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1.
Int J Mol Sci ; 24(10)2023 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-37240430

RESUMEN

Diabetes mellitus (DM) is a serious chronic metabolic disease that is associated with hyperglycemia and several complications including cardiovascular disease and chronic kidney disease. DM is caused by high levels of blood sugar in the body associated with the disruption of insulin metabolism and homeostasis. Over time, DM can induce life-threatening health problems such as blindness, heart disease, kidney damage, and stroke. Although the cure of DM has improved over the past decades, its morbidity and mortality rates remain high. Hence, new therapeutic strategies are needed to overcome the burden of this disease. One such prevention and treatment strategy that is easily accessible to diabetic patients at low cost is the use of medicinal plants, vitamins, and essential elements. The research objective of this review article is to study DM and explore its treatment modalities based on medicinal plants and vitamins. To achieve our objective, we searched scientific databases of ongoing trials in PubMed Central, Medline databases, and Google Scholar websites. We also searched databases on World Health Organization International Clinical Trials Registry Platform to collect relevant papers. Results of numerous scientific investigations revealed that phytochemicals present in medicinal plants (Allium sativum, Momordica charantia, Hibiscus sabdariffa L., and Zingiber officinale) possess anti-hypoglycemic activities and show promise for the prevention and/or control of DM. Results also revealed that intake of vitamins C, D, E, or their combination improves the health of diabetes patients by reducing blood glucose, inflammation, lipid peroxidation, and blood pressure levels. However, very limited studies have addressed the health benefits of medicinal plants and vitamins as chemo-therapeutic/preventive agents for the management of DM. This review paper aims at addressing this knowledge gap by studying DM and highlighting the biomedical significance of the most potent medicinal plants and vitamins with hypoglycemic properties that show a great potential to prevent and/or treat DM.


Asunto(s)
Diabetes Mellitus , Plantas Medicinales , Humanos , Plantas Medicinales/química , Vitaminas/uso terapéutico , Diabetes Mellitus/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Glucemia/metabolismo , Vitamina A/uso terapéutico , Vitamina K
2.
J Biomed Res Environ Sci ; 3(9): 1118-1124, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36578651

RESUMEN

Background: Prostate cancer (PCa) is one of the common cancers in males and its incidence keeps increasing globally. Approximately 81% of PCa is diagnosed during the early stage of the disease. The treatment options for prostate care include surgery, radiotherapy, and chemotherapy, but these treatments often have side effects that may lead to issues such as impotence or decreased bowel function. Our central goal is to test the apoptotic effects of Vernonia amygdalina Delile (an edible medicinal plant that is relatively inexpensive, nontoxic, and virtually without side effects) for the prevention of PCa using human adenocarcinoma (PC-3) cells as a test model. Methods: To address our central goal, PC-3 cells were treated with Vernonia amygdalina Delile (VAD). Cell cycle arrest and cell apoptosis were evaluated by Flow Cytometry assessment. Nucleosomal DNA fragmentation was detected by agarose gel electrophoresis. Results: Flow cytometry data showed that VAD induced cell cycle arrest at the G0/G1 checkpoint and significantly upregulated caspase-3 in treated cells compared to the control cells. Agarose gel electrophoresis resulted in the formation of DNA ladders in VAD-treated cells. Conclusions: These results suggest that inhibition of cancer cell growth, induction of cell cycle arrest, and apoptosis through caspase-3 activation and nucleosomal DNA fragmentation are involved in the therapeutic mechanisms of VAD as a candidate drug towards the prevention and/or treatment of PCa.

3.
Int J Mol Sci ; 23(3)2022 Jan 28.
Artículo en Inglés | MEDLINE | ID: mdl-35163459

RESUMEN

Cisplatin and other platinum-based drugs, such as carboplatin, ormaplatin, and oxaliplatin, have been widely used to treat a multitude of human cancers. However, a considerable proportion of patients often relapse due to drug resistance and/or toxicity to multiple organs including the liver, kidneys, gastrointestinal tract, and the cardiovascular, hematologic, and nervous systems. In this study, we sought to provide a comprehensive review of the current state of the science highlighting the use of cisplatin in cancer therapy, with a special emphasis on its molecular mechanisms of action, and treatment modalities including the combination therapy with natural products. Hence, we searched the literature using various scientific databases., such as MEDLINE, PubMed, Google Scholar, and relevant sources, to collect and review relevant publications on cisplatin, natural products, combination therapy, uses in cancer treatment, modes of action, and therapeutic strategies. Our search results revealed that new strategic approaches for cancer treatment, including the combination therapy of cisplatin and natural products, have been evaluated with some degree of success. Scientific evidence from both in vitro and in vivo studies demonstrates that many medicinal plants contain bioactive compounds that are promising candidates for the treatment of human diseases, and therefore represent an excellent source for drug discovery. In preclinical studies, it has been demonstrated that natural products not only enhance the therapeutic activity of cisplatin but also attenuate its chemotherapy-induced toxicity. Many experimental studies have also reported that natural products exert their therapeutic action by triggering apoptosis through modulation of mitogen-activated protein kinase (MAPK) and p53 signal transduction pathways and enhancement of cisplatin chemosensitivity. Furthermore, natural products protect against cisplatin-induced organ toxicity by modulating several gene transcription factors and inducing cell death through apoptosis and/or necrosis. In addition, formulations of cisplatin with polymeric, lipid, inorganic, and carbon-based nano-drug delivery systems have been found to delay drug release, prolong half-life, and reduce systemic toxicity while other formulations, such as nanocapsules, nanogels, and hydrogels, have been reported to enhance cell penetration, target cancer cells, and inhibit tumor progression.


Asunto(s)
Productos Biológicos/farmacología , Cisplatino/farmacología , Neoplasias/tratamiento farmacológico , Animales , Productos Biológicos/química , Productos Biológicos/uso terapéutico , Cisplatino/química , Cisplatino/uso terapéutico , Composición de Medicamentos , Sinergismo Farmacológico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Redes Reguladoras de Genes/efectos de los fármacos , Humanos
4.
J Food Nutr (Frisco) ; 7(2)2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-34395868

RESUMEN

The coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is a serious disease that has caused multiple deaths in various countries in the world. Globally, as of May 23, 2021, the total confirmed cases of COVID-19 have reach 166,346,635 with a total of 3,449,117 deaths. Several recent scientific studies have shown that medicinal plants and vitamins can benefit and improve the health of COVID-19 patients. However, the benefits of medicinal plants and vitamins in the treatment of COVID-19 remain unproven. Therefore, the objective of this article is to expounds the benefits of using medicinal plants (Allium sativum, curcumin, Nigella sativa, Zingiber officitale) and vitamins (vitamin C and vitamin D) that possess the antiviral properties for the prevention and/or control of COVID-19. To reach our objective, we searched scientific databases of ongoing trials in the Centers for Disease Control and Prevention websites, PubMed Central, Medline databases, and Google Scholar websites. We also searched databases on World Health Organization International Clinical Trials Registry Platform to collect relevant papers. We found that all of the selected medicinal plants and vitamins possess antiviral activities, and their individual intake shows promise for the prevention and/or control of COVID-19. We conclude that, the selected medicinal plants and vitamins possess anti-viral properties that are more likely to prevent and/or disrupt the SARS-CoV-2 replication cycle, enhance the human immune system and promote good health.

5.
Int J Mol Sci ; 21(12)2020 Jun 22.
Artículo en Inglés | MEDLINE | ID: mdl-32580345

RESUMEN

The treatment for ovarian cancers includes chemotherapies which use drugs such as cisplatin, paclitaxel, carboplatin, platinum, taxanes, or their combination, and other molecular target therapies. However, these current therapies are often accompanied with side effects. Vernonia calvoana (VC) is a valuable edible medicinal plant that is widespread in West Africa. In vitro data in our lab demonstrated that VC crude extract inhibits human ovarian cancer cells in a dose-dependent manner, suggesting its antitumor activity. From the VC crude extract, we have generated 10 fractions and VC fraction 7 (F7) appears to show the highest antitumor activity towards ovarian cancer cells. However, the mechanisms by which VC F7 exerts its antitumor activity in cancer cells remain largely unknown. We hypothesized that VC F7 inhibits cell proliferation and induces DNA damage and cell cycle arrest in ovarian cells through oxidative stress. To test our hypothesis, we extracted and fractionated VC leaves. The effects of VC F7 were tested in OVCAR-3 cells. Viability was assessed by the means of MTS assay. Cell morphology was analyzed by acridine orange and propidium iodide (AO/PI) dye using a fluorescent microscope. Oxidative stress biomarkers were evaluated by the means of lipid peroxidation, catalase, and glutathione peroxidase assays, respectively. The degree of DNA damage was assessed by comet assay. Cell cycle distribution was assessed by flow cytometry. Data generated from the MTS assay demonstrated that VC F7 inhibits the growth of OVCAR-3 cells in a dose-dependent manner, showing a gradual increase in the loss of viability in VC F7-treated cells. Data obtained from the AO/PI dye assessment revealed morphological alterations and exhibited characteristics such as loss of cellular membrane integrity, cell shrinkage, cell membrane damage, organelle breakdown, and detachment from the culture plate. We observed a significant increase (p < 0.05) in the levels of malondialdhyde (MDA) production in treated cells compared to the control. A gradual decrease in both catalase and glutathione peroxidase activities were observed in the treated cells compared to the control. Data obtained from the comet assay showed a significant increase (p < 0.05) in the percentages of DNA cleavage and comet tail length. The results of the flow cytometry analysis indicated VC F7 treatment caused cell cycle arrest at the S-phase checkpoint. Taken together, our results demonstrate that VC F7 exerts its anticancer activity by inhibiting cell proliferation, inducing DNA damage, and causing cell cycle arrest through oxidative stress in OVAR-3 cells. This finding suggests that VC F7 may be a potential alternative dietary agent for the prevention and/or treatment of ovarian cancer.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Vernonia/química , Apoptosis , Ciclo Celular , Proliferación Celular , Ensayo Cometa , Daño del ADN , Femenino , Humanos , Neoplasias Ováricas/patología , Células Tumorales Cultivadas
6.
Nutrients ; 11(2)2019 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-30720759

RESUMEN

Prostate cancer (PC) is one of the most common cancers in men. The global burden of this disease is rising. Its incidence and mortality rates are higher in African American (AA) men compared to white men and other ethnic groups. The treatment decisions for PC are based exclusively on histological architecture, prostate-specific antigen (PSA) levels, and local disease state. Despite advances in screening for and early detection of PC, a large percentage of men continue to be diagnosed with metastatic disease including about 20% of men affected with a high mortality rate within the African American population. As such, this population group may benefit from edible natural products that are safe with a low cost. Hence, the central goal of this article is to highlight PC disparity associated with nutritional factors and highlight chemo-preventive agents from medicinal plants that are more likely to reduce PC. To reach this central goal, we searched the PubMed Central database and the Google Scholar website for relevant papers. Our search results revealed that there are significant improvements in PC statistics among white men and other ethnic groups. However, its mortality rate remains significantly high among AA men. In addition, there are limited studies that have addressed the benefits of medicinal plants as chemo-preventive agents for PC treatment, especially among AA men. This review paper addresses this knowledge gap by discussing PC disparity associated with nutritional factors and highlighting the biomedical significance of three medicinal plants (curcumin, garlic, and Vernonia amygdalina) that show a great potential to prevent/treat PC, as well as to reduce its incidence/prevalence and mortality, improve survival rate, and reduce PC-related health disparity.


Asunto(s)
Anticarcinógenos/uso terapéutico , Negro o Afroamericano/estadística & datos numéricos , Disparidades en el Estado de Salud , Fitoterapia/métodos , Neoplasias de la Próstata/prevención & control , Adulto , Anciano , Curcumina/uso terapéutico , Ajo , Humanos , Masculino , Persona de Mediana Edad , Plantas Medicinales , Neoplasias de la Próstata/etnología , Neoplasias de la Próstata/mortalidad , Vernonia
7.
Bioact Compd Health Dis ; 2(2): 11-26, 2019 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32864583

RESUMEN

BACKGROUND: Diabetes is a metabolic pathology that affects the human body's capacity to adequately produce and use insulin. Type 1 (insulin-dependent) diabetes accounts for 5-10 % of diabetic patients. In Type 2 diabetes the insulin produced by the pancreatic islets is not properly used by cells due to insulin resistance. Gestational diabetes sometimes occurs in pregnant women and affects about 18 % of all pregnancies.Diabetes is one of the most important multifactorial metabolic chronic diseases with fatal complications. According to the International Diabetes Federation's estimations in 2015, 415 million people had diabetes and there will be an increase to 642 million people by 2040. Although many ethnopharmacological surveys have been carried out in several parts of the world, no ethnomedical and ethnopharmacological surveys have been done to identify plants used for the prevention and treatment of diabetes. OBJECTIVE: This study aimed to collect and document information on food plants' remedies consumed for the prevention and treatment of diabetes in Cameroon. METHODS: Ethnomedical and ethnopharmacological thorough preparations were conducted with 1131 interviewees from 58 tribes, following a random distribution. Diabetic patients recorded among this sample signed the informed consent and allowed us to evaluate the effectiveness of 10 identified food plants usually used for self-medication. They were divided into two groups: Group 1 comprised of 42 diabetic patients who regularly consume certain of these food plants, and Group 2 included 58 patients who were town-dwellers and did not regularly eat these identified food plants. RESULTS: It was recorded that the onset of diabetes in patients were at about 70 years and 45 years for Group 1 and Group 2 respectively. Hence, a relationship was demonstrated between the onset of diabetes and the consumption of food plants. They contributed to the prevention and/or the delay in clinical manifestations. CONCLUSION: Further investigations and/or clinical trials involving a large number of both type 1 and type 2 diabetics are needed to describe the therapeutic action of many food plants against diabetes. However, this study provides scientific support for the use of herbal medicines in the management of diabetes.

8.
Glob J Adv Eng Technol Sci ; 5(8): 1-9, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30310827

RESUMEN

The World Health Organization (WHO) has been on front line to encourage developing countries to identify medicinal plants that are safe and easily available to patients. Traditional medicine represents the first-treatment choice for the healthcare of approximately 80% of people living in developing countries. Also, its use in the United States has increased by 38% during within the last decade of the 20th century alone. Therefore, the aim of the present study was to explore the efficacy of a medicinal plant, Vernonia amygdalina Delile (VAD), as a new targeted therapy for the management of acute promyelocytic leukemia (APL), using HL-60 cells as a test model. To address our specific aim, HL-60 promyelocytic leukemia cells were treated with VAD. Live and dead cells were determined by acridine orange and propidium iodide (AO/PI) dye using the Cellometer Vision. The extent of DNA damage was evaluated by the comet assay. Cell apoptosis was evaluated by flow cytometry assessment. Data obtained from the AO/PI assay indicated that VAD significantly reduced the number of live cells in a dose-dependent manner, showing a gradual increase in the loss of viability in VAD-treated cells. We observed a significant increase in DNA damage in VAD-treated cells compared to the control group. Flow cytometry data demonstrated that VAD induced apoptosis in treated cells compared to the control cells. These results suggest that induction of cell death, DNA damage, and cell apoptosis are involved in the therapeutic efficacy of VAD. Because VAD exerts anticancer activity in vitro, it would be interesting to perform clinical trials to confirm its effectiveness as an anticancer agent towards the treatment of APL patients.

9.
Int J Eng Sci Res Technol ; 7(8): 552-556, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-30246001

RESUMEN

There is a critical need for more effective therapeutic approaches for cancer. Vernonia amygdalina Delile (VAD) has been used in African traditional medicine for the prevention and/or treatment of several diseases including diarrhea, intestinal illnesses, and cancer. However, the effects of VAD on human lung cancer and human prostate cancer cells remain largely unknown. The aim of this study was to explore a novel cellular staining protocol using acridine orange/propidium iodide (AO/PI) and to test the antiproferative activity of VAD against human lung cancer (A-549) cells and human prostate cancer (PC-3) cells. Our studies demonstrate that VAD inhibits the proliferation of both A-549 and PC-3 cells in a dose-dependent manner. This finding suggests that VAD may be useful in lung and prostate cancer prevention. However, further research is needed to elucidate the chemopreventive effects of VAD against cancer.

10.
J Anal Pharm Res ; 4(4)2017.
Artículo en Inglés | MEDLINE | ID: mdl-29098206

RESUMEN

In many developing countries traditional medicine constitutes a major part of health care because of its local availability and affordability compared to modern medicine. However, little is known about the specific uses and availability of medicinal plants. In this research an exploratory study was conducted to determine the uses of three medicinal plants in Cameroon, and to examine their relative distribution and abundance in specific habitats. From a questionnaire administered to traditional healers, we and found that three species of medicinal plants including: Alstonia boonei, Picralima nitida and Sarcocephalus latifolius that are commonly used, either singly or in mixtures to treat human diseases such as muscle and joints pains, hyperthermia, hypertension, hepatitis, jaundice and rheumatism. Fresh or dry barks of the tree plants and fresh fruits of Picralima nitida, as well as various ethnopharmacological preparations (decoctions, maceration, infusion and powder) are widely commercialized. Findings from our ecological study revealed that Alstonia boonei was represented by 2, or 1 % of total individuals recorded in 0.5 ha, implying 3 individuals and 6 trees/ha. This tree was well represented and was sometime among the forests. Picralima nitida was represented by 0.6 % of total trees recorded in 0.5 ha, implying 0.70 tree and 1 tree/ha. This tree was poorly represented and was not a dominant species in its habitats. Sarcocephalus latifolius belonged to a group of 72 plants with a recovery < 5% corresponding to Braun- Blanquet scale1. Hence, this plant was not densely represented in the Sudono-Guinean and Sahelian savannahs. It is the most harvested species of the three species that has undergone a strong anthropogenic destruction. Therefore these three plants, and especially Sarcocephalus latifolius, need to be protected through a sustainable management of their habitats in Cameroon.

11.
Pharm Anal Acta ; 8(1)2017.
Artículo en Inglés | MEDLINE | ID: mdl-29057143

RESUMEN

OBJECTIVE: High blood pressure is a public health challenge worldwide. According to World Health Organization, 30% of men and 50% of women 65 to 75 years old are suffering from high blood pressure. The number of hypertensive patients in the world will attain 1.56 billion of people, with 60% increase in prevalence. The incidence of high blood pressure increases with age, but nowadays, is being noticed an increasing incidence in young people. The socio-cultural medicine may provide new solutions in the management of this pathology. Therefore this study was carried out to record and document plants used against high blood pressure in socio-cultural medicine for future drugs discovery worldwide. METHODS: An ethno botanical survey was realized between 2002 and 2016 to identify manifold plants used to fight against high blood pressure. This survey was carried out in three phytogeographic regions of Cameroon. Amongst people living in those regions, 1131 randomly screened interviewees distributed in 58 socio-cultural groups were involved in this study. RESULTS: This survey reveals that about 70% of interviewees don't know high blood pressure which is a symptomless disease. A total of 28 species of plants were recorded. These plants belong to 25 genera and 24 families. They were used to prepare 28 herbal remedies for the treatment of high blood pressure. In the morphological point of view about 10/28 (36%) plants are herbs; 9/28 (32%) plants are trees and 9/28 (32%) plants are shrubs. Only 3/28 plants (11%) used including Allium sativum, Aloe barteri and Aloe buttneri) are cultivated. This means that the plants used in this study don't usually have some form of protection through cultivation which is encouraging in terms of their conservation. CONCLUSION: The uncontrolled use of a hypotensive plants can provoke a fatal hypotension in hypertensive patients. Therefore the use of hypotensive plants needs to be controlled by physician or by a patient verification using a blood pressure monitor. Recorded species which will slow the high blood pressure will be used for the preparation of phytodrugs.

12.
Molecules ; 22(10)2017 Sep 22.
Artículo en Inglés | MEDLINE | ID: mdl-28937624

RESUMEN

Prostate cancer patients have been suffering from limited treatment options due to late diagnosis, poor drug tolerance, and multi-drug resistance to almost all the current drug treatments. Therefore, it is important to seek a new alternative therapeutic medicine that can effectively prevent the disease and even eradicate the progression and metastasis of prostate cancer. Vernonia amygdalina Delile (VAD) is a common edible vegetable in Cameroon that has been used as a traditional medicine for some human diseases. However, to the best of our knowledge, no previous reports have explored its therapeutic efficacy against human prostate cancer. The objective of the present study was to assess the anticancer activities of VAD methanolic extracts in the prevention and treatment of prostate cancer using human androgen-independent prostate cancer (PC-3) cells as a test model. To achieve our objective, PC-3 cells were treated with various doses of VAD for 48 h. Data generated from the trypan blue test and MTT assay demonstrated that VAD extracts exhibited significant growth-inhibitory effects on PC-3 cells. Collectively, we established for the first time the antiproliferative effects of VAD on PC-3 cells, with an IC50 value of about 196.6 µg/mL. Further experiments, including cell morphology, lipid peroxidation and comet assays, and apoptosis analysis showed that VAD caused growth-inhibitory effects on PC-3 cells through the induction of cell growth arrest, DNA damage, apoptosis, and necrosis in vitro and may provide protection from oxidative stress diseases as a result of its high antioxidant content. These results provide useful data on the anticancer activities of VAD for prostate cancer and demonstrate the novel possibilities of this medicinal plant for developing prostate cancer therapies.


Asunto(s)
Extractos Vegetales/química , Extractos Vegetales/farmacología , Neoplasias de la Próstata/metabolismo , Vernonia/química , Antioxidantes/química , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Humanos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Medicina Tradicional , Estrés Oxidativo/efectos de los fármacos , Hojas de la Planta/química
13.
Artículo en Inglés | MEDLINE | ID: mdl-26550582

RESUMEN

A majority of Africans rely on traditional medicine as the primary form of health care. Yet most traditional medicine products have a short shelf life, especially for water-based formulations such as macerations, infusions and decoctions. Indeed, many of these water extracts become unfit for human consumption after five to seven days of conservation either because of the degradation or toxicity of active components, and/or the growth of pathogenic organisms. The purpose of this study was to describe and apply a new approach for the development of an improved traditional medicine (ITM) that is cheap, very efficient, not toxic, and easy to produce, and that can be conserved for a longer time without a significant loss of activity. Hence, Laportea ovalifolia was selected from an ethnobotanical prospection in all regions of Cameroon, and was used to prepare an oral hypoglycemic product. This preparation required 9 steps focused on the characterization of the plant species, and the standardization of the ethnopharmacological preparation by a multidisciplinary team of scientists with expertise in botany, ecology, pharmacognosy and pharmacology. Resultantly, four galenic formulations of hypoglycemic medications were produced. A relationship between these four formulations was described as follow: One spoon of oral suspension (10 ml)=one sachet of powder=2 tablets=3 capsules. Hence, our research provides new insight into a drug discovery approach that could alleviate the major problems affecting traditional medicine and enhance its effectiveness in addressing health care in developing and undeveloped countries.

14.
J Cancer Sci Ther ; 2012(Suppl 3): 6, 2012 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-23847719

RESUMEN

INTRODUCTION: Garlic supplementation in diet has been shown to be beneficial to cancer patients. Recently, its pharmacological role in the prevention and treatment of cancer has received increasing attention. However, the mechanisms by which garlic extract (GE) induces cytotoxicity, oxidative stress, and apoptosis in cancer cells remain largely unknown. OBJECTIVE: The present study was designed to use HL-60 cells as a test model to evaluate whether or not GE-induced cytotoxicty and apoptosis in human leukemia (HL-60) cells is mediated through oxidative stress. METHODS: Human leukemia (HL-60) cells were treated with different concentrations of GE for 12 hr. Cell survival was determined by MTT assay. The extent of oxidative cell/tissue damage was determined by measuring malondialdehyde (lipid peroxidation biomarker) concentrations by spectrophotometry. Cell apoptosis was measured by flow cytometry assessment (Annexin-V and caspase-3 assays) and agarose gel electrophoresis (DNA laddering assay). RESULTS: Data obtained from the MTT assay indicated that GE significantly (p < 0.05) reduced the viability of HL-60 cells in a concentration-dependent manner. We detected a significant (p < 0.05) increase in malondialdehyde (MDA) concentrations in GE-treated HL-60 cells compared to the control. Flow cytometry data showed a strong concentration-response relationship between GE exposure and Annexin-V positive HL-60 cells. Similarly, a statistically significant and concentration-dependent increase (p <0.05) were recorded with regard to caspase-3 activity in HL-60 cells undergoing late apoptosis. These results were confirmed by data of DNA laddering assay showing a clear evidence of nucleosomal DNA fragmentation in GE-treated cells. CONCLUSION: Our finding indicates that GE-induced cytotoxicity and apoptosis in HL-60 cells involve phosphatidylserine externalization, caspase-3 activation, and nucleosomal DNA fragmentation associated with the formation of MDA, a by-product of lipid peroxidation and biomarker of oxidative stress. At therapeutic concentrations, GE-induced cytotoxic and apoptotic effects in HL-60 cells is mediated by oxidative stress.

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