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Acetogenins AND Cancer

Asif Khurshid Qazi, Jawed A Siddiqui, Rahat Jahan, Sanjib Chaudhary, Larry A Walker, Zafar Syed, Dwight T Jones, Surinder K Batra, Muzafar A Macha
Cancer remains a leading cause of death in the United States and around the world. Although the current synthetic inhibitors used in targeted therapies have improved patient prognosis, toxicity and development of resistance to these agents remain a challenge. Plant-derived natural products and their derivatives have historically been used to treat various diseases, including cancer. Several leading chemotherapeutic agents are directly or indirectly based on botanical natural products. Beyond these important drugs, however, a number of crude herbal or botanical preparations have also shown promising utility for cancer and other disorders...
February 15, 2018: Carcinogenesis
Noraziah Nordin, Nazia Abdul Majid, Rozana Othman, Fatima Abdelmutaal Ahmed Omer, Muhammad Nazil Afiq Nasharuddin, Najihah Mohd Hashim
Plagioneurin B belongs to acetogenin group has well-established class of compounds. Acetogenin group has attracted worldwide attention in the past few years due their biological abilities as inhibitors for several types of tumour cells. Plagioneurin B was isolated via conventional chromatography and tested for thorough mechanistic apoptosis activity on human ovarian cancer cells (CAOV-3). Its structure was also docked at several possible targets using Autodock tools software. Our findings showed that plagioneurin B successfully inhibits the growth of CAOV-3 cells at IC50 of 0...
February 12, 2018: Apoptosis: An International Journal on Programmed Cell Death
Mohamad Norisham Mohamad Rosdi, Shahkila Mohd Arif, Mohamad Hafizi Abu Bakar, Siti Aisyah Razali, Razauden Mohamed Zulkifli, Harisun Ya'akob
Annona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies. A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins...
January 2018: Apoptosis: An International Journal on Programmed Cell Death
Yahaya Gavamukulya, Fred Wamunyokoli, Hany A El-Shemy
Annona muricata (A. muricata) is a tropical plant species belonging to family Annonaceae and known for its many medicinal uses. This review focuses on the research history of its traditional uses, phytochemicals, pharmacological activities, toxicological aspects of the extracts and isolated compounds, as well as the in vitro propagation studies with the objective of stimulating further studies on this plant for human consumption and treatment. A. muricata extracts have been identified in tropical regions to traditionally treat diverse conditions ranging from fever to diabetes and cancer...
September 2017: Asian Pacific Journal of Tropical Medicine
Murdani Abdullah, Ari Fahrial Syam, Sofy Meilany, Bayu Laksono, Oryza Gryagus Prabu, Heri Setiyo Bekti, Lili Indrawati, Dadang Makmun
Annona muricata, commonly known as soursop, contains annonacin, acetogenin, and polyphenol which are known to have chemopreventive effects on cancer. In this study, we tend to evaluate the apoptosis-inducing effect of soursop (Annona muricata) leaf extract on the colorectal cancer cell line COLO-205 through the activities of caspase-3 which is a marker of cell apoptosis. Cell cultures were incubated with soursop leaf with a concentration of 10 μg/ml and then compared with those of the incubated positive control leucovorin 10 μg/ml and placebo as a negative control...
2017: Gastroenterology Research and Practice
Yan Li, Jianbin Ye, Zhongbiao Chen, Junjie Wen, Fei Li, Pengpeng Su, Yanqing Lin, Bingxin Hu, Danlin Wu, Lijun Ning, Qi Xue, Hongxiang Gu, Yunshan Ning
BACKGROUND: Gastric cancer (GC) is a global health problem because of limited treatments and poor prognosis. Annonaceous acetogenins (ACGs) has been reported to exert anti-tumorigenic effects in cancer, yet the mechanism underlying its effects on GC remains largely unknown. Notch signaling plays a critical role in cell proliferation, differentiation and apoptosis. Therefore, it may contribute to the development of GC. This study aims to explore the role of Notch2 in ACGs' activities in GC cells...
March 28, 2017: Oncotarget
Akinobu Akatsuka, Naoto Kojima, Mutsumi Okamura, Shingo Dan, Takao Yamori
Previously we synthesized JCI-20679, a novel thiophene-3-carboxamide analog of annonaceous acetogenins which have shown potent antitumor activity, with no serious side effects, in mouse xenograft models. In this study, we investigated the antitumor mechanism of JCI-20679. The growth inhibition profile (termed "fingerprint") of this agent across a panel of 39 human cancer cell lines (termed "JFCR39") was measured; this fingerprint was analyzed by the COMPARE algorithm utilizing the entire drug sensitivity database for the JFCR39 panel...
August 2016: Pharmacology Research & Perspectives
Chengyao Ma, Qiwen Wang, Yeye Shi, Yue Li, Xunan Wang, Xiang Li, Yong Chen, Jianwei Chen
Two new annonaceous acetogenins squamocin P (2) and annosquatin III (3) and one new ACG precursor dieporeticenin B (1) along with five known precursors (4-8) were isolated from the seeds of Annona squamosa. Their structures were ascertained by chemical methods and various spectral evidences. These compounds showed inhibitory effects against three multidrug-resistant (MDR) cancer cell lines. Compound 2 and 3 displayed selective cytotoxicity against SMMC 7721/T (IC50 0.435 and 1.79 μM) and MCF-7/ADR (IC50 values 3...
September 2017: Natural Product Research
Yong Chen, Yayun Chen, Yeye Shi, Chengyao Ma, Xunan Wang, Yue Li, Yunjie Miao, Jianwei Chen, Xiang Li
CONTEXT: Custard apple (Annona squamosa Linn.) is an edible tropical fruit, and its seeds have been used to treat "malignant sore" (cancer) and other usage as insecticide. A comparison of extraction processes, chemical composition analysis and antitumor activity of A. squamosa seed oil (ASO) were investigated. MATERIALS AND METHODS: The optimal extraction parameters of ASO were established by comparing percolation, soxhlet, ultrasonic and SFE-CO2 extraction methods...
December 4, 2016: Journal of Ethnopharmacology
Usein M Dzhemilev, Vladimir A D'yakonov, Regina A Tuktarova, Lilya U Dzhemileva, Svetlana R Ishmukhametova, Milyausha M Yunusbaeva, Armin de Meijere
An original synthesis of the acetogenin muricadienin, the bioprecursor of solamin, has been developed. The key step in the five-step 41% overall yield synthesis is the catalytic cross-cyclomagnesiation reaction of functionally substituted 1,2-dienes with EtMgBr in the presence of Cp2TiCl2 and magnesium metal. It has been demonstrated for the first time that muricadienin exhibits a moderate in vitro inhibitory activity against topoisomerases I and IIα, key cell cycle enzymes. Using flow cytometry, muricadienin was shown to have high cytotoxicity toward the HEK293 kidney cancer cells (IC50 0...
August 26, 2016: Journal of Natural Products
Jingyi Hong, Yanhong Li, Yijing Li, Yao Xiao, Haixue Kuang, Xiangtao Wang
Annonaceous acetogenins (ACGs) have shown superior antitumor activity against a variety of cancer cell lines, but their clinical application has been limited by their poor solubility. In this study, ACGs-nanosuspensions (NSps) were successfully prepared by a precipitation ultrasonic method using monomethoxypoly (ethylene glycol)2000-poly (ε-caprolactone)2000 (mPEG2000-PCL2000) as a stabilizer. The resultant ACGs-NSps had a mean particle size of 123.2 nm, a zeta potential of -20.17 mV, and a high drug payload of 73...
2016: International Journal of Nanomedicine
Fei Yuan, Ganggang Bai, Yunjie Miao, Yong Chen, Xiang Li, Jianwei Chen
CONTEXT: Multidrug resistance (MDR) is a major obstacle to efficient therapy of cancers. It is a prime concern for researchers to find compounds with anti-proliferative activity on MDR cell lines. In recent years, annonaceous acetogenins (ACGs) were reported to have anti-proliferative activity. However, the underlying mechanisms are still unknown. OBJECTIVE: This study determines the mechanisms of anti-proliferative activity induced by Annosquacin B (AB) against MCF-7/ADR cells...
December 2016: Pharmaceutical Biology
Keerthana Prabhakaran, Gnanam Ramasamy, Uma Doraisamy, Jayakanthan Mannu, Rajamani K, Jayadeepa Rajamani Murugesan
BACKGROUND: Plants became the basis of traditional medicine system throughout the world for thousands of years and continue to provide mankind with new remedies. Annona muricata, the plant of Annonaceae family, is also known as sour sop or Graviola. In recent years, many compounds have been reported and have gained organic chemist's and biochemist's attention because of their novel structure and wide range of bioactivity. Local populations have used the bark, leaves, roots, fruit, seeds and flowers for thousands of years to treat everything from arthritis to liver problems...
2016: Current Pharmaceutical Design
Jingyi Hong, Yanhong Li, Yao Xiao, Yijing Li, Yifei Guo, Haixue Kuang, Xiangtao Wang
Annonaceous acetogenins (ACGs) have exhibited antitumor activity against various cancers. However, these substances' poor solubility has limited clinical applications. In this study, hydroxypropyl-beta-cyclodextrin (HP-β-CD) and soybean lecithin (SPC) were self-assembled into an amphiphilic complex. ACGs nanosuspensions (ACGs-NSps) were prepared with a mean particle size of 144.4nm, a zeta potential of -22.9mV and a high drug payload of 46.17% using this complex as stabilizer. The ACGs-NSps demonstrated sustained release in vitro and good stability in plasma as well as simulated gastrointestinal fluid, and met the demand of both intravenous injection and oral administration...
September 1, 2016: Colloids and Surfaces. B, Biointerfaces
Priya Antony, Ranjit Vijayan
Apoptosis is a highly regulated process crucial for maintaining cellular homeostasis and development. The B-cell lymphoma 2 (Bcl-2) family of proteins play a crucial role in regulating apoptosis. Overexpressed Bcl-2 proteins are associated with the development and progression of several human cancers. Annona muricata is a tropical plant that belongs to the Annonaceae family and is well known for its anticancer properties. In this study, molecular docking and simulations were performed to investigate the inhibitory potential of phytochemicals present in A...
2016: Drug Design, Development and Therapy
Gagan Deep, Rahul Kumar, Anil K Jain, Deepanshi Dhar, Gati K Panigrahi, Anowar Hussain, Chapla Agarwal, Tamam El-Elimat, Vincent P Sica, Nicholas H Oberlies, Rajesh Agarwal
Prostate cancer (PCa) is the leading malignancy among men. Importantly, this disease is mostly diagnosed at early stages offering a unique chemoprevention opportunity. Therefore, there is an urgent need to identify and target signaling molecules with higher expression/activity in prostate tumors and play critical role in PCa growth and progression. Here we report that NADPH oxidase (NOX) expression is directly associated with PCa progression in TRAMP mice, suggesting NOX as a potential chemoprevention target in controlling PCa...
March 16, 2016: Scientific Reports
Visveswaraiah Paranjyothi Magadi, Venkatadasappa Ravi, Anantharaju Arpitha, Litha, Kikkerilakshminarayana Kumaraswamy, Krishnappa Manjunath
INTRODUCTION: Malignancies constitute a wide variety of disorders having high mortality and morbidity rates. Current protocols for management include surgical intervention, chemotherapy, and radiation which possess numerous adverse effects. Many phytochemicals are available with anticancer properties similar to anticancer drugs. Major benefit of these compounds is apparent lack of toxicity to normal tissues. Graviola (botanical name: Annona Muricata) contain bioactive compound "annonaceous acetogenins" known for anticancer activity on cancer cell lines...
October 2015: Contemporary Clinical Dentistry
Chih-Chuang Liaw, Jing-Ru Liou, Tung-Ying Wu, Fang-Rong Chang, Yang-Chang Wu
In recent decades, annonaceous acetogenins have become highly studied plant secondary metabolites in terms of their isolation, structure elucidation, synthesis, biological evaluation, mechanism of action, and toxicity. The aim of the present contribution is to summarize chemical and biological reports published since 1997 on annonaceous acetogenins and synthetic acetogenin mimics. The compounds are considered biologically in terms of their cytotoxicity for cancer cell lines, neurotoxicity, pesticidal effects, and miscellaneous activities...
2016: Progress in the Chemistry of Organic Natural Products
Jun-Qiang Qian, Pei Sun, Zhan-Yu Pan, Zhi-Zhong Fang
Hepatocellular carcinoma (HCC) is the most common tumor in worldwide and chemotherapy resistant is a severe obstacle in HCC treatment. Annonaceous acetogenins was a nature compound from Uvaria accuminata and it has show the anti-tumor proliferation activity in many types cancer. In this study, we showed that annonaceous acetogenins is correlated with the drug resistance reversal in human hepatocellular carcinoma BEL-7402/5-FU and HepG2/ADM cell lines. We found that cell apoptosis was improved and cell cycle was arrested, further, multidrug-resistance proteins such as MDR1, MRP1, Topo-IIα, GST-π, cyclin D1, Survivin and bcl-2 are down-regulated, however, intracellular Rh-123 and caspase-3/8 was up-regulated by Annonaceous acetogenins treatment...
2015: International Journal of Clinical and Experimental Pathology
Y Miao, X Xu, F Yuan, Y Shi, Y Chen, J Chen, X Li
Four new annonaceous acetogenins (ACGs), squamocin-I (1), II (2) and III (3) and squamoxinone-D (4), together with seven known ACGs (5-11), were isolated from the seeds of Annona squamosa. The structures of all isolates were elucidated and characterised by spectral and chemical methods. Compounds 1-4 were evaluated for their cytotoxicities against Hep G2, SMMC 7721, BEL 7402, BGC 803 and H460 human cancer cell lines. Compound 1 exhibited better potent activity than the positive compound and compound 3 shows selectively cytotoxical activity against H460 with IC50 values of 0...
June 2016: Natural Product Research
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