Molecular mechanisms underlying anticancer effects of myricetin

Cancer is a devastating disease that has claimed many lives. Natural bioactive agents from plants are gaining wide attention for their anticancer activities. Several studies have found that natural plant-based bioactive compounds can enhance the efficacy of chemotherapy, and in some cases ameliorate some of the side-effects of drugs used as chemotherapeutic agents. In this paper, we have reviewed the literature on the anticancer effects of four plant-based bioactive compounds namely, curcumin, myricetin, geraniin and tocotrienols (T3) to provide an overview on some of the key findings that are related to this effect. The molecular mechanisms through which the active compounds may exert their anticancer properties in cell and animal-based studies also discussed.

https://www.mdpi.com/2218-273X/9/12/758/pdf

Bioactive Compounds: Natural Defense Against Cancer?

Synergy is a process in which some substances cooperate to reach a combined effect that is greater than the sum of their separate effects. It can be considered a natural “straight” strategy which has evolved by nature to obtain more efficacy at low cost. In this regard, synergistic effects may be observed in the interaction between herbal products and conventional drugs or biochemical compounds. It is important to identify and exploit these interactions since any improvement brought by such kind of process can be advantageously used to treat human disorders. Even in a complex disease such as cancer, positive synergistic plant–drug interactions should be investigated to achieve the best outcomes, including providing a greater benefit to patients or avoiding adverse side effects. This review analyzes and summarizes the current knowledge on the synergistic effects of plant–drug interactions with a focus on anticancer strategies.

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Synergistic Effects of Plant Derivatives and Conventional Chemotherapeutic Agents: An Update on the Cancer Perspective

A novel rutin-fucoidan complex based phytotherapy for cervical cancer through achieving enhanced bioavailability and cancer cell apoptosis.

Anti-tumor effects and associated molecular mechanisms of myricetin.

Drug combination therapies are common practice in the treatment of cancer. In this study, we evaluated the anticancer effects of myricetin (MYR), methyl eugenol (MEG) and cisplatin (CP) both separately as well as in combination against cervical cancer (HeLa) cells. To demonstrate whether MYR and MEG enhance the anticancer activity of CP against cervical cancer cells, we treated HeLa cells with MYR and MEG alone or in combination with cisplatin and evaluated cell growth and apoptosis using MTT (3 (4, 5 dimethyl thiazol 2yl) 2, 5 diphenyltetrazolium bromide) assay, LDH release assay, flow cytometry and fluorescence microscopy. The results revealed that, as compared to single drug treatment, the combination of MYR or MEG with CP resulted in greater effect in inhibiting cancer cell growth and inducing apoptosis. Cell apoptosis induction, Caspase-3 activity, cell cycle arrest and mitochondrial membrane potential loss were systematically studied to reveal the mechanisms of synergy between MYR, MEG and CP. Combination of MYR or MEG with CP resulted in more potent apoptosis induction as revealed by fluorescence microscopy using Hoechst 33258 and AO-ETBR staining. The combination treatment also increased the number of cells in G0/G1 phase dramatically as compared to single drug treatment. Mitochondrial membrane potential loss (ΛΨm) as well as Caspase-3 activity was much higher in combination treatment as compared to single drug treatment. Findings of this investigation suggest that MYR and MEG combined with cisplatin is a potential clinical chemotherapeutic approach in human cervical cancer.

Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines.

Objective To investigate the effect of hysteroscopy surgery combined with Mirena on postoperative adverse reactions and recurrence rate of endometrial polyps (EP). Methods A total of 312 patients who underwent hysteroscopic polypectomy of EP in our hospital from June 2017 to November 2020 were enrolled retrospectively. Among them, 42 patients did not take any treatment after the operation (control group), 156 patients were treated with levonorgestrel intrauterine birth control system (Mirena group), and 114 patients were treated with oral spironolone ethinylestradiol tablets (oral group). The clinical data of 312 patients were recorded and followed up regularly. All patients were followed up through an outpatient clinic or telephone to 12 months after the operation. The patients' age, disease course, number of pregnancies, clinical manifestations, endometrial thickness before the operation, duration of operation, amount of bleeding during the operation, and number and size of polyps were analyzed. The recurrence and postoperative side effects of EP in the three groups were followed up within 12 months after the operation. Results There was no significant difference in endometrial thickness among the three groups before treatment (P > 0.05). After 3 months, 6 months, and 12 months of treatment, the endometrial thickness of the three groups decreased, while the decrease in the Mirena group and the oral group was better compared to the control (P < 0.05). The decrease in the Mirena group was better than that in the oral group (P < 0.05). There was no significant difference in hemoglobin levels among the three groups before treatment (P > 0.05). After 3, 6, and 12 months of treatment, the hemoglobin levels of the three groups increased to varying degrees, while the levels of the Mirena group and oral group were better compared to the control (P < 0.05). Three months after the operation, the improvement of clinical symptoms was similar in the three groups, and there was no significant difference among the three groups (P > 0.05). At 6 and 12 months after the operation, the improvement of clinical symptoms in the oral group and Mirena group was better compared to the control group (P < 0.05), but there was no significant difference between the oral group and Mirena group (P > 0.05). After the operation, some patients had complications such as lower abdominal pain, breast distension pain, irregular vaginal bleeding, and abnormal liver function. There was no significant difference in the number of complications among the three groups (P > 0.05). During the follow-up to 12 months after the operation, the recurrence rate in the oral group and Mirena group was lower compared to the control (P < 0.05), and the recurrence rate in the Mirena group was lower than that in the oral group (P < 0.05). Conclusion Placing Mirena immediately after hysteroscopic polypectomy of EP can reduce the recurrence rate of endometrial polyps, increase the level of hemoglobin, and reduce the thickness of the endometrium, which can be employed and popularized according to the condition of patients in clinical work.

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Effect of Hysteroscopic Polypectomy Combined with Mirena Placement on Postoperative Adverse Reactions and Recurrence Rate of Endometrial Polyps: Based on a Large-Sample, Single-Center, Retrospective Cohort Study

This study is to investigate the pathogenesis of vulvar lichen sclerosus (VLS) by analyzing the level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low Regulatory T cells (Tregs). This study enrolled 15 VLS patients and 25 controls. Lesional and extralesional vulvar skin tissues, normal vulvar skin tissues and peripheral blood were collected. Compared with the control group, Foxp3 protein in the lesional and extralesional skin of VLS group was significantly reduced. The levels of DNMT1 and DNMT3b proteins in lesional skin of VLS group were significantly increased. There was no difference in the total methylation rates of the promoter region of the Foxp3 gene. The methylation rates of CpG1, CpG4, CpG9, and CpG10 were significantly higher in lesional skin of VLS group than in control group. There was no correlation between the total methylation rates of 10 CpG sites and the level of Foxp3 and DNMT1 proteins; there was a positive correlation between Foxp3 and DNMT1 protein in lesional skin of VLS group (r = 0.675, p < 0.05), and a negative correlation (r = -0.665, p < 0.05) in extralesional skin of VLS group. However, there was no correlation of Foxp3 with DNMT3b. The number of CD4 + CD25 + CD127low Tregs VLS decreased significantly. The expression of Foxp3 protein and the quantity of CD4 + CD25 + CD127low Tregs in patients with VLS decreased, which may cause local or systemic abnormal immunosuppression of Tregs, leading to the occurrence of VLS. This may be related with methylation or DNMT1, which needs further verification.

Jin-Ling Yi

Papers

Myricetin and methyl eugenol combination enhances the anticancer activity, cell cycle arrest and apoptosis induction of cis-platin against HeLa cervical cancer cell lines.

Effect of Hysteroscopic Polypectomy Combined with Mirena Placement on Postoperative Adverse Reactions and Recurrence Rate of Endometrial Polyps: Based on a Large-Sample, Single-Center, Retrospective Cohort Study

Level of Foxp3, DNMTs, methylation of Foxp3 promoter region, and CD4 + CD25 + CD127low regulatory T cells in vulvar lichen sclerosus