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

Effect of Aescin in Psoriatic-Induced Animal Model: Immunohistochemical and Pathological Study

Background: Aescin is a mixture of the triterpene saponins extracted from the seeds of the horse chestnut tree Aesculus hippocastanum. Aescin has a venotonic, anti-inflammatory, antioxidant and anti-edematous characteristics that are mostly connected to the agent molecular mechanism. Objective: The present study aim to investigate the potential effects of Aescin on psoriasis induced by Imiquimod in male rats, ncluding its effect on the level of tumor necrosis factor alpha, Ki-67 and the histopathologic features of the psoriatic skin. Methods: Thirty-six albino male rats were divided into six groups each group containing 6 animals, psoriasis was induced by Imiquimod to five of the groups, while for the last group vasaline was applied and the group served as a control group. The animals were then treated with topical Aescin, topical clobetasol, combination of topical Aescin and clobetasol and oral Aescin, finally all animals were sacrificed and the dorsal back skin was taken to perform histopathological and immunohistochemical analysis. Results: regarding the level of Ki-67, Strong expression of Ki-67 was seen in the group who received Imiquimod only, where the scoring of Ki-67 was notably lowered among the other groups. However, the lowest expression was noticed in the group that were treated with the combination of topical Aescin and clobetasol. While the number of TNF-α positive cells and the intensity of immunostaining were higher in the induction group who received Imiquimod only and the lowest among the group who received the combination of topical Aescin and Clobetasol. Lastly the histopathologic analysis shows that the histopathologic features of psoriasis was markedly affected by the anti-inflammatory effect of Aescin and clobetasol, which was noticed through inhibition of proinflammatory markers, and the decrease in capillary permeability. Conclusion: Topical Aescin alone or in combination with clobetasol reduced Ki-67 expression successfully; furthermore, the combination of topical Aescin and Clobetasol decreased TNF- score and had the strongest anti-inflammatory activity more than the other groups. Lastly Aescin was able to alter the histopathologic features of the psoriatic skin through its anti-inflammatory, venotonic and anti-edematous activity

Combination of Thymoquinone and Intermittent Fasting as a Treatment for Breast Cancer Implanted in Mice

Breast cancer stands out as a particularly challenging form of cancer to treat among various types. Traditional treatment methods have been longstanding approaches, yet their efficacy has diminished over time owing to heightened toxicity, adverse effects, and the emergence of multi-drug resistance. Nevertheless, a viable solution has emerged through the adoption of a complementary treatment strategy utilizing natural substances and the incorporation of intermittent fasting to enhance therapeutic outcomes. This study aimed to assess the anticancer activity of thymoquinone (TQ), intermittent fasting, and their combination using in vivo and in vitro methods. The anti-proliferative activity of TQ and fasting (glucose/serum restriction) were evaluated against the T47D, MDA-MB-231, and EMT6 cell lines and compared to normal cell lines (Vero) using the MTT colorimetric assay method. Additionally, this study aimed to determine the half-maximal inhibitory concentration (IC50) of TQ. For the in vivo experiment, the antitumor activity of TQ and intermittent fasting (IF) was assessed by measuring the tumor sizes using a digital caliper to determine the change in the tumor size and survival rates. At the molecular level, the serum levels of glucose, β-hydroxybutyrate (β-HB), leptin, and insulin growth factor-1 (IGF-1) were measured using standard kits. Additionally, the aspartate transaminase (AST), alanine transaminase (ALT), and creatinine serum levels were measured. The inhibition of the breast cancer cell lines was achieved by TQ. TQ and intermittent fasting both had an additional anticancer effect against breast tumors inoculated in mice. The combination therapy was evaluated and found to significantly reduce the tumor size, with a change in tumor size of −57.7%. Additionally, the combination of TQ and IF led to a decrease in the serum levels of glucose, IGF-1 (24.49 ng/mL) and leptin (1.77 ng/mL) while increasing β-hydroxybutyrate in the mice given combination therapy (200.86 nM) with no toxicity on the liver or kidneys. In the mice receiving combination therapy, TQ and IF treated breast cancer in an additive way without causing liver or kidney toxicity due to decreased levels of glucose, IGF-1, and leptin and increased levels of β-hydroxybutyrate. Further investigation is required to optimize the doses and determine the other possible mechanisms exhibited by the novel combination

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