Complementary Drug Research Articles

Resveratrol (RV): A pharmacological review and call for further research

Resveratrol (RV) is a well-known polyphenolic compound in various plants, including grape, peanut, and berry fruits, which is quite famous for its association with several health benefits such as anti-obesity, cardioprotective neuroprotective, antitumor, antidiabetic, antioxidants, anti-age effects, and glucose metabolism. Significantly, promising therapeutic properties have been reported in various cancer, neurodegeneration, and atherosclerosis and are regulated by several synergistic pathways that control oxidative stress, cell death, and inflammation. Similarly, RV possesses a strong anti-adipogenic effect by inhibiting fat accumulation processes and activating oxidative and lipolytic pathways, exhibiting their cardioprotective effects by inhibiting platelet aggregation. The RV also shows significant antibacterial effects against various food-borne pathogens (Listeria, Campylobacter, Staphylococcus aureus, and E. coli) by inhibiting an electron transport chain (ETC) and F0F1-ATPase, which decreases the production of cellular energy that leads to the spread of pathogens. After collecting and analyzing scientific literature, it may be concluded that RV is well tolerated and favorably affects cardiovascular, neurological, and diabetic disorders. As such, it is possible that RV can be considered the best nutritional additive and a complementary drug, especially a therapeutic candidate. Therefore, this review would increase knowledge about the blend of RV as well as inspire researchers around the world to consider RV as a pharmaceutical drug to combat future health crises against various inhumane diseases. In the future, this article will be aware of discoveries about the potential of this promising natural compound as the best nutraceuticals and therapeutic drugs in medicine.

Comparison of Intranasal Steroid Application Using Nasal Saline Irrigation and a Mucosal Atomization Device to Treat Chronic Rhinosinusitis.

Introduction: Chronic rhinosinusitis (CRS) is a disease that can significantly reduce patients' quality of life (QoL). Intranasal steroid therapy is the most commonly used treatment for CRS. There are many evaluation tools dedicated to assessing CRS patients' QoL, but none of them evaluates QoL during local steroid therapy. Mucosal atomization devices (MADs) and nasal saline irrigation (NSI) are effective and safe methods of applying intranasal steroids for CRS patients. Materials and Methods: The sample population for this prospective study comprised 43 CRS patients. Following endoscopic sinus surgery, all participants received intranasal steroids administered via an MAD, followed by NSI for 1.5 months. Each participant completed the SNOT-22 (22-item Sino-Nasal Outcomes Test) score and a new questionnaire, the Complementary Topical Nasal Drug Delivery Questionnaire (the Complementary Questionnaire), at the end of 3 months of intranasal steroid therapy. Results: The patients' responses in both the SNOT-22 score and the Complementary Questionnaire revealed significant differences in their adverse experiences. The patients who received intranasal steroid treatment using NSI experienced more frequently delayed nasal drainage, higher frequency of ear symptoms, and facial pain/pressure, while those whose therapy was administered using an MAD reported complaints such as nasal irritation, nasal dryness, and postnasal drip with unpleasant taste/smell. Conclusion: We used the Complementary Questionnaire as an effective tool for assessment of the QoL of CRS patients. The SNOT-22 score and the Complementary Questionnaire make it possible to select an intranasal applicator tailored to a CRS patient's specific complaints.

COVID-19 vaccines and treatments: When speed is necessary and not enough.

COVID-19 vaccines and treatments: When speed is necessary and not enough.

A standardized extract of Ziziphus jujuba Mill protects against adriamycin-induced liver, heart, and brain toxicity: An oxidative stress and biochemical approach.

Due to the antioxidant effects of the Ziziphus jujuba Mill (Z. jujuba), we investigated the liver, heart, and brain-protective effects of this herb against toxicity induced by adriamycin (ADR). In this study, Wistar rats were divided into 1) control, 2) ADR and 3, 4, and 5) treated groups orally administrated three doses of Z. jujuba hydroalcoholic extract for 1month. The liver, heart, and brain were removed for evaluation of the oxidative markers. Blood samples were evaluated to determine the levels of Lactate dehydrogenase, total and direct bilirubin, alkaline phosphatase, Aspartate transaminase, and Alanine aminotransferase. Administration of Z. jujuba significantly decreased the biochemical enzymes compared to the ADR. Oxidative condition in treated rats with different doses of Z. jujuba was improved compared to the ADR group. Z. jujuba could decrease the oxidative injury through invigoration of the tissues antioxidant system. The mentioned hepatic and cardiac parameters levels improved during extract administration. PRACTICAL APPLICATIONS: In the first stage, our findings and other supplementary works have shown that administration of jujube extract has prevented the effects of histotoxicity caused by adriamycin, so it seems that in the next stage, the effects of this herbal plant on patients with tissue toxicity caused by adriamycin should be evaluated and if the results are positive in pharmacological studies, it should be used as a complementary drug in the treatment of these patients.

Potential inhibitors interacting in Neuropilin-1 to develop an adjuvant drug against COVID-19, by molecular docking

The COVID-19 pandemic continues without specific treatment. In this study it is proposed compounds that can be developed as adjuvant / complementary drugs against COVID-19. Through a search for molecular docking, for the development of a new drug using pharmacological compounds targeting the b1 region in neuropilin-1 (NRP1), which is important for the interaction with the S1 region of the S-Protein of SARS-CoV-2, to slow down the infection process of this virus.A molecular docking was performed using almost 500,000 compounds targeted to interact in the region between amino acids (Thr316, Asp320, Ser346, Thr349, and Tyr353) in NRP1 to determine compounds able to hinder the interaction with the S1 region in the S-Protein.In this study, ten compounds are proposed as potential inhibitors between S1 region in the S-Protein of SARS-CoV-2 with the b1 region in NRP1, to develop a new adjuvant / complementary drug against COVID-19, and to hinder the interaction between SARS-CoV-2 and human cells, with a high probability to be safe in humans, validated by web servers for prediction of ADME and toxicity (PreADMET).

Transcriptome analysis evinces anti-neoplastic mechanisms of hypericin: A study on U87 glioblastoma cell line

AimsHypericin (HYP) from Hypericum perforatum has cytotoxic effects on a variety of malignant cell types, but the pattern of gene expression mediating the effect is largely unknown. Here we sought to analyze the response of U87 glioblastoma (GBM) cell lines in response to HYP. Materials and methodsU87 cell line was treated by HYP. Cytotoxicity was assessed using MTT and Annexin V/PI assays. Gene expression profile was obtained using high-throughput sequencing. Enrichment analysis was performed on differentially expressed genes (DEGs). Upstream transcription factors and microRNAs regulating DEGs were predicted. The effects of DEGs on survival of GBM patients were calculated. Protein-protein interaction analysis was conducted to obtain key altered genes. The possible effect of HYP treatment on immunity response was evaluated. Key findingsThe IC50 of HYP on U87 cell line was determined to be 1.5 μg/ml. The main type of cell death was apoptosis. A total of 312 DEGs were found. Affected Gene Ontology terms and pathways were identified. Analysis of upstream modulators of DEGs pointed out to transcription factors that significantly overlap with GBM stem cell transcription factor. Survival analysis suggested that HYP works best for the mesenchymal subtype patients. Tumor infiltration analysis predicted that HYP may affect Treg and macrophage infiltration in vivo. Using expression pattern of GBM patients and HYP-induced DEGs we suggested Fedratinib as a complementary drug to HYP. SignificanceOur study represents the response of U87 cell line to HYP, with analyses on survival, transcription factors and personalization according to GBM subtype.

Comment on ‘Clopidogrel can be an effective complementary prophylactic for drug-refractory migraine with patent foramen ovale’

Dear Editor, Migraine puts a considerable burden on societies with a prevalence of about 14.4% globally.1 It is reported that patent foramen ovale (PFO) is associated with migraine, and its...

AphaMax®, an Aphanizomenon Flos-Aquae Aqueous Extract, Exerts Intestinal Protective Effects in Experimental Colitis in Rats.

Background: Aphanizomenon flos-aquae (AFA) is a unicellular cyanobacterium considered to be a “superfood” for its complete nutritional profile and beneficial properties. We investigated possible beneficial effects of an AFA extract, commercialized as AphaMax®, containing concentrated amount of phycocyanins and phytochrome, in 2,4 dinitrobenzensulfonic acid(DNBS)-induced colitis in rats. Methods: Effects of preventive oral treatment of AphaMax® (20, 50 or 100 mg/kg/day) in colitic rats were assessed and then macroscopic and microscopic analyses were performed to evaluate the inflammation degree. Myeloperoxidase (MPO) activity and NF-κB, pro-inflammatory citockines, cycloxygenase-2 (COX-2), and inducible NOS (iNOS) levels of expression were determined, as Reactive Oxygen Species (ROS) and nitrite levels. Results: AphaMax® treatment attenuated the severity of colitis ameliorating clinical signs. AphaMax® reduced the histological colonic damage and decreased MPO activity, NF-κB activation, as well as iNOS and COX-2 expression. AphaMax® treatment improved the altered immune response associated with colonic inflammation reducing IL-1β, IL-6 expression. Lastly, AphaMax® reduced oxidative stress, decreasing ROS and nitrite levels. Conclusions: Preventive treatment with AphaMax® attenuates the severity of the inflammation in DNBS colitis rats involving decrease of the NF-kB activation, reduction of iNOS and COX-2 expression, and inhibition of oxidative stress. Due its anti-inflammatory and antioxidant proprieties AphaMax® could be a good candidate as a complementary drug in inflammatory bowel disease (IBD) treatment.

Experimental studies of boron neutron capture therapy (BNCT) using histone deacetylase inhibitor (HDACI) sodium butyrate, as a complementary drug for the treatment of poorly differentiated thyroid cancer (PDTC)

PurposeThe present study analyzed different protocols of administration of boronophenylalanine (BPA) and sodium butyrate (NaB) to increase the BNCT efficacy for poorly differentiated thyroid cancer (PDTC). Materials and methodsNude mice implanted with human PDTC cells (WRO) were distributed into four protocols: 1) BPA; 2) BPA + ip NaB; 3) BPA + oral NaB; 4) Control. Biodistribution and histologic studies were performed. LAT (BPA transporter) isoforms gene expression was assessed by RT-PCR. ResultsTumor growth delay was observed in animals of the Protocol #3 (p < 0.05). NaB (Protocol #2) increased tumor boron uptake 2-h post BPA injection (p < 0.05). On the other hand, NaB upregulated the expression of all the isoforms of the LAT transporter in vitro. Histologic studies showed a significant decrease of mitotic activity and an increase of vacuoles in tumors of Protocol #3. Neutrons alone or combined with NaB caused some tumor growth delay (p < 0.05), while in the BNCT and BNCT + NaB groups, there was a halt in tumor growth in 70 and 80% of the animals, respectively. ConclusionsIntraperitoneally administration of NaB increased boron uptake while oral administration for a longer period of time induced tumor growth delay previous to BPA administration. The use of NaB via ip would optimize the irradiation results.

ASSESSMENT OF PATIENT-CARE, FACILITY CARE, AND COMPLEMENTARY DRUG USE INDICATORS AMONG ELDERLY PATIENTS IN A TERTIARY CARE HOSPITAL OF WESTERN NEPAL

Objective: The current study aims to determine the pattern of drug usage in terms of patient-care, facility care, and complementary drug use indicators among elderly people.&#x0D; Methods: The study was a prospective cross-sectional study that was conducted in the outpatient department. Patient-care, facility care, and complementary drug use indicators were assed as per the WHO/INRUD indicators. Patient/patient party knowledge of correct dose was analyzed by the information; time of administration (when) and quantity of drugs to be taken (how much).&#x0D; Results: The duration of consultation in the ophthalmology department was comparatively longer (30.33 min) than in other departments. The dispensing time of the medicine department was 126.60 s which was higher than other departments. Among the total medicines, 88.58% were dispensed, 21 (1.06%) of the total drugs had the patient’s name labeled on the envelope while 1430 (81.53%) of the drugs had drug name and 1617 (92.19%) only had the administration time labeled on the envelope. On interviewing patients/patient parties, 240 (59.55%) knew both the time of administration and the number of drugs to be taken. The average medicine cost encountered per patient was found to be Nepalese rupees (NRs.) 1353±1079 NRs. (US$ 11.57±9.23).&#x0D; Conclusion: It is concluded that systematic changes need to be applied to improve the patient knowledge, to deliver quality advice to the patients, and to maintain the process of adequate labeling in medications.

Arthrocen, an avocado‐soy unsaponifiable agent, improves acetic acid‐induced colitis in rat by inhibition of NF‐kB signaling pathway

The goal of the current study was to evaluate the anti-inflammatory effect of Arthrocen against acetic acid-induced colitis in rats. Acute inflammation was produced through intrarectal administration of 2ml diluted acetic acid (4%) solution. All interventions were carried out for 5days after colitis induction. Arthrocen was administered orally at doses of 30, 60, and 120mgkg-1 day-1 . Then, macroscopic and microscopic studies were performed. Myeloperoxidase (MPO) activity and tumor necrosis factor-α (TNF-α) activity were measured by biochemical and ELISA methods, respectively. Immunohistochemistry was done to investigate the expression of pNF-κB. The results of this study demonstrated that Arthrocen reduced macroscopic and microscopic damage compared to the acetic acid group. Furthermore, Arthrocen decreased the activity of MPO and TNF-α as well as the protein expression of pNF-kB in rat colon tissue. The results of the current study revealed the anti-inflammatory activity of Arthrocen in acetic acid mediated colon inflammation through suppressing the NF-κB pathway. PRACTICAL APPLICATIONS: Inflammatory bowel disease (IBD) is an immune-mediated chronic relapsing disorder affecting the gastrointestinal tract (GIT) characterized by chronic bowel inflammation. A plant-based dietary supplement containing avocado and soy unsaponifiable extracts in a ratio of 1:2 is known as Arthrocen. Arthrocen can be used as a complementary drug beside current drugs in clinical trials for the treatment of IBD.

Management of heart failure and type 2 diabetes mellitus: Maximizing complementary drug therapy.

Type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular disease and occurs in ~25% of patients with heart failure (HF). Patients with co-morbid HF and T2DM are at elevated risk of adverse outcomes, making optimization of complementary drug therapies essential. While research is ongoing, recent advances in drug therapy, including the introduction of sacubitril/valsartan for HF with reduced ejection fraction and the finding of positive cardiovascular effects of glucose-lowering agents (particularly sodium-glucose co-transporter-2 [SGLT2] inhibitors) have the potential to transform pharmacologic management of co-morbid HF and T2DM. In this review, we provide a comprehensive overview of cardiovascular clinical trials of therapies for HF and diabetes mellitus to date and identify areas requiring further investigation. We also discuss the pathophysiologic overlap of the two diseases and explore the complementary therapeutic effects of HF and T2DM drugs, with a particular focus on sacubitril/valsartan and SGLT2 inhibitors.

Jianpi Huayu Decoction Attenuates the Immunosuppressive Status of H22 Hepatocellular Carcinoma-Bearing Mice: By Targeting Myeloid-Derived Suppressor Cells

Tumor-induced immunosuppressive microenvironment in which myeloid-derived suppressor cells (MDSCs) plays an important role, remains an obstacle for effective oncotherapy currently. Inducing MDSCs into maturation was confirmed as an effective method to reduce the tumor-bearing host's immunosuppression. Traditional Chinese medicines (TCM) possess characteristics of alleviating immunosuppression of cancer patients and low toxicity. Jianpi Huayu Decoction (JHD) was an experienced formula of TCM for oncotherapy based on TCM theory and clinical practice. We previously observed that JHD attenuated the expression of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β) in tumor. IL-10 and TGF-β were found to be cytokines positively related to immunosuppression induced by MDSCs. Here, our study was designed to further investigate the regulation of JHD on the immune system in the H22 liver-cancer mouse model. Mainly, flow cytometry was used to detect the proportion of immune cells, to analyze the apoptosis, differentiation and reactive oxygen species of MDSCs. We found that JHD significantly reduced the destruction of spleen structure, reduced the proportion of regulatory T cells (Treg) and T helper 17 cells (Th17), and increased the proportion of cytotoxic T lymphotes (CTL), Dendritic cells (DC) and CD11b+Gr-1+cells in spleen, but with no significant change of T helper 1 cells (Th1), T helper 2 cells (Th2) and macrophages. In vitro experiments showed that apoptosis of MDSCs was decreased as the time of JHD stimulation increased, which partly explained the increase of CD11b+Gr-1+cells in the spleen. Meanwhile, JHD could promote the differentiation of MDSCs into macrophages and dendritic cells, attenuate expression of ROS in MDSCs and reduce its inhibition on the proliferation of CD4+ T cells, in vitro. Therefore, that the proportion of CD11b+Gr-1+ cells increased in the spleen of tumor-bearing hosts may not be villainy after treatment, when these drugs suppress the immunosuppressive ability of CD11b+Gr-1+ cells and promote it mature to replenish dendritic cell, at the same time. Generally, JHD may be a complementary and alternative drug for attenuating the immunosuppressive status induced by hepatocellular carcinoma, possibly by promoting differentiation and inhibiting the immunosuppressive activity of MDSCs.

Rational Combination Therapy for Melanoma with Dinaciclib by Targeting BAK-Dependent Cell Death.

Mutation of the oncogene BRAF is among the most common genetic alterations in melanoma. BRAF inhibitors alone or in combination with MEK inhibitors fail to eradicate the tumor in most patients due to combinations of intrinsic or acquired resistance. Therefore, novel strategies are needed to improve the therapeutic efficacy of BRAF inhibition. We demonstrated that dinaciclib has potent antimelanoma effects by inducing BAK-dependent apoptosis through MCL1 reduction. Contrary to dinaciclib, the inhibitors of BRAF/MEK/CDK4/6 induced apoptosis dominantly through a BAX-dependent mechanism. Although the combination of BRAF and MEK inhibitors did not exhibit additive antimelanoma effects, their combination with dinaciclib synergistically inhibited melanoma growth both in vitro and in vivo Collectively, our present findings suggest dinaciclib to be an effective complementary drug of BAX-dependent antimelanoma drugs by targeting BAK-mediated apoptosis, and other such rational drug combinations can be determined by identifying complementary drugs activating either BAK or BAX.

Evaluation of antidiabetic activity of Pleurotus pulmonarius against streptozotocin-nicotinamide induced diabetic wistar albino rats.

The current research aims to evaluate the antidiabetic properties of Pleurotus pulmonarius, an edible basidiomycetes mushroom fungi in diabetic induced wistar albino rats. Mycelial Hot Water Extracts (HWE) and Acetone Extracts (AE) of Pleurotus pulmonarius was orally administrated to STZ-NA induced (55 mg/kilogram body weight) diabetic wistar albino rats at a concentration of 200 and 400 mg/kg for 4 weeks. The outcomes revealed that the HWE of Pleurotus pulmonarius resulted in a significant (p < 0.001) reduction in blood glucose level. A noteworthy (p < 0.001) reduction in serum lipid profile and elevation in High-Density Lipoprotein Cholesterol (HDL-C) after administration with HWE, also demonstrating the protective effects of HWE in diabetes-related complications. Besides all antidiabetic parameters, pathological morphology of the pancreas, liver and kidney are regularised. This observation indicated that HWE of Pleurotus pulmonarius possessed higher antidiabetic activity than AE. Besides, HWE also promoted a significant control of alpha amylase enzyme in a concentration-dependent manner with a maximum activity of 99.23% inhibition at 1000 µg/ml. The outcomes of the present study indicated that the HWE possesses a potential antidiabetic activity both in vitro and in vivo. Thus, it can be used as a nontoxic complementary drug in the controlling of diabetes and related complications, thus providing scientific authentication of its use as an antidiabetic agent.

Anticancer evaluation of N-benzoyl-3-allylthiourea as potential antibreast cancer agent through enhances HER-2 expression.

Breast cancer with HER-2 overexpression is sensitive to drugs which target the receptor or its kinase activity. Although the anti-HER-2 therapies commonly used have improved patient outcome, resistance usually occurs. In this present study, we investigated a modification of the chemical structure of allylthiourea derivatives in order to enhance the cytotoxicity effect on breast cancer cells with HER-2 overexpression. The aim of this research was to predict the absorption, distribution, metabolism, excretion, and toxicity by in silico study and to explore the effect N-benzoyl-3-allylthiourea (BATU) on MCF-7 cell line with overexpressing of HER-2 using MTT assay and western blot. The result showed that the cytotoxicity effects of BATU on MCF-7/HER-2 cell line (IC50 value 0.64 mM) were higher than on MCF-7 cell lines (IC50 value 1.47 mM). In addition, the cytotoxic effects of BATU on MCF-7 and MCF-7/HER-2 were higher than allylthiourea as a lead compound (IC50 value 5.22 and 3.17 mM). The results also confirmed that the BATU compound has the ability to effectively enhance its cytotoxicity against MCF-7/HER-2 through enhanced HER-2 expression and inhibition of nuclear factor kappa B (NF-kB) activation. Above all, the BATU compound is effective in increasing HER-2 expression and inactivating NF-kB transcription factors, thereby resulting in inhibition of protein expression which works a significant part in cell proliferation. Therefore, the BATU compound has the potential to be developed as a complementary drug in breast cancer therapy with HER-2 positive.

The return of the megamerger

After a year in which deals were few and far between, major drug firms made up for lost time in 2019. This year, big pharma companies brought back the megamerger, inking several mammoth deals that will reconfigure the industry ranks. They also made a slew of midsize purchases meant to add technology or bolster a key therapeutic portfolio. According to an analysis done by the investment firm SVB Leerink, global pharmaceutical merger and acquisition activity is on track to hit a 10-year peak in 2019. Leerink expects total transaction value for the year to reach or exceed $250 billion. Bristol-Myers Squibb kicked off the bustling year by announcing it would pay $74 billion to acquire Celgene in a deal designed to create a leader in cancer and immunology, areas where the companies have complementary drug portfolios. That deal led to another sizable one: in August, Celgene agreed to sell its

Protein Encapsulation of Experimental Anticancer Agents 5F 203 and Phortress: Towards Precision Drug Delivery.

IntroductionAdvancement of novel anticancer drugs into clinical use is frequently halted by their lack of solubility, reduced stability under physiological conditions, and non-specific uptake by normal tissues, causing systemic toxicity. Their progress to use in the clinic could be accelerated by the development of new formulations employing suitable and complementary drug delivery vehicles.MethodsA robust method for apoferritin (AFt)-encapsulation of antitumour benzothiazoles has been developed for enhanced activity against and drug delivery to benzothiazole-sensitive cancers.ResultsMore than 70 molecules of benzothiazole 5F 203 were encapsulated per AFt cage. Post-encapsulation, the size and integrity of the protein cages were retained as evidenced by dynamic light scattering. ToF-SIMS depth profiling using an argon cluster beam confirmed 5F 203 exclusively within the AFt cavity. Improved encapsulation of benzothiazole lysyl-amide prodrugs was achieved (~130 molecules of Phortress per AFt cage). Transferrin receptor 1, TfR1, was detected in lysates prepared from most cancer cell lines studied, contributing to enhanced anticancer potency of the AFt-encapsulated benzothiazoles (5F 203, Phortress, GW 610, GW 608-Lys). Nanomolar activity was demonstrated by AFt-formulations in breast, ovarian, renal and gastric carcinoma cell lines, whereas GI50 >50 µM was observed in non-tumourigenic MRC-5 fibroblasts. Intracellular 5F 203, a potent aryl hydrocarbon receptor (AhR) ligand, and inducible expression of cytochrome P450 (CYP) 1A1 were detected following exposure of sensitive cells to AFt-5F 203, confirming that the activity of benzothiazoles was not compromised following encapsulation.ConclusionOur results show enhanced potency and selectivity of AFt-encapsulated 5F 203 against carcinomas derived from breast, ovarian, renal, colorectal as well as gastric cancer models, and offer realistic prospects for potential refinement of tumour-targeting and treatment, and merit further in vivo investigations.

Arsenic Sulfide Nanoformulation Induces Megakaryocytic Differentiation through Histone Deacetylase Inhibition

AbstractArsenic sulfide (As4S4) is a mineral drug that can be administrated orally and has been applied in several Chinese medicine formulations for the treatment on some kinds of myeloid leukemia. However, mechanisms of As4S4 are not demonstrated adequately due to the poor water solubility of As4S4 in its original crystal form. The authors previously fabricated water dissolvable arsenic sulfide nanoformulation (ee‐As4S4), which downregulated intracellular reactive oxygen species (ROS). As ROS is closely associated with the histone deacetylase (HDAC), in this study the effect of ee‐As4S4 on the HDAC activity in chronic myeloid leukemia (CML) cells and whether the effect can induce subsequent megakaryocytic differentiation and underlying mechanisms are investigated. Results show that ee‐As4S4 inhibits HDAC activity in CML cells, resulting in the suppression of cellular respiration. The inhibition of HDAC activity also leads to the transcriptional activation of RUNX1, which induces megakaryocytic differentiation in CML cell lines, evidenced by the significantly multiple nuclei and giant nuclear structure, upregulation of CD41a and the increased phosphorylation of ERK1/2. In conclusion, ee‐As4S4 is able to inhibit HDAC activity, and therefore induce significant megakaryocytic differentiation in CML cells through RUNX1‐dependent pathways, which suggests its clinical potential as a complementary drug option for CML patients.

Sodium Selenite Accentuates the Therapeutic Effect of Adriamycin Prodrug (PADM) against Gastric Cancer.

Selenium has remained a controversial character in cancer research. While its antitumor effects have been widely demonstrated, further evidence is required to establish it as a robust treatment regime. Sodium selenite (SS), an inorganic selenium, reportedly affected the proliferation and redifferentiation of gastric cancer cells, but whether it could act as a complement to conventional chemotherapeutic drugs for combination therapy is uncertain. Herein, SGC-7901 and MGC-803 gastric cancer cells were treated with PADM (Ac-Phe-Lys-PABC-ADM), a prodrug of doxorubicin/adriamycin (ADM), and the combined antitumor effects of the two drugs were evaluated. Characterization after treatment revealed that although PADM exhibited antitumor effects individually by inhibiting the proliferation and migration of gastric cancer cells and inducing apoptosis, the addition of SS significantly amplified these effects. Furthermore, gastric cancer cell apoptosis triggered by the combined treatment of SS and PADM may involve the participation of mitochondrial apoptosis, as evidenced by the changes in mitochondrial morphology and occurrence of mitochondrial fission. Collectively, SS could be a strong complementary drug that accentuates the therapeutic potential of PADM in gastric cancer treatment and management, and its significance could contribute to unique and innovative anticancer strategies.