- Shuang Ho Hospital, Taipei, Taiwan. 6Department of Education and Research, Taipei City Hospital, Taipei, Taiwan.
Abstract Archidenron lucidum is an indigenous medicinal plant in Taiwan used for treatment of inflammatory diseases and cancer. This study was aimed to investigate its anti-cancer effect against gastrointestinal and hepatic malignancy. We found that the 50% effective concentrations of its methanol extract (MEAL) against human esophageal cancer CE81T/VGH, hepatoma HA22T/VGH and murine colorectal cancer CT26 cells were less than 5.0 μg/mL in vitro whereas those of water extract were greater than 30 μg/mL. Cell cycle arrest at G2/M phase was observed in all three cell lines treated with MEAL. Development of hypodiploidy cells suggests that apoptosis might be one of the cell death pathways of CE81T/VGH cells. Intraperitoneal injection with 1.25 mg/kg MEAL significantly inhibited syngeneic CT26 tumor growth in BALB/c mice without obvious toxicity in terms of changes in body weight, leukocyte count and plasma creatinine and alanine aminotransferase (ALT) levels. Higher dose (2.5 mg/kg) MEAL did not further increase the anti-tumor effect, but resulted in elevation of plasma ALT level. Our results indicate that optimal dose of MEAL might possess the anti-tumor effects against esophageal, hepatocellular and colorectal cancers with a relative safety profile. Accordingly, we are purifying effective and less toxic compounds from MEAL.
Source : Journal of Medicinal Plants Research Vol. 5(21), pp. 5221-5229, 9 October, 2011 Link to Full Article
Antiproliferative activity of different extracts from Daphne altaica Pall. on selected cancer cells Murat Kizaibek1,3, Marzia Daniar2, Lin Li2 and Halmurat Upur3*
1Traditional Kazakh Medicine Research Institute of Ili Kazakh Autonomous Prefecture, 835000 Yining, Xinjiang, P. R. China. 2Department of Biochemistry and Molecular Biology, College of Basic Medicine, Xinjiang Medical University, 830011 Urumqi, Xinjiang, P. R. China. 3Faculty of Traditional Uighur Medicine, Xinjiang Medical University, 830011 Urumqi, Xinjiang, P. R. China.
Abstract Daphne altaica Pall. (Thymelaeaceae) is a medicinal plant that has long been used to treat cancer and respiratory ailments in Traditional Kazakh Medicine. In order to systematically evaluate its potential anticancer activity, six extracts of different polarity, namely: aqueous, n-butanol, ethyl acetate, chloroform, petroleum ether and ethanol extracts were obtained from this plant and they were tested for their antiproliferative effects on four human cancer cell lines: esophageal squamous cell carcinoma, gastric carcinoma, hepatoma and cervical carcinoma cells. Results from the proliferation assay showed that all extracts, except for aqueous extract, exhibited a dose-dependent growth inhibitory effect on all cancer cell lines. Of these extracts, two fractions obtained from partitioning of ethanol extract, namely: chloroform extract and ethyl acetate extract, could be considered a potential source of anticancer compounds. Further studies are necessary for identification and chemical characterization of the active principles.
Conclusion The results of this study represent the first evidence that barks of D. altaica possess effective antiproliferative activities on human cancer cells. Future phytochemical investigations on this medicinal plant should be encouraged.
Source : Journal of Medicinal Plants Research Vol. 5(15), pp. 3448-3452, 4 August, 2011 Link to Full Article
Ds-echinoside A, a new triterpene glycoside derived from sea cucumber, exhibits antimetastatic activity via the inhibition of NF-κB-dependent MMP-9 and VEGF expressions
Qin Zhao, Zhi-dong Liu, Yong Xue, Jing-feng Wang,†‡ Hui Li, Qing-juan Tang, Yu-ming Wang, Ping Dong, and Chang-hu Xue†‡ College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
Ds-echinoside A (DSEA), a non-sulfated triterpene glycoside, was isolated from the sea cucumber Pearsonothuria graeffei. In vitro and in vivo investigations were conducted on the effects of DSEA on tumor cell adhesion, migration, invasion, and angiogenesis. In this study, we found that DSEA inhibited the proliferation of human hepatocellular liver carcinoma cells Hep G2, with a half-maximal inhibitory concentration (IC50) of 2.65 μmol/L, and suppressed Hep G2 cell adhesion, migration, and invasion in a dose-dependent manner. DSEA also reduced tube formation of human endothelial cells ECV-304 on matrigel in vitro and attenuated neovascularization in the chick embryo chorioallantoic membrane (CAM) assay in vivo. Immunocytochemical analysis revealed that DSEA significantly decreased the expression of matrix metalloproteinase-9 (MMP-9), which plays an important role in the degradation of basement membrane in tumor metastasis and angiogenesis. DSEA also increased the protein expression level of tissue inhibitor of metalloproteinase-1 (TIMP-1), an important regulator of MMP-9 activation. From the results of Western blotting, the expressions of nuclear factor-kappa B (NF-κB) and vascular endothelial growth factor (VEGF) were found to be remarkably reduced by DSEA. These findings suggest that DSEA exhibits a significant anti-metastatic activity through the specific inhibition of NF-κB-dependent MMP-9 and VEGF expressions.
In conclusion, the present study provides evidence that DSEA possesses marked anti-metastatic activity. We have shown that DSEA plays a role in the inhibition of Hep G2 cell migration, invasion, and angiogenesis through suppression of VEGF and MMP-9 and enhancement of TIMP-1 protein expression by blocking the NF-κB signaling pathway. To our knowledge, this is the first report demonstrating the anti-metastatic activity of a nonsulfated triterpene glycoside isolated from P. graeffei, and providing a scientific basis for its application in therapeutic intervention against tumor progression.
Source : J Zhejiang Univ Sci B. 2011 July; 12(7): 534–544. doi: 10.1631/jzus.B1000217 Link to Full Article
Effect of Coffee and Green Tea Consumption on the Risk of Liver Cancer: Cohort Analysis by Hepatitis Virus Infection Status
Manami Inoue1, Norie Kurahashi1, Motoki Iwasaki1, Taichi Shimazu1, Yasuhito Tanaka2,Masashi Mizokami2, Shoichiro Tsugane1 and for the Japan Public Health Center-Based Prospective Study Group
Epidemiology and Prevention Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan and 2Department of Clinical Molecular Informative Medicine, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
In spite of their anticarcinogenic potential, the effect of coffee and green tea consumption on the risk of liver cancer has not been clarified prospectively in consideration of hepatitis C (HCV) and B virus (HBV) infection. We examined whether coffee and green tea consumption was associated with a reduced risk of liver cancer by hepatitis virus infection status in the Japan Public Health Center-Based Prospective Study Cohort II. A total of 18,815 subjects ages 40 to 69 years participating in a questionnaire and health checkup survey in 1993 to 1994 were followed for the incidence of liver cancer through 2006. A total of 110 cases of liver cancer were newly documented. Hazard ratios for coffee and green tea consumption categories were calculated with a Cox proportional hazards model. Compared with almost never drinkers, increased coffee consumption was associated with a reduced risk of liver cancer in all subjects (hazard ratio for <1, 1-2, and ≥3 cups/d; Ptrend = 0.67, 0.49, 0.54, and 0.025). A similar risk tendency was observed in those with either or both HCV and HBV infection. In contrast, no association was observed between green tea consumption and the risk of liver cancer in all subjects. Our results suggest that coffee consumption may reduce the risk of liver cancer regardless of HCV and HBV infection status, whereas green tea may not reduce this risk
In vitro and in vivo antitumor activity of Macrothelypteris torresiana and its acute/subacute oral toxicity by X.H. Huang, P.C. Xiong, C.M. Xiong, Y.L. Cai, A.H. Wei, J.P. Wang, X.F. Liang, J.L. Ruan
The aim of this study was to evaluate the antitumor potential of Macrothelypteris torresiana by studying in vitro antitumor activity of the protoapigenone, as well as in vivo antitumor activity and acute/subacute oral toxicity of the total flavonoid fraction from the roots of M. torresiana. Considering that the protoapigenone is a main constituent of the total flavonoid fraction and it might play a key role in the antitumor activity of M. torresiana, the MTT assay was used to investigate the in vitro antitumor activity of the protoapigenone. Our study revealed that the protoapigenone of M. torresiana showed significant antitumor activity towards Hep G2, Tca-8113, MCF-7, M5 and K562 with [IC.sub.50] values of 2.3, 0.6, 0.8, 0.3 and 0.9 [mu]g/ml, respectively. The antitumor potential of the total flavonoid fraction was evaluated using preparations 1, 2 and 3, which were prepared by total flavonoid fraction directly diluted with sterile saline, dissolved using sodium carboxymethyl cellulose (CMC-Na) and included by hydroxypropyl-[beta]-cyclodextrin, respectively. These were investigated in vivo using mouse sarcoma S-180 in BALB/c mice after completing tumor inoculation for 24 h. Pronounced antitumor activity was observed in the treated groups for preparations 2 and 3, and the high and medium doses in particular showed very high inhibition ratio of tumor growth (<50%). No significant difference was observed when compared to the positive control group (5-fluorouracil). The acute/subacute oral toxicity test was performed, and the results of acute oral toxicity showed that the [LD.sub.50] values of preparations 2 and 3 were 2.76 and 0.87 g/kg body wt., respectively. According to the results of the subacute oral toxicity study, the total flavonoid fraction had low toxicity. The overall results of this study suggest that the total flavonoid fraction from the roots of M. torresiana shows significant antitumor activity and represents a potential source of medicine for the treatment of cancer.
NOTE Macrothelypteris torresiana (Gaud.) Ching (Thelypteridaceae) is widely distributed in the south of China and has been used as folk medicine mainly for the treatment of diseases such as hydropsy and traumatic bleeding (Institute of Botany, 1976; Ding, 1982). This recent scientific attention was because of some unusual flavonoids isolated from the species M. torresiana showing significant antitumor activities. Among of them, a unique flavonoid named protoapigenone showed significant antitumor activity against human cancer cell lines Hep G2, Hep 3B (liver), MCF-7 (breast), A549 (lung) and MDA-MB-231 with [IC.sub.50] values of 1.60, 0.23, 0.78, 3.88 and 0.27 ([mu]g/ml, respectively (Lin et al., 2005).
Anti-proliferative effects of raw and steamed extracts of Panax notoginseng and its ginsenoside constituents on human liver cancer cells Ding-Fung Toh , Dhavalkumar Narendrabhai Patel , Eric Chun-Yong Chan , Alvin Teo , Soek-Ying Neo and Hwee-Ling Koh
Background Panax notoginseng is a potential source of anticancer compounds. This study aims to investigate the effects of steaming on the chemical profile of P. notoginseng and the anti-proliferative effects of P. notoginseng on liver cancer cells.
Methods Samples of powdered raw P. notoginseng roots were steamed for various durations. Extracts of the raw and steamed samples were subjected to ultra-high pressure liquid chromatography / mass spectrometry (UHPLC-MS) analysis for chemical profiling. The anti-proliferative effects on three human liver cancer cells, namely SNU449, SNU182 and HepG2, were evaluated using colorimetric WST-1 assay.
Results Steaming changed chromatographic and pharmacological profiles of P. notoginseng, causing differences in activities such as inhibition of cancer growth. Steamed P. notoginseng exhibited greater anti-proliferative effects against liver cancer cells (SNU449, SNU182 and HepG2) than its raw form; steaming up to 24 hours increased bioactivities. Steaming increased the concentrations of ginsenoside Rh2, Rk1, Rk3 and 20S-Rg3 and enhanced growth inhibition of liver cancer cells. Conclusion Steaming changes the chemical profile as well as anti-cancer biological activities of P. notoginseng. Steamed P. notoginseng contains potential compounds for the treatment of liver cancer.
Psorinum Therapy in Treating Stomach, Gall Bladder, Pancreatic, and Liver Cancers: A Prospective Clinical Study Aradeep Chatterjee,1 Jaydip Biswas,2 Ashim Chatterjee,1 Sudin Bhattacharya,2 Bishnu Mukhopadhyay,3 and Syamsundar Mandal2
1Critical Cancer Management Research Centre & Clinic, 381 S K Deb Road, West Bengal, Kolkata 700 048, India 2Chittaranjan National Cancer Institute, Kolkata 700 026, India 3National Institute of Technology, Durgapur 713209, India
We prospectively studied the clinical efficacy of an alternative cancer treatment “Psorinum Therapy” in treating stomach, gall bladder, pancreatic and liver cancers. Our study was observational, open level and single arm. The participants' eligibility criteria included histopathology/cytopathology confirmation of malignancy, inoperable tumor, and no prior chemotherapy or radiation therapy. The primary outcome measures of the study were (i) to assess the radiological tumor response (ii) to find out how many participants survived at least 1 year, 2 years, 3 years, 4 years and finally 5 years after the beginning of the study considering each type of cancer. Psorinum-6x was administered orally to all the participants up to 0.02 ml/Kg body weight as a single dose in empty stomach per day for 2 years along with allopathic and homeopathic supportive cares. 158 participants (42 of stomach, 40 of gall bladder, 44 of pancreatic, 32 of liver) were included in the final analysis of the study. Complete tumor response occurred in 28 (17.72%) cases and partial tumor response occurred in 56 (35.44%) cases. Double-blind randomized controlled clinical trial should be conducted for further scientific exploration of this alternative cancer treatment.
.....The limitation of this study is that it did not have any placebo or treatment control arm; therefore, it cannot be concluded that Psorinum Therapy is effective in improving the survival and the quality of life of the participants due to the academic rigours of the scientific clinical trials. This study also cannot rule out the effects of the implemented allopathic and homeopathic supportive measures in the observed results. However, the results of the study showed a fair number of complete and partial tumor responses along with impressive survival outcomes in difficult to treat cancer types. Therefore, randomized double-blind clinical trial, detailed molecular, pharmacokinetics, and pharmacodynamics studies should be conducted for further scientific exploration of this alternative cancer treatment to determine if it can be integrated into the mainstream oncology.
Source : Evidence-Based Complementary and Alternative Medicine Volume 2011 (2011), Article ID 724743, 7 pages doi:10.1155/2011/724743 LINK TO FULL ARTICLE
Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells. in vitro Wiratchanee Mahavorasirikul1, Vithoon Viyanant1, Wanna Chaijaroenkul1, Arunporn Itharat2, Kesara Na-Bangchang1* 1Graduate Program in Biomedical Sciences, Thammasat University (Rangsit Campus), Pathumtani 12121, Thailand 2Applied Thai Traditional Medicine Center, Thammasart University (Rangsit Campus), Pathumtani 12121, Thailand
Abstract Background: Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro.
Methods: Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC50 (concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated. Results: The extracts from seven plant species (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, Ligusticum sinense, Mimusops elengi) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, and Pra-Sa-Prao-Yhairecipe) showed potent cytotoxic activity with mean IC50 values of 24.09, 37.36, 34.26,40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC50 ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC50 ranged from 9.67 to 115.47 μg/ml. The only promising extract was from Zingiber officinal (IC50 = 9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC50 = 757 micromolar). The extract from Atractylodes lancea appears to be both the most potent and most selective against cholangiocarcinoma (IC50 = 24.09 μg/ml, SI = 8.6).
Conclusions: The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line HepG2 appears to be the most resistant to the tested extracts.
Source : BMC Complementary and Alternative Medicine LINK TO FULL ARTICLE Cholangiocarcinoma is a cancerous (malignant) growth in one of the ducts that carries bile from the liver to the small intestine.
Green tea consumption and the risk of liver cancer in Japan: the Ohsaki Cohort study Journal
Cancer Causes and Control PublisherSpringer Netherlands ISSN0957-5243 (Print) 1573-7225 (Online) CategoryOriginal paper DOI10.1007/s10552-009-9388-x Subject CollectionMedicine SpringerLink DateFriday, September 18, 2009
Methanol Extract of the Seaweed Gloiopeltis furcata Induces G2/M Arrest and Inhibits Cyclooxygenase-2 Activity in Human Hepatocarcinoma HepG2 Cells Song Ja Bae1 and Yung Hyun Choi2,3*
1.Department of Food Science and Nutrition, Silla University and Marine Biotechnology center for Bio-Functional Material Industries, Busan 617-736, Korea 2Department of Biochemistry, Dongeui University College of Oriental Medicine, Busan 614-052, South Korea 3Department of Biomaterial Control, Dongeui University Graduate School, Busan 614-052, South Korea
It was previously reported that a methanol extract of Gloiopeltis furcata (MEGF), a kind of edible seaweed, inhibited the growth of several human cancer cell lines. In the present study, the effect of MEGF on the growth of human hepatocarcinoma HepG2 cells and its effect on the cyclooxygenases (COXs) expression were investigated. MEGF markedly reduced the viability of HepG2 cells and induced the G2/M arrest of the cell cycle in a concentration dependent manner. These effects were associated with the down-regulation of cyclin A, up-regulation of cyclin-dependent kinase (Cdk) inhibitor p21 (WAF1/CIP1) and dephosphorylation of Cdc25C. Furthermore, it was found that MEGF decreased the levels of COX-2 mRNA and protein expression without significant changes in the levels of COX-1, which was correlated with a decrease in prostaglandin E2 (PGE2) synthesis. These findings indicate that MEGF may have a possible therapeutic potential in hepatoma cancer patients.