Alternative Cancer Treatment Research Articles

Antitumoral activity of homeopathic and anthroposophic Viscum album's preparations: an in vitro assay

Background: Viscum album (mistletoe) has been used for a variety of purposes and is widely used as an alternative treatment for cancer and other diseases. Preparations of fermented extracts from Viscum album (VA), a plant from the Loranthaceae family, have been used, mainly in European countries, with promising results as adjuvant therapies, especially in Anthroposophic Medicine.1,2,3. In vitro studies have demonstrated that various types of VA may have cytotoxic activity in carcinoma cells, being able to activate the apoptotic cascade or leading cells to necrosis. It is possible to prepare VA extracts using different procedures and solvents. The homeopathic preparations involve the use of ethanol as solvent4, while the antroposophic preparations are obtained in aqueous solvent5. 
 Aims: The present study aimed to verify the cytotoxic effects of homeopathic and anthroposophic Viscum album preparations in human leukaemic K562 cell line. 
 Methodology: The cytotoxic effects of anthroposophic (ISCADOR A - IA; ISCADOR P - IP; ISCADOR M - IM; ISCADOR U - IU; ISCADOR Qu - IQu) and homeopathic Viscum album extracts (VA) were evaluated in K562 cells. For this, ten independent experiments of Trypan blue assay and five independent MTT assay were carried out.6 Additionally, cell morphology was analysed by phase inverted contrast microscopy coupled to digital camera (Optika XDS-3).7 The results were expressed as mean±SD, and statistical comparisons were performed by one-way ANOVA. 
 Results: All samples tested were able to interfere with viability and mitochondrial activity, with important morphological damage, when compared to respective controls. Considering the ISCADOR samples all of them presented similar cytotoxic activity, with lower activity attribute to IP (around 25% of viable cells) in comparison to 90% of non-viable cells induced by other samples. The homeopathic preparation originated the best results compared to anthroposophic samples. Morphological analyses supported the MTT and trypan blue assays´ results. 
 Conclusion: The anticancer activity tested in K562 indicate that all Viscum album samples have anticancer activity, in a dose dependent manner. Further tests need to be done in order to contribute for the understanding of the Viscum album antitumoral mechanisms, as well as about differences between homeopathic and antroposophic procedures.

Berberine Shows Proapoptotic Effect and Potentiation of Cytotoxic Drugs Acitivity in Colorectal Adenocarcinoma Cells

Colorectal cancer, despite advances in treatment and diagnosis, is one of the most common causes of death from cancer. Conventional anticancer treatment is associated with serious side effects, therefore, new strategies are needed to reduce its toxicity. Natural compound berberine has shown antiproliferative activity against various cancer cells including colon. To investigate antiproliferative effect of berberine in human colorectal adenocarcinoma cells and its ability to potentiate the effect of convenient cytostatics taxol, docetaxel, doxorubicin and cisplatin we used MTT assay and flow cytometry was used to detect its proapoptotic effect and effect on cell cycle. In our experiments we observed significant antiproliferative activity of berberine chloride with IC50= 6.7526 μM. Combination of berberine chloride (1μM) with taxol, docetaxel, doxorubicin and carboplatin significantly increased their antiproliferative activity and decreased their IC50 values. Cell cycle analysis revealed increase in sub-G0 /G1 fraction considered as apoptotic and very mild increase in G0/G1 fraction in berberine chloride (5μM) treated cells. proapoptotic effect of berberine chloride (5μM) was confirmed by Annexin V/PI staining. Based on our results, we can assume that berberine has antiproliferative effect and the combination of berberine with cytostatics could be a promising alternative treatment for cancer. Further studies are necesary to investigate the exact mechanisms of action and drug – drug interactions.

A potential bat adenovirus-based oncolytic virus targeting canine cancers

Although a canine adenovirus (CAdV)-based oncolytic virus (OV) candidate targeting canine tumors has been reported, its oncolytic effect could be attenuated by CAdV vaccine-induced neutralizing antibodies in dog patients. To circumvent this issue, we focused on the bat adenovirus (BtAdV) strain, which was previously isolated from healthy microbats. We previously showed that this virus replicated efficiently in canine cell lines and did not serologically cross-react with CAdVs, suggesting that it may offer the possibility of an OV candidate for canine tumors. Here, we tested the growth properties and cytotoxicity of the BtAdV Mm32 strain in a panel of canine tumor cells and found that its characteristics were equivalent to those of CAdVs. To produce an Mm32 construct with enhanced tumor specificity, we established a novel reverse genetics system for BtAdV based on bacterial artificial chromosomes, and generated a recombinant virus, Mm32-E1Ap + cTERTp, by inserting a tumor-specific canine telomerase reverse transcriptase promoter into its E1A regulatory region. The growth and cytotoxicity of this recombinant were superior to those of wild-type Mm32 in canine tumor cells, unlike in normal canine cells. These data suggest that Mm32-E1Ap + cTERTp could be a promising OV for alternative canine cancer therapies.

Cesium Treatment Depresses Glycolysis Pathway in HeLa Cell.

Cesium (Cs) is an alkali metal element that is of no essential use for humans; it has no known beneficial function that is verified by clinical research. When used as an alternative cancer therapy, it even causes toxicity in high doses. Thus, before using Cs as treatment in clinical settings, it is important to clearly determine its biological effects on cells. However, Cs was found to suppress the proliferation of human cervical cancer cells in a dose-dependent manner, and it was assumed that Cs inhibits the glycolysis pathway. In this study, we clearly determined the step of the glycolysis pathway that is affected by Cs. The glycolytic enzyme expressions, activities, and metabolite concentrations in HeLa cells were measured by PCR, western blotting, and enzymatic methods, after treating the cells with Cs for 3 days. Cs treatment decreased transcriptional and expression levels of hexokinase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate kinase (PK), and lactate dehydrogenase and the activity of PK. Analysis of glycolysis pathway metabolites revealed that Cs treatment reduces lactate level and increases the level of nicotinamide adenine dinucleotide (oxidized form, NAD+); however, it did not affect the levels of pyruvate and nicotinamide adenine dinucleotide (reduced form, NADH). Increase of the [NAD+]/[NADH] ratio and decrease of the [lactate]/[pyruvate] ratio indicate that Cs treatment inhibits the aerobic glycolysis pathway. Cs treatment inhibits PK activity and increases the [NAD+]/[NADH] ratio. Hence, Cs has been determined to inhibit glycolysis, especially the aerobic glycolysis pathway. These results suggest that suppression of HeLa cell proliferation following Cs treatment was caused by inhibition of aerobic glycolysis by Cs.

Sonodynamic therapy and common head and neck cancers: in vitro and in vivo studies.

Carcinogenesis is a complex multi-stage process associated with abnormal oncogenic signals in various signaling pathways. HNSCC (Head and neck squamous cell carcinoma) includes the majority of head and neck cancers (HNC). Also, HNSCC indicates a tumors heterogeneous group that derives from the squamous epithelium of the oropharynx, hypopharynx, oral cavity, and larynx. The main cancer management approach contains chemotherapy, radiation, and surgery separately or in combination. Each therapeutic approach has a limitation that influences cancer therapy procedures. Different treatment manners, stimuli-responsive therapeutic methods can improve on-target responses and reduce side effects. Sonodynamic therapy (ST) shows promising potential as an alternative treatment for cancer in the last few years. There is a hypothesis that shows ST using sonosenitizer in combination with low-intensity ultrasound (LIUS) could be useful in all kinds of cancer without focusing on specific target proteins, molecules, and/or genes. This review study discussed the application of ST for the treatment, ST mechanisms, and also, advances in the treatment of HNCs approaches in the recent decades.

Anticancer activity of RAPTA-EA1 in triple-negative BRCA1 proficient breast cancer cells: single and combined treatment with the PARP inhibitor olaparib

RAPTA-EA1 is a promising glutathione transferase (GSTP-1) inhibitor that has previously been shown to inhibit the growth of various breast cancer cells. We studied the anticancer activity of RAPTA-EA1 on triple-negative BRCA1 competent breast cancer MDA-MB-231 cells. MDA-MB-231 cells are significantly more sensitive to RAPTA-EA1 than MCF-7 cells. Treatment reveals a higher degree of cytotoxicity than cisplatin against both cell lines. Ruthenium accumulation in MDA-MB-231 cells is mainly in the nuclear fraction (43%), followed by the cytoplasm (30%), and the mitochondria (27%). RAPTA-EA1 blocks cell growth at the G2/M phase, leading to nuclear condensation and cell death. The compound slightly inhibits DNA replication of the 3,426-bp fragment of the BRCA1 exon 11 of the cells, with approximately 0.6 lesion per the BRCA1 fragment. The expression of BRCA1 mRNA and its protein in the Ru-treated cells is curtailed by 50–80% compared to the untreated controls. Growth inhibition of the triple-negative BRCA1 wild-type MDA-MB-231 and the sporadic BRCA1 wild-type MCF-7 cells by olaparib (a poly [ADP-ribose] polymerase (PARP) inhibitor) is dose-dependent, with MDA-MB-231 cells being two-fold less susceptible to the drug than MCF-7 cells. Combining olaparib with RAPTA-EA1 results in a combination index (CI) of 0.78 (almost additive) in MDA-MB-231 cells and 0.24 (potent synergy) in the MCF-7 cells. The PARP inhibitor alone differently regulates the expression of BRCA1 mRNA in both cell lines, whereas the olaparib-RAPTA-EA1 combination induces overexpression of BRCA1 mRNA in these cells. However, the expression level of the BRCA1 protein is dramatically reduced after treatment with the combined inhibitors, compared with the untreated controls. This observation highlights the cellular responses of triple-negative BRCA1 proficient breast cancer MDA-MB-231 cells to RAPTA-EA1 through BRCA1 inhibition and provides insights into alternative treatments for breast cancer.

Modulation of Temoporfin Distribution in Blood by β-Cyclodextrin Nanoshuttles.

Photodynamic therapy represents a more targeted and less invasive alternative cancer treatment to traditional modalities. Temoporfin, as with many photosensitizers, is given by injection into a vein, and its subsequent fate is largely determined by the binding to plasma proteins and interaction with endothelial and blood cells. Thus, it is essential to be able to control and to alter the biodistribution of temoporfin in blood. In the present study, we evaluated the effect of co-administration of temoporfin with randomly methylated β-CD (Me-β-CD) on the distribution of temoporfin in the main subpopulations of blood cells of healthy donors using absorbance spectrophotometry and flow cytometry. We showed that cell-bound temoporfin fraction in blood strongly depends on the concentration of Me-β-CD. In fact, the accumulation of temoporfin in white blood cells was more sensitive than that in red blood cells, due to the higher volume of membranous organelles in white blood cells. Finally, we demonstrated that Me-β-CD significantly increases cellular uptake of temoporfin cancer human Burkitt′s lymphoma Raji cells. The presence of Me-β-CD resulted in a spotted pattern of temoporfin distribution in the plasma membrane compartment. Our results clearly demonstrated that β-CDs derivatives provide new options to modulate temoporfin biodistribution in blood.

Hypoxia-responsive nanoreactors based on self-enhanced photodynamic sensitization and triggered ferroptosis for cancer synergistic therapy

BackgroundPhotodynamic therapy (PDT), a typical reactive oxygen species (ROS)-dependent treatment with high controllability, has emerged as an alternative cancer therapy modality but its therapeutic efficacy is still unsatisfactory due to the limited light penetration and constant oxygen consumption. With the development of another ROS-dependent paradigm ferroptosis, several efforts have been made to conquer the poor efficacy by combining these two approaches; however the biocompatibility, tumor-targeting capacity and clinical translation prospect of current studies still exist great concerns. Herein, a novel hypoxia-responsive nanoreactor BCFe@SRF with sorafenib (SRF) loaded inside, constructed by covalently connecting chlorin e6 conjugated bovine serum albumin (BSA-Ce6) and ferritin through azobenzene (Azo) linker, were prepared to offer unmatched opportunities for high-efficient PDT and ferroptosis synergistic therapy.ResultsThe designed BCFe@SRF exhibited appropriate size distribution, stable dispersity, excellent ROS generation property, controllable drug release capacity, tumor accumulation ability, and outstanding biocompatibility. Importantly, the BCFe@SRF could be degraded under hypoxia environment to release BSA-Ce6 for laser-triggered PDT, ferritin for iron-catalyzed Fenton reaction and SRF for tumor antioxidative defense disruption. Meanwhile, besides PDT effects, it was found that BCFe@SRF mediated treatment upon laser irradiation in hypoxic environment not only could accelerate lipid peroxidation (LPO) generation but also could deplete intracellular glutathione (GSH) and decrease glutathione peroxidase (GPX4) expression, which was believed as three symbolic events during ferroptosis. All in all, the BCFe@SRF nanoreactor, employing multiple cascaded pathways to promote intracellular ROS accumulation, presented remarkably outstanding antitumor effects both in vitro and in vivo.ConclusionBCFe@SRF could serve as a promising candidate for synergistic PDT and ferroptosis therapy, which is applicable to boost oxidative damage within tumor site and will be informative to future design of ROS-dependent therapeutic nanoplatforms.Graphic abstract

Anti-Cancer Potential of Nggorang Leaves Extract (Salvia Occidentalis SW.) as a Protein P53 Supressor in T47D Cells

Breast cancer is one of the most common types of cancer in women. The high incidence of breast cancer has led to the development of anticancer drugs that are more selective against cancer cells without damaging normal tissues. One of the alternatives in cancer treatment by looking for natural sources that can be developed, Nggorang leaves (Salvia occidentalis Sw.). This plant is found in Tenda Village, Langke Rembong District, Manggarai Regency, NTT Province, when the leaves are harvested for one year and are used as medicine. As a preventive, this leaf has been used for generations as an anticancer (7 leaves boiled with 200 ml of water to 100 ml and then drunk), for wounded breast cancer (crushed leaves and attached to the wound); stamina enhancer, cough, influenza, hemorrhoids, diarrhea, nosebleeds (Primary data, 2014). This study aims to prove the potential of EDG (Nggorang Leaves Extract) as an antiproliferative against Hela cancer cells and protein P53 suppressor. The method used is the Quasy experiment, because this study uses laboratory tests in sample testing. The results of the cytotoxic test of Nggorang Leaves Extract have the potential to be anti-proliferative against cancer cells T47D IC50 at 201 ppm and Nggorang Leaves Extract (EDG) has the potential to increase p53 gene suppression in T47D cancer cells by 94.13% at a concentration of 50 ppm.

Neoadjuvant chemoteraphy in unresectable ovarian cancer with olaparib and weekly carboplatin plus paclitaxel: a phase II, open label multicenter study (NUVOLA trial)

BackgroundNeoadjuvant chemotherapy with interval debulking surgery represents an alternative treatment for advanced ovarian cancer. Currently, there are few data about the use of poly adenosine diphosphate-ribose polymerase inhibitors in the...

Theoretical Study on Specific Loss Power and Heating Temperature in CoFe2O4 Nanoparticles as Possible Candidate for Alternative Cancer Therapy by Superparamagnetic Hyperthemia

In this paper, we present a theoretical study on the maximum specific loss power in the admissible biological limit (PsM)l for CoFe2O4 ferrimagnetic nanoparticles, as a possible candidate in alternative and non-invasive cancer therapy by superparamagnetic hyperthermia. The heating time of the nanoparticles (Δto) at the optimum temperature of approx. 43 °C for the efficient destruction of tumor cells in a short period of time, was also studied. We found the maximum specific loss power PsM (as a result of superparamegnetic relaxation in CoFe2O4 nanoparticles) for very small diameters of the nanoparticles (Do), situated in the range of 5.88–6.67 nm, and with the limit frequencies (fl) in the very wide range of values of 83–1000 kHz, respectively. Additionally, the optimal heating temperature (To) of 43 °C was obtained for a very wide range of values of the magnetic field H, of 5–60 kA/m, and the corresponding optimal heating times (Δto) were found in very short time intervals in the range of ~0.3–44 s, depending on the volume packing fraction (ε) of the nanoparticles. The obtained results, as well as the very wide range of values for the amplitude H and the frequency f of the external alternating magnetic field for which superparamagnetic hyperthermia can be obtained, which are great practical benefits in the case of hyperthermia, demonstrate that CoFe2O4 nanoparticles can be successfully used in the therapy of cancer by superaparamagnetic hyperthermia. In addition, the very small size of magnetic nanoparticles (only a few nm) will lead to two major benefits in cancer therapy via superparamagnetic hyperthermia, namely: (i) the possibility of intracellular therapy which is much more effective due to the ability to destroy tumor cells from within and (ii) the reduced cell toxicity.

Advances in neoadjuvant therapy for resectable pancreatic cancer over the past two decades.

In the last two decades, pancreatic cancer has been undergoing important changes in its perioperative management due to the great interest in multidisciplinary management and preoperative multimodal therapy, which in numerous studies have shown promising clinical results. Although the standard of treatment for resectable pancreatic ductal adenocarcinoma (PDAC) today is surgery followed by adjuvant therapy, as it is a biologically aggressive disease, even with complete resection, it has high rates of local and distant relapse. Several retrospective and prospective phase I/II studies have opened the window for neoadjuvant therapy with chemotherapy (CT), chemoradiotherapy (CRT), or both, as an alternative treatment for resectable pancreatic cancer, with promising results. Neoadjuvant therapy could has some advantages, including early administration of systemic treatment, in vivo assessment of response to treatment, increase resectability rate in borderline patients, increase resection rate with negative margin and survival benefit. While it seems clear that even potentially resectable disease would benefit from preoperative multimodal therapy, the optimal neoadjuvant therapeutic strategy is still controversial and currently there are only recommendations for neoadjuvant treatment, in clinical guidelines such as the NCCN and ESMO, for borderline and/or locally advanced PDAC. This review provides an overview of recent studies available and how they relate to systemic treatment of resectable PDAC in the neoadjuvant setting.

Chinese Propolis Suppressed Pancreatic Cancer Panc-1 Cells Proliferation and Migration via Hippo-YAP Pathway.

Pancreatic cancer is one of the most malignant cancers with high mortality. Therefore, it is of great urgency to develop new agents that could improve the prognosis of Pancreatic cancer patients. Chinese propolis (CP), a flavonoid-rich beehive product, has been reported to have an anticancer effect. In this study, we applied CP to the human Pancreatic cancer cell line Panc-1 to verify its impact on tumor development. CP induced apoptosis in Panc-1 cells from 12.5 µg/mL in a time- and dose-dependent manner with an IC50 value of approximately 50 µg/mL. Apoptosis rate induced by CP was examined by Annexing FITC/PI assay. We found that 48 h treatment with 50 µg/mL CP resulted in 34.25 ± 3.81% apoptotic cells, as compared to 9.13 ± 1.76% in the control group. We further discovered that the Panc-1 cells tended to be arrested at G2/M phase after CP treatment, which is considered to contribute to the anti-proliferation effect of CP. Furthermore, our results demonstrated that CP suppressed Panc-1 cell migration by regulating epithelial–mesenchymal transition (EMT). Interestingly, the Hippo pathway was activated in Panc-1 cells after CP treatment, serving as a mechanism for the anti-pancreatic cancer effect of CP. These findings provide a possibility of beehive products as an alternative treatment for pancreatic cancer.

Cell surface heat shock protein-mediated entry of tumor cell-adapted rotavirus into U-937 cells.

Rotaviruses infect cells by binding to specific cell surface molecules including gangliosides, heat shock protein cognate protein 70 (Hsc70), and some integrins. The characterization of cell surface receptors defining viral tropism is crucial for inhibiting entry into the normal cells or the cancer cells. In the present work, several tumor cell-adapted rotavirus isolates were tested for their interaction with some heat shock proteins (HSPs) present in the U-937 cells, derived from a human pleural effusion (histiocytic lymphoma monocyte). This interaction was examined by virus overlay protein-binding (VOPB), immunochemistry, immuno-dot blot assays, and flow cytometry. The results indicated that the rotavirus isolates studied were able to infect U937 cells by interacting with Hsp90, Hsp70, Hsp60, Hsp40, Hsc70, protein disulfide isomerase (PDI), and integrin β3, which are implicated in cellular proliferation, differentiation, and cancer development. Interestingly, these cellular proteins were found to be associated in lipid microdomains (rafts), facilitating in this way eventual sequential interactions of the rotavirus particles with the cell surface receptors. The rotavirus tropism for U937 cells through the use of these cell surface proteins made this rotavirus isolates an attractive target for the development of oncolytic strategies in the context of alternative and complementary treatment of cancer.

Novel Single Inhibitor of HDAC6/8 and Dual Inhibitor of PI3K/HDAC6 as Potential Alternative Treatments for Prostate Cancer.

Background: Prostate cancer is the second most frequently diagnosed malignancy worldwide. Here, the cytotoxic and antimetastatic effects of a new HDAC6/8 inhibitor, LASSBio-1911, and a new dual-PI3K/HDAC6 inhibitor, LASSBio-2208, were evaluated against PC3 prostate cancer cell line. Methods: A MTT assay was used to assess the cell viability. Annexin V/propidium iodide (PI) was used to detect apoptotic cell death and to analyze the cell cycle distribution. Interleukin 6 (IL-6) levels were measured by ELISA. A cell scratch assay was performed to assess cell migration, and the expression of proteins was estimated by Western blotting. Results: LASSBio-1911 and LASSBio-2208 exert cytotoxic effects against PC3 cells. However, LASSBio-2208 was demonstrated to be more potent than LASSBio-1911. The apoptosis assays showed that both compounds trigger apoptotic processes and cause the arrest of cells in the G2/M phase of the cell cycle. The Western blot analysis revealed that LASSBio-2208 significantly decreased the expression of p-JNK and JAK2. However, both compounds reduced the expression of p-STAT3, IL-6 secretion, and cell migration. Conclusions: LASSBio-1911 and LASSBio-2208 demonstrated significant activity in reducing cell viability and migration. These compounds can be further used as prototypes for the development of new potential anticancer alternative treatments.

Peroxiredoxin 2 oxidation reveals hydrogen peroxide generation within erythrocytes during high-dose vitamin C administration

Intravenous infusion of high dose (>10 g) vitamin C (IVC) is a common alternative cancer therapy. IVC results in millimolar levels of circulating ascorbate, which is proposed to generate cytotoxic quantities of H2O2 in the presence of transition metal ions. In this study we report on the in vitro and in vivo effects of millimolar ascorbate on erythrocytes. Addition of ascorbate to whole blood increased erythrocyte intracellular ascorbate approximately 35-fold. Within 10 min of ascorbate addition, we detected increased oxidation of erythrocyte peroxiredoxin 2 (Prx2), a major thiol antioxidant protein and a sensitive marker of H2O2 production. Up to 50% of Prx2 was present in the oxidised form after 60 min. The presence of extracellular catalase, removal of plasma or the addition of a metal chelator did not prevent ascorbate-induced Prx2 oxidation, suggesting that the H2O2 responsible for Prx2 oxidation was generated within the erythrocyte. Ascorbate is known to increase the rate of haemoglobin autoxidation and H2O2 production. Through spectral monitoring of oxidised haemoglobin we estimated a generation rate of 15 μM H2O2/min inside erythrocytes. We also investigated changes in erythrocyte ascorbate concentration and Prx2 oxidation following IVC infusion in a cohort of patients with cancer. Plasma ascorbate levels ranged from 7.8 to 35 mM immediately post infusion, while erythrocyte ascorbate levels reached 1.5–3.4 mM 4 h after beginning infusion. Transient oxidation of erythrocyte Prx2 was observed. We conclude that erythrocytes accumulate ascorbate during IVC infusion, providing a significant reservoir of ascorbate, and this ascorbate increases H2O2 generation within the cells. The consequence of increased erythrocyte Prx2 oxidation warrants further investigation.

Anticancer, anticholinesterase and antidiabetic activities of tunceli garlic (Allium tuncelianum): determining its phytochemical content by LC–MS/MS analysis

We aimed to investigate the phytochemical content and pharmaceutical activity of methanol extracts of Allium tuncelianum (MAT). In this study, phytochemical contents of MAT were analyzed by liquid chromatography mass-spectrometry (LC–MS/MS) technique. Anticancer activity was determined on six different cell lines. By flow cytometric method, apoptotic activity was examined with annexin V in human prostate carcinoma (PC3) cell lines where the highest cytotoxic activity was observed. Real Time PCR was used to investigate the molecular genetic size of the effect. Anticholinesterase and antidiabetic activities were performed using enzyme inhibition technique. Enzyme inhibitory activity of MAT was determined using AChE, α-glucosidase enzymes. In these extracts, “μg Analyte/g MAT” as its unit; quinic acid (6458.45 ± 2.389), malic acid (4187.25 ± 0.544) and vanilic acid (349.4 ± 0.052) were found to be major components. The highest cytotoxic activity was found in PC3 cells (IC50: 105.72 µg/mL). Therefore, the mechanism of apoptotic effect in this cell line was also investigated. In a statistically meaningful proportion, MAT increased Caspase 3 and Caspase 9 gene expressions and suppressed IL6, IL8, MMP2 and MMP9 gene expressions. On the other hand, MAT demonstrated effective inhibition effects against AChE (IC50: 11.25 μg/mL), and α-glycosidase (IC50: 9.85 μg/mL) enzymes. As a result, it can be argued that Allium tuncelianum can be used as an alternative treatment for prostate cancer, diabetes and some neurodegenerative diseases.

Heterologous Expression of Interferon α-2b in Lactococcus lactis and its Biological Activity against Colorectal Cancer Cells

Lita Meilina, Sri Budiarti , Apon Zaenal Mustopa*, Huda Shalahudin Darusman, Lita Triratna, Muhammad Ajietuta Nugraha, Muhammad Sabiq Bilhaq, and Ratih Asmana Ningrum. Microbiol. Biotechnol. Lett. 2021;49:75-87. https://doi.org/10.48022/mbl.2009.09008

Incorporation of Dual-Stimuli Responsive Microgels in Nanofibrous Membranes for Cancer Treatment by Magnetic Hyperthermia.

The delivery of multiple anti-cancer agents holds great promise for better treatments. The present work focuses on developing multifunctional materials for simultaneous and local combinatory treatment: Chemotherapy and hyperthermia. We first produced hybrid microgels (MG), synthesized by surfactant-free emulsion polymerization, consisting of Poly (N-isopropyl acrylamide) (PNIPAAm), chitosan (40 wt.%), and iron oxide nanoparticles (NPs) (5 wt.%) as the inorganic component. PNIPAAm MGs with a hydrodynamic diameter of about 1 μm (in their swollen state) were successfully synthesized. With the incorporation of chitosan and NPs in PNIPAAm MG, a decrease in MG diameter and swelling capacity was observed, without affecting their thermosensitivity. We then sought to produce biocompatible and mechanically robust membranes containing these dual-responsive MG. To achieve this, MG were incorporated in poly (vinyl pyrrolidone) (PVP) fibers through colloidal electrospinning. The presence of NPs in MG decreases the membrane swelling ratio from 10 to values between 6 and 7, and increases the material stiffness, raising its Young modulus from 20 to 35 MPa. Furthermore, magnetic hyperthermia assay shows that PVP-MG-NP composites perform better than any other formulation, with a temperature variation of about 1 °C. The present work demonstrates the potential of using multifunctional colloidal membranes for magnetic hyperthermia and may in the future be used as an alternative treatment for cancer.

GM-CSF-producing lymphocytes in tumor-draining lymph nodes of patients with bladder cancer.

Bladder cancer (BC) is the tenth common cancer worldwide. Despite progress in treatment and the use of chemotherapoeutic drugs, the survival rate of BC patients is still low. Manipulation of the immune system was recently introduced as an interesting alternative treatment for this immunogenic cancer with fewer side effects. Accordingly, in the present study, we assessed the frequency of GM-CSF-producing lymphocytes in tumor-draining lymph nodes (TDLNs) of BC patients and evaluated their relationship with clinicopathological factors and survival rate. Fifty-four patients with BC who had received no treatment were recruited. Mononuclear cells were isolated from fresh homogenized lymph nodes by centrifugation over Ficoll-Hypaque, activated and subsequently analyzed by flow cytometry for the cell surface expression of CD4 and CD8 and the intracellular production of GM-CSF. Flow cytometric analysis revealed that 4.97 ± 2.7% of lymphocytes in TDLNs of patients with BC produced GM-CSF. The mean frequency of GM-CSF-producing cells was 5.5% among CD4+ lymphocytes and 11.7% in the CD8+ population. Elevated frequencies of GM-CSF-producing lymphocytes, as well as a higher production of GM-CSF by CD4+ lymphocytes was observed in the patients with tumor-free lymph nodes, as compared to those with at least one tumor-infiltrated lymph node (p <0.05). On the other hand, the lower frequency of GM-CSF-producing CD4+ lymphocytes (ThGM) was associated with improved overall, but not one-year, survival. No other significant relationship was observed between clinicopathological parameters and the frequency of GM-CSF-producing subsets. Collectively, our findings suggest a protective role for GM-CSF in the early stages of BC; however, the unfavorable association of ThGM frequency with survival rate may imply a more complex role for this cytokine in BC.