56 research outputs found
Antiproliferative Activity of Plant Extracts Used Against Cancer in Traditional Medicine
Forty four extracts from sixteen plants used traditionally as anticancer agents were evaluated in vitro for their antiproliferative activity against Hep-2, MCF-7, and Vero cell lines. Plants were fractionated using ethanol, methanol, chloroform, n-hexane, distilled water, and butanol. The antiproliferative activity was measured by MTT assay. TLC was used to identify active fractions. The apoptotic activity of active fractions was determined using TUNEL colorimetric assay. 20 of these extracts demonstrated significant antiproliferative activity against one or more of the cell lines. These extracts were prepared from Ononis hirta, Inula viscosa, Salvia pinardi, Verbascum sinaiticum and Ononis sicula. Methanol fractions of Ononis hirta (aerial parts) and Inula viscosa (flowers) were the most active fractions against MCF-7 cells with IC50 of 27.96 and 15.78 μg/ml respectively and they were less toxic against other cell lines. Other extracts showed lower activity against cancer cell lines. TLC analysis showed the presence of flavonoids and terpenoids in active plants while alkaloids were detected in Ononis hirta (aerial parts) extracts. Ononis hirta (aerial parts) and Inula viscosa (flowers) extracts exerted their antiproliferative activity by inducing apoptosis in cancer cell lines. Further studies are necessary for detailed chemical characterization and more extensive biological evaluation of the most active ingredients
Targeting cisplatin resistance in breast cancer using a combination of Thymoquinone and Silymarin: an in vitro and in vivo study
Background: Breast cancer (BC) is considered the most diagnosed cancer among women globally. This is because of its high possibility of metastasis and high resistance to chemotherapy. Cisplatin is a platinum-based antitumor agent that is used to treat various types of cancer. However, the main obstacle to using this drug is drug resistance. Drug resistance is a cause of most relapses of cancer which eventually lead to death. Nowadays, combining natural products is a trend to overcome drug resistance. Thymoquinone (TQ) is a natural phytochemical that exists mainly in blackseed. It has been used in medicine for decades, especially as an anticancer agent. Silymarin is a milk thistle compound that exhibits anticancer, hepatoprotective, and neuroprotective activity. Hence, the combination of TQ and silymarin could be a probable solution to treat cancer and reduce chemoresistance. Methods: This study tested this combination on cisplatin-sensitive (EMT6/P) and cisplatin-resistant (EMT6/CPR) mouse mammary cell lines. Apoptotic and antiproliferative activity was assessed for TQ and silymarin in vitro using caspase-3 and [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] (MTT) assays, respectively. An in vivo study was performed to evaluate the effect of TQ and silymarin combination in mice inoculated with EMT6/P and EMT6/CPR cells. The safety profile was also examined using creatinine and liver enzyme assays. Results: In vitro, the TQ and silymarin combination synergized in both cell lines. Also, this combination caused apoptosis induction at a higher rate than the single treatment in both cell lines. In vivo, TQ and silymarin combination resulted in a remarkable reduction in tumor size and enhanced the cure rate in mice implanted with EMT6/P and EMT6/CPR cell lines. According to the safety profile results, TQ and silymarin combination was safe. Conclusion: In conclusion, the combination of TQ and silymarin provides a promising solution in treating BC resistant to cisplatin by inducing apoptosis. Further studies are needed to define the exact anticancer mechanisms of this combination
Immunomodulatory and anticancer activities of hyacinthus orientalis l.: An in vitro and in vivo study
Hyacinthus orientalis L. (family Hyacinthaceae) is traditionally used to treat different diseases including cancer. In this study, the anticancer and immunomodulatory effects of this plant were evaluated. Hydroalcoholic extract was prepared, and different solvent fractions were obtained using solvent–solvent extraction. In the anticancer part, MTT assay and caspase-3 ELISA kits were used to measure the antiproliferative and apoptosis induction ability for each extract, respectively. In the immunomodulatory part, lymphocyte proliferation assay and cytokines detection kit were used to measure the effect of extracts of acquired immunity. Phagocytosis and pinocytosis induction were used to evaluate the effect of extracts on the innate immunity. GC–MS, LC–MS, and Foline–Ciocalteu assays were used to identify the chemical composition of the plant. Balb/C mice were inoculated with breast cancer and treated with hydroalcoholic extract of H. orientalis L. Results showed that hydroalcoholic extract and n-hexane fraction were highly effective in apoptosis induction. Both extract and fraction were also effective in stimulating lymphocytes proliferation and phagocytosis. Significant reduction in tumor size was achieved after treating tumor-bearing mice with hydroalcoholic extract. Additionally, high cure percentages (50%) were obtained in treated mice. Results of this study showed that H. orientalis L. has promising anticancer and immunomodulatory activities. However, further studies are needed to explore more details of apoptosis induction ability and other mechanisms of action and to measure different signaling pathways responsible for the anticancer and immunomodulatory response
Resveratrol and tumor microenvironment: mechanistic basis and therapeutic targets
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Resveratrol (3,40,5 trihydroxystilbene) is a naturally occurring non-flavonoid polyphenol. It has various pharmacological effects including antioxidant, anti-diabetic, anti-inflammatory and anti-cancer. Many studies have given special attention to different aspects of resveratrol anti-cancer properties and proved its high efficiency in targeting multiple cancer hallmarks. Tumor microenvironment has a critical role in cancer development and progression. Tumor cells coordinate with a cast of normal cells to aid the malignant behavior of cancer. Many cancer supporting players were detected in tumor microenvironment. These players include blood and lymphatic vessels, infiltrating immune cells, stromal fibroblasts and the extracellular matrix. Targeting tumor microenvironment components is a promising strategy in cancer therapy. Resveratrol with its diverse biological activities has the capacity to target tumor microenvironment by manipulating the function of many components surrounding cancer cells. This review summarizes the targets of resveratrol in tumor microenvironment and the mechanisms involved in this targeting. Studies discussed in this review will participate in building a solid ground for researchers to have more insight into the mechanism of action of resveratrol in tumor microenvironment
Xanthium spinosum L. Extracts Inhibit Breast Cancer in Mice by Apoptosis Induction and Immune System Modulation
Plants have been considered for many years as an important source of medicine to treat different diseases. Xanthium spinosum L. (Asteraceae, Compositae) is known for its diuretic, anti-inflammatory, and sedative effects. It is also used in the treatment of several ailments, such as cancer. In order to evaluate the anticancer and immunomodulatory activities, crude ethanol extract was prepared from the aerial part of X. spinosum and then fractionated using solvents with different polarities. As well, the chemical composition of X. spinosum extract and fractions were identified using LC-MS analysis. The antitumor effect of X. spinosum was assessed in both in vitro and in vivo models. Apoptosis induction was measured in vitro using a caspase-3 activity kit. Lymphocyte proliferation and phagocytosis and pinocytosis induction were used to quantify the effect of the plant extract and fractions on acquired and innate immunity, respectively. The effect of X. spinosum extract, and fractions on the levels of cytokines (IFN-γ, IL-2, IL-4, and IL-10) in murine lymphocytes was determined using a mouse-uncoated TH1/TH2 ELISA kit. Results showed that ethanol extract had the highest antiproliferative activity (IC₅₀ = 2.5 mg mL−1) against EMT6/P cell lines, while the aqueous and chloroform fractions had the highest apoptotic activity with 2.2 and 1.7 folds, respectively. On the other hand, the n-hexane fraction was the most effective in stimulating lymphocyte proliferation, whereas ethanol extract, aq. Methanol and aqueous fractions exhibited the highest phagocytic activity. As well, X. spinosum extract and fractions were able to modulate the expression of IL-2, IL-4, and IFN-γ. A remarkable decrease in tumor size was accomplished following the treatment of tumor-bearing mice with X. spinosum extract and fractions. Both aq. Methanol and chloroform fractions showed the highest percentage change in tumor size with -58 and -55%, respectively. As well, tumor-bearing mice treated with chloroform fraction demonstrated a high curable percentage with a value of 57.1%. Anyway, X. spinosum extract and fractions exhibited no toxic impact on the liver or kidney functions of the mice-treated groups. These findings may confirm that X. spinosum has favorable anticancer and immunomodulatory effects. However, additional studies are required to fully understand the mechanisms of action of this plant and the signaling pathways involved in its effects. Moreover, more testing is needed to have better insight into the apoptotic pathway and to know the exact concentration of active compounds
Study of the antitumor activity of the combination baicalin and epigallocatechin gallate in a murine model of vincristine-resistant breast cancer
Background: Breast cancer is one of the primary causes of death in women worldwide. Yearly, a quarter of cancer cases in women are breast cancer. The problem is aggravated by the emergence of chemotherapeutic resistance. One of the practices to overcome this problem is using natural products along with chemotherapy. Epigallocatechin Gallate (EGCG) is the main efficient catechin in green tea. Baicalin is the main active chemical constituent of Scutellaria baicalensis. Both natural products have anti-cancer and improving resistance activities. Therefore, a combination of EGCG and baicalin may afford a possible way out to overcome chemotherapeutic resistance. Methods: EGCG and baicalin were tested on Vincristine-sensitive (EMT-6/P) and Vincristine-resistant (EMT-6/V) mouse mammary cell lines. Antiproliferative and apoptotic effects were assessed for EGCG, baicalin, their combination, and Vincristine in vitro using MTT and caspase-3 assays. An in vivo study was conducted to assess the effect of EGCG, baicalin, their combination, vincristine, vincristine along with the combination in both EMT-6/P and EMT-6/V mouse mammary cell lines. The safety profile was also considered using liver enzymes and creatinine assays. Results: in vitro, EGCG and baicalin had synergistic effects in both cell lines. The combination of baicalin and EGCG as 140 and 100 µM respectively, caused an apoptotic effect higher than the single treatment of baicalin 175 µM or EGCG 125 µM, in vincristine-resistant cell lines. In vivo, the combination along with vincristine significantly enhanced the reduction of tumour size in mice implanted with EMT-6/P and EMT-6/V cell lines. According to the safety profile, the combinations of EGCG and baicalin are safe. Conclusion: The combination of baicalin and EGCG can be optimistic in improving vincristine-resistant cells to treatments
Role of vitamins A, C, D, E in cancer prevention and therapy: therapeutic potentials and mechanisms of action
Cancer, a leading global cause of mortality, arises from intricate interactions between genetic and environmental factors, fueling uncontrolled cell growth. Amidst existing treatment limitations, vitamins have emerged as promising candidates for cancer prevention and treatment. This review focuses on Vitamins A, C, E, and D because of their protective activity against various types of cancer. They are essential as human metabolic coenzymes. Through a critical exploration of preclinical and clinical studies via PubMed and Google Scholar, the impact of these vitamins on cancer therapy was analyzed, unraveling their complicated mechanisms of action. Interestingly, vitamins impact immune function, antioxidant defense, inflammation, and epigenetic regulation, potentially enhancing outcomes by influencing cell behavior and countering stress and DNA damage. Encouraging clinical trial results have been observed; however, further well-controlled studies are imperative to validate their effectiveness, determine optimal dosages, and formulate comprehensive cancer prevention and treatment strategies. Personalized supplementation strategies, informed by medical expertise, are pivotal for optimal outcomes in both clinical and preclinical contexts. Nevertheless, conclusive evidence regarding the efficacy of vitamins in cancer prevention and treatment is still pending, urging further research and exploration in this compelling area of study
Terfezia boudieri: A Desert Truffle With Anticancer and Immunomodulatory Activities
© Copyright © 2020 Al Obaydi, Hamed, Al Kury and Talib. Desert truffles have high nutritional value and grow wild in the Mediterranean basin and Western Asia. Although, many studies were performed to evaluate truffles nutritious values and phytochemical composition, studies are limited to evaluate their anticancer and/ or immunomodulatory effects. Our study was conducted to evaluate the anticancer and immunomodulatory effects of Terfezia boudieri (desert truffle). Different solvent extracts were prepared from the truffle and MTT assay was used to measure their anticancer activity against cancer cell lines (T47D, MCF-7, MDA-MB231, HCT-116, and Hela). Total phenolic content in each extract was determined by using Folin-Ciocalteu reagent and qualitative phytochemical screening was performed using standard methods. The degree of apoptosis induction (using caspase 3 assay) and vascular endothelial growth factor expression were detected using standard kits. Also, ELISA was used to measure levels of IFN-γ, IL-2, IL-4, and IL-10 secreted by splenocytes after treatment with the extracts. The effect of the extracts on splenocytes proliferation was measured using MTT assay. Macrophage function was evaluated using nitro blue tetrazolium assay and pinocytosis function was evaluated using neutral red method. Terpenoids, phytosterols, and carbohydrates were present in all the solvent extracts, while tannins, alkaloids and flavonoids were detected only in aqueous/methanol and aqueous extracts. The highest total phenolic content was observed in aqueous and aqueous methanol extracts. The growth of cancer cell lines was inhibited by T. boudieri extracts in a dose dependent manner. N-hexane extract was the most potent against most cell lines. Aqueous/methanol extract showed high apoptosis induction and angiogenesis suppression effects. An increase in TH1 cytokines (IFN-γ, IL-2) level and a decrease in TH2 cytokine (IL-4) level were evident after lymphocytes stimulation by aqueous/methanol, n-hexane and ethyl acetate extracts of T. boudieri. Ethyl acetate extract of T. boudieri were the most potent extracts to stimulate lymphocytes proliferation while all other extracts showed moderate stimulation. Aqueous/methanol extract was the most active extract to stimulate phagocytosis. Ethyl acetate extract was the most active extract to stimulate pinocytosis. The use of T. boudieri provides variable health benefits. N-hexane, ethyl acetate, and aqueous/methanol extracts exhibited anticancer activities and are potent stimulators of innate and acquired immunity. Further testing is needed to identify the biologically active compounds and detect them quantitatively using GC-MS analysis
New derivatives of sulfonylhydrazone as potential antitumor agents: Design, synthesis and cheminformatics evaluation
Phosphoinositide 3-kinase α (PI3Kα) is a propitious target for designing anticancer drugs. A series of new N\u27-(diphenylmethylene)benzenesulfonohydrazide was synthesized and characterized using FT-IR, NMR (1H and 13C), HRMS, and elemental analysis. Target compounds exhibited an antiproliferative effect against the human colon carcinoma (HCT-116) cell line. Our cheminformatics analysis indicated that the para-tailored derivatives [p-NO2 (3) and p-CF3 (7)] have better ionization potentials based on calculated Moran autocorrelations and ionization potentials. Subsequent in vitro cell proliferation assays validated our cheminformatics results by providing experimental evidence that both derivatives 3 and 7 exhibited improved antiproliferative activities against HCT-116. Hence, our results emphasized the importance of electron-withdrawing groups and hydrogen bond-acceptors in the rational design of small-molecule chemical ligands targeting PI3Kα. These results agreed with the induced-fit docking against PI3Kα, highlighting the role of p-substituted aromatic rings in guiding the ligand-PI3Kα complex formation, by targeting a hydrophobic pocket in the ligand-binding site and forming π-stacking interactions with a nearby tryptophan residue
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