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Su-Yu Chien, Ching-Hui Hsu, Chia-Chieh Lin, Yi-Ching Chuang, Yu-Sheng Lo, Yi-Ting Hsi, Ming-Ju Hsieh, Mu-Kuan Chen
Nasopharyngeal carcinoma (NPC), a tumor arising from epithelial cells that cover the surface and line the nasopharynx, is a rare malignancy worldwide but is prevalent in certain geographical areas, such as Southern Asia (Taiwan, Hong Kong, Singapore, Malaysia, and Southern China) and North Africa. Despite advances in diagnostic techniques and improvements in treatment modalities, the prognosis of NPC remains poor. Therefore, an effective chemotherapy regimen that enhances tumor sensitivity to chemotherapeutics is urgently required...
April 6, 2017: Environmental Toxicology
Paulraj Raja Singh, Elayapillai Sugantha Priya, Solaimuthu Balakrishnan, Ramachandran Arunkumar, Govindaraj Sharmila, Manikkam Rajalakshmi, Jagadeesan Arunakaran
Prostate cancer is most common malignancy among men in the world. PI3K-Akt signaling appears to be critical to prostate cancer cell proliferation and survival. Our earlier study reveals that nimbolide (2 µM) prevents cell survival via IGF signaling pathway through PI3K/Akt and induces apoptosis in PC-3 cell line. Akt mediates the phosphorylation and activation of mTOR that plays a critical role in the regulation of protein translation and synthesis, angiogenesis, and cell cycle progression. The present study was aimed to investigate the effect of nimbolide on tPI3K, tAkt, pAkt, tmTOR, GSK3β, pGSK3β, PCNA, c-Myc, Cyclin D1, and Survivin protein levels by western blot analysis...
March 2017: Molecular and Cellular Biochemistry
P Raja Singh, E Sugantha Priya, S Balakrishnan, R Arunkumar, G Sharmila, M Rajalakshmi, J Arunakaran
BACKGROUND: Prostate cancer is the most prominent cancer in men, experiencing a relapse in disease often express high serum TNF-α levels. It has been correlated with increased cell survival and proliferation of prostate cancer cells. Previous studies reported that nimbolide, a terpenoid derived from the leaves and flowers of neem tree inhibits cancer growth through selective modulation of cell signaling pathways linked to inflammation, survival, proliferation, angiogenesis and metastasis...
December 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Prodipta Sarkar, Saurabh Acharyya, Anirban Banerjee, Amarendra Patra, Karthika Thankamani, Hemanta Koley, Prasanta K Bag
Staphylococcus aureus is a leading aetiologic agent of nosocomial- and community-acquired infectious diseases worldwide. The public health concern regarding staphylococcal infections is inflated by the increasing occurrence of multidrug-resistant strains, e.g. multidrug- and meticillin-resistant S.aureus (MDR MRSA). This study was designed to evaluate the intracellular killing, membrane-damaging and biofilm-inhibitory activities of nimbolide isolated from Azadirachta indica against MDR MRSA. In vitro antibacterial activity of nimbolide was determined by performing MIC, minimal bactericidal concentration (MBC) and time-kill kinetic studies...
October 2016: Journal of Medical Microbiology
Subash C Gupta, Simone Reuter, Kanokkarn Phromnoi, Byoungduck Park, Padmanabhan S Hema, Mangalam Nair, Bharat B Aggarwal
No abstract text is available yet for this article.
August 5, 2016: Journal of Biological Chemistry
Ji Yeon Seo, Changhyun Lee, Sung Wook Hwang, Jaeyoung Chun, Jong Pil Im, Joo Sung Kim
Nimbolide is a limonoid extracted from neem tree (Azadirachta indica) that has antiinflammatory properties. The effect of nimbolide on the nuclear factor-kappa B (NF-κB) pathway in intestinal epithelial cells (IECs), macrophages and in murine colitis models was investigated. The IEC COLO 205, the murine macrophage cell line RAW 264.7, and peritoneal macrophages from interleukin-10-deficient (IL-10(-/-) ) mice were preconditioned with nimbolide and then stimulated with tumor necrosis factor-α (TNF-α) or lipopolysaccharide...
October 2016: Phytotherapy Research: PTR
Chantana Chantana, Chavi Yenjai, Prasert Reubroycharoen, Pornthip Waiwut
Tumor necrosis factor (TNF-α), an inflammatory cytokine that plays an important role in the control of cell proliferation, differentiation, and apoptosis, has previously been used in anti-cancer therapy. However, the therapeutic applications of TNF-α are largely limited due to its general toxicity and anti-apoptotic influence. To overcome this problem, the present study focused on the effect of active constituents isolated from a medicinal plant on TNF-α-induced apoptosis in human colon adenocarcinoma (HT-29) cells...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
Jay Morris, Yuan Fang, Keya De Mukhopdhyay, Michael J Wargovich
Aerodigestive cancers are on an increasing level in both occurrence and mortality. A major cause in many of these cancers is disruption of the inflammatory pathway, leading to increased cell proliferation, and epigenetic silencing of normal regulatory genes. Here we review the research on several natural products: silibinin, silymarin, quercetin, neem & nimbolide, gingerol, epigallatecatechin-3- gallate, curcumin, genistein and resveratrol conducted on aerodigestive cancers. These types of cancers are primarily those from oral cavity, esophagus/windpipe, stomach, small and large intestine, colon/rectum and bile/pancreas tissues...
February 2016: Current Pharmacology Reports
Lingzhi Wang, Do Dang Khoa Phan, Jingwen Zhang, Pei-Shi Ong, Win Lwin Thuya, Ross Soo, Andrea Li-Ann Wong, Wei Peng Yong, Soo Chin Lee, Paul Chi-Lui Ho, Gautam Sethi, Boon Cher Goh
Nimbolide is one of the main components in the leaf extract of Azadirachta indica (A. indica). Accumulating evidence from various in vitro and in vivo studies indicates that nimbolide possesses potent anticancer activity against several types of cancer and also shows potential chemopreventive activity in animal models. The main mechanisms of action of nimbolide include anti-proliferation, induction of apoptosis, inhibition of metastasis and angiogenesis, and modulation of carcinogen-metabolizing enzymes. Although multiple pharmacodynamic (PD) studies have been carried out, nimbolide is still at the infant stage in the drug development pipeline due to the lack of systematic pharmacokinetic (PK) studies and long-term toxicological studies...
July 12, 2016: Oncotarget
Josephraj Sophia, Kranthi Kiran Kishore T, Jaganathan Kowshik, Rajakishore Mishra, Siddavaram Nagini
Glycogen synthase kinase-3β (GSK-3β), a serine/threonine kinase is frequently inactivated by the oncogenic signalling kinases PI3K/Akt and MAPK/ERK in diverse malignancies. The present study was designed to investigate GSK-3β signalling circuits in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis model and the therapeutic potential of the neem limonoid nimbolide. Inactivation of GSK-3β by phosphorylation at serine 9 and activation of PI3K/Akt, MAPK/ERK and β-catenin was associated with increased cell proliferation and apoptosis evasion during stepwise evolution of HBP carcinomas...
February 23, 2016: Scientific Reports
Ramadevi Subramani, Elizabeth Gonzalez, Arunkumar Arumugam, Sushmita Nandy, Viviana Gonzalez, Joshua Medel, Fernando Camacho, Andrew Ortega, Sandrine Bonkoungou, Mahesh Narayan, Alok kumar Dwivedi, Rajkumar Lakshmanaswamy
The mortality and morbidity rates of pancreatic cancer are high because of its extremely invasive and metastatic nature. Its lack of symptoms, late diagnosis and chemo-resistance and the ineffective treatment modalities warrant the development of new chemo-therapeutic agents for pancreatic cancer. Agents from medicinal plants have demonstrated therapeutic benefits in various human cancers. Nimbolide, an active molecule isolated from Azadirachta indica, has been reported to exhibit several medicinal properties...
January 25, 2016: Scientific Reports
Jingwen Zhang, Kwang Seok Ahn, Chulwon Kim, Muthu K Shanmugam, Kodappully Sivaraman Siveen, Frank Arfuso, Ramar Perumal Samym, Amudha Deivasigamanim, Lina Hsiu Kim Lim, Lingzhi Wang, Boon Cher Goh, Alan Prem Kumar, Kam Man Hui, Gautam Sethi
AIMS: Prostate cancer (PCa) is one of the most commonly diagnosed cancers worldwide. Currently available therapies for metastatic PCa are only marginally effective, hence novel treatment modalities are urgently required. Considerable evidence(s) suggest that deregulated activation of oncogenic transcription factor, signal transducer and activator of transcription 3 (STAT3) plays a pivotal role in the development and progression of PCa. Thus, agents that can abrogate STAT3 activation could form the basis of novel therapy for PCa patients...
April 10, 2016: Antioxidants & Redox Signaling
Saurabh Bundela, Anjana Sharma, Prakash S Bisen
Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier...
2015: PloS One
Ju-Fang Liu, Chun-Han Hou, Feng-Ling Lin, Ya-Ting Tsao, Sheng-Mou Hou
Osteosarcoma (OS) is a primary malignant tumor of bone and is most prevalent in children and adolescents. OS is frequently associated with pulmonary metastasis, which is the main cause of OS-related mortality. OS has a poor prognosis and is often unresponsive to conventional chemotherapy. In this study, we determined that Nimbolide, a novel anti-cancer therapy, acts by modulating multiple mechanisms in osteosarcoma cells. Nimbolide induces apoptosis by increasing endoplasmic reticulum (ER) stress, mitochondrial dysfunction, accumulation of reactive oxygen species (ROS), and finally, caspase activation...
2015: International Journal of Molecular Sciences
Yi-Hsien Hsieh, Chien-Hsing Lee, Hsiao-Yun Chen, Shu-Ching Hsieh, Chia-Liang Lin, Jen-Pi Tsai
Nimbolide is a tetranortriterpenoid isolated from the leaves and flowers of Azadirachta indica which has been shown to exhibit anticancer, antioxidant, anti-inflammatory, and anti-invasive properties in a variety of cancer cells. However, the anti-tumor effect on human renal cell carcinoma (RCC) cells is unknown. In this study, we found that nimbolide treatment had a cytotoxic effect on 786-O and A-498 RCC cells in a dose-dependent manner. According to flow cytometric analysis, nimbolide treatment resulted in G2/M arrest in 786-O and A-498 cells accompanied with an increase in the phosphorylation status of p53, cdc2, cdc25c, and decreased expressions of cyclin A, cyclin B, cdc2, and cdc25c...
September 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Mohamed Abdo Rizk, Shimaa Abd El-Salam El-Sayed, Mohamed Alaa Terkawi, Mohamed Ahmed Youssef, El Said El Shirbini El Said, Gehad Elsayed, Sabry El-Khodery, Maged El-Ashker, Ahmed Elsify, Mosaab Omar, Akram Salama, Naoaki Yokoyama, Ikuo Igarashi
A rapid and accurate assay for evaluating antibabesial drugs on a large scale is required for the discovery of novel chemotherapeutic agents against Babesia parasites. In the current study, we evaluated the usefulness of a fluorescence-based assay for determining the efficacies of antibabesial compounds against bovine and equine hemoparasites in in vitro cultures. Three different hematocrits (HCTs; 2.5%, 5%, and 10%) were used without daily replacement of the medium. The results of a high-throughput screening assay revealed that the best HCT was 2...
2015: PloS One
Perumal Elumalai, Jagadeesan Arunakaran
Cancer is the most dreaded disease in human and also major health problem worldwide. Despite its high occurrence, the exact molecular mechanisms of the development and progression are not fully understood. The existing cancer therapy based on allopathic medicine is expensive, exhibits side effects; and may also alter the normal functioning of genes. Thus, a non-toxic and effective mode of treatment is needed to control cancer development and progression. Some medicinal plants offer a safe, effective and affordable remedy to control the cancer progression...
December 2014: Genomics & Informatics
K Chitta, A Paulus, T R Caulfield, S Akhtar, M-K K Blake, S Ailawadhi, J Knight, M G Heckman, A Pinkerton, A Chanan-Khan
Neem leaf extract (NLE) has medicinal properties, which have been attributed to its limonoid content. We identified the NLE tetranorterpenoid, nimbolide, as being the key limonoid responsible for the cytotoxicity of NLE in various preclinical models of human B-lymphocyte cancer. Of the models tested, Waldenströms macroglobulinemia (WM) cells were most sensitive to nimbolide, undergoing significant mitochondrial mediated apoptosis. Notably, nimbolide toxicity was also observed in drug-resistant (bortezomib or ibrutinib) WM cells...
November 7, 2014: Blood Cancer Journal
P Elumalai, A Brindha Mercy, R Arunkamar, G Sharmila, F A Bhat, S Balakrishnan, P Raja Singh, J Arunakaran
OBJECTIVES: Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death in women, worldwide. Urokinase type plasminogen activator (uPA) is a serine protease that is involved in cancer progression, especially invasion and metastasis of breast cancer. Nimbolide is a potent cytotoxic limnoid isolated from Azadirachta indica. Our previous studies have shown that nimbolide elicits pleiotropic effects on breast cancer cells; however, its roles in invasion and migration have not previously been fully elucidated...
December 2014: Cell Proliferation
Fang Hao, Sandeep Kumar, Neelu Yadav, Dhyan Chandra
Azadirachta indica, also known as neem, is commonly found in many semi-tropical and tropical countries including India, Pakistan, and Bangladesh. The components extracted from neem plant have been used in traditional medicine for the cure of multiple diseases including cancer for centuries. The extracts of seeds, leaves, flowers, and fruits of neem have consistently shown chemopreventive and antitumor effects in different types of cancer. Azadirachtin and nimbolide are among the few bioactive components in neem that have been studied extensively, but research on a great number of additional bioactive components is warranted...
August 2014: Biochimica et Biophysica Acta
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