Biology subjects

Wilke, D. V.

Publications and source records attributed to Wilke, D. V..

6 recordsLinked to original sources

bioRxiv2025

Anticancer potential of piericidin A1 and derivatives isolated from Streptomyces sp. associated with Palythoa variabilis from Brazilian Reefs

Marine holobionts are prolific sources of bioactive natural products. Previously, our group investigated cytotoxic compounds in zoantharians of the genus Palythoa and, herein, we further explored the anticancer potential of marine bacteria associated with P. variabilis. After isolating 10 culturable bacterial strains, we screened for cytotoxic activity on metastatic prostate tumor cells (PC-3/M) using the MTT assay. The crude extract of one of the strains (BRA-035), identified as Streptomyces sp., was selected due to its bioactivity profile and submitted to cytotoxicity-guided fractionation. This approach allowed us to isolate piericidin A1 and identify other 2 piericidin derivatives. Piericidin A1 displayed a wide range of potency, with IC50 varying from pM to low nM for several tumor cells (OVCAR, PC-3, PC-3/M, HCT-116) or non active (IC50 >12uM) for leukemia cell line (HL-60) and murine melanoma (B16-F10). Overall, our findings demonstrate that P. variabilis hosts bacteria with biotechnological potential, confirming piericidin A1 as a promising candidate for anticancer applications.

pharmacology and toxicology↗

bioRxiv2023

SULFATED POLYSACCHARIDE FROM BROWN ALGAE DICTYOTA CARIBAEA STIMULATES MACROPHAGES TO AN ANTITUMORAL PHENOTYPE

Fucoidans are sulfated polysaccharides capable of exerting biological activities such as antitumor and immunomodulatory effects. Previous studies demonstrated the antitumor activity of non-cytotoxic fucoidan from the seaweed Dictyota caribaea (Dc-SP) in vivo. Macrophages (M{varphi}) are innate immune cells capable of promoting or inhibiting tumor growth depending on the stimulus. This study aimed to evaluate the immunostimulant activity of Dc-SP on murine M{varphi} (RAW264.7) in vitro. Dc-SP was assessed for its ability to modify cell viability and stimulate the production of antitumor markers on RAW264.7 cells. Dc-SP induced an increase (p<0.05) in the production of NO and cytokines TNF-, IL-1{beta}, and IL-10. The exposure of M{varphi} to Dc-SP also increased (p<0.05) the expression of M1 macrophage markers such as iNOS, CD86, and MHC II. The antiproliferative activity of RAW264.7 cells stimulated with DC-SP on melanoma cells (B16-F10) in vitro. Dc-SP did not exhibit direct cytotoxicity on B16-F10, however, the conditioned medium (CM) of RAW264.7 previously stimulated with Dc-SP (CM-Dc-SP) showed antiproliferative activity on tumor cells. B16-F10 incubated with CM-Dc-SP showed a cytostatic profile, tumor cells did not alter membrane integrity, however, suffered morphological changes such as cell shrinkage and high granularity. In conclusion, Dc-SP stimulated M{varphi} to an antitumor phenotype.

immunology↗

bioRxiv2021

Chromomycin A5 induces bonafide immunogenic cell death in metastatic melanoma

Some first-line cytotoxic chemotherapics, e.g. doxorubicin, paclitaxel and oxaliplatin, induce activation of the immune system through immunogenic cell death (ICD). Tumor cells undergoing ICD function as a vaccine, releasing damage-associated molecular patterns (DAMPs), which act as adjuvants, and neoantigens of the tumor are recognized as antigens. ICD induction is rare, however it yields better and long-lasting antitumor responses to chemotherapy. Advanced metastatic melanoma (AMM) is incurable for more than half of patients. The discovery of ICD inducers against AMM is an interesting drug discovery strategy with high translational potential. Here we evaluated ICD induction of four highly cytotoxic chromomycins A (CA5-8). B16-F10, a metastatic melanoma cell line, treated with CA5-8 and doxorubicin exhibited ICD features such as autophagy and apoptosis, externalization of calreticulin, and releasing of HMGB1. However, CA5-treated cells had the best profile, also inducing ATP release, ERp57 externalization, phosphorylation of eIF2 and altering expression of transcription of genes related to autophagy, endoplasmic reticulum stress, and apoptosis. Bonafide ICD induction by CA5 was confirmed by a C57BL/6 mice vaccination assay with CA5-treated cells. These findings support a high potential of CA5 as an anticancer candidate against AMM.

immunology↗

bioRxiv2021

Sulfated polysaccharides from red seaweed Gracilaria cornea induce macrophages polarization to an antitumor M1 phenotype

Marine seaweeds are a rich source of sulfated polysaccharides with several biological activities, including antitumor effect. Some polysaccharides are also described to activate macrophages (M{phi}s) to an antitumor M1-like phenotype. Here, we evaluated the capacity of sulfated galactans (SGs) extracts obtained from three seaweed species, Gracilaria cornea (Gc-E), Gracilaria birdiae (Gb-E), and Solieria filiformis (Sf-E), to activate the M{phi}s antitumor M1 phenotype. The nitric oxide production, MHCII, and CD86 (M1 markers) were evaluated to screening the bioactive SGs profile on murine M{phi}s (RAW 264.7 cells). The direct SGs antiproliferative effect was tested on melanoma B16-F10 cells. In another experimental setting, B16-F10 cells were incubated with a conditioned medium obtained from M{phi}s exposed to SGs. The three SGs tested induced NO release. Sf-E directly inhibited B16-F10 cells proliferation compared with the saline group, but Gc-E and Gb-E failed to inhibit cell proliferation. Notably, a conditioned medium (CM) of M{phi}s incubated with Gc-E and Sf-E, but not of Gb-E, inhibited the proliferation of B16-F10 cells. Gc-E also induced TNF- release and increase of M1 markers such as iNOS, MHCII, and CD86. Therefore, Gc-E activates M{phi}s to M1 phenotype, which in turn releases a factor that inhibits B16-F10 proliferation.

pharmacology and toxicology↗

bioRxiv2020

ANTITUMOR SULFATED POLYSACCHARIDES FROM BROWN ALGAE Dictyota caribaea

Sulfated polysaccharides (SP) are a complex group of bioactive molecules able to inhibit tumor growth. SP increase the effectiveness of chemotherapy and reduce some side effects. Brown algae produce SP with several biological activities including antitumor. This work aimed to investigate the antitumor effect of SP from the brown algae Dictyota caribaea (Dc-SP). Dc-SP were extracted with proteolytic enzyme and supernatant was precipitated with increasing concentrations of ethanol. Antiproliferative activity of Dc-SP was tested by the MTT assay against colon cancer (HCT 116) and metastatic melanoma (B16-F10) cell lines. The antitumor effect was evaluated on Swiss mice transplanted with sarcoma 180 tumor and treated i.p. during 7 days with saline or Dc-SP (25 and 50 mg/kg/animal). Dc-SP did not exhibit cytotoxicity in vitro, however the Dc-SP-treated mice depicted up to 50% tumor growth inhibition. Dc-SP treatment induced spleen weight increasing along with intense white pulp disorganization. Furthermore Dc-SP did not depict hepatic toxicity, nephrotoxicity nor leukopenia and did induce increase of platelets count. Altogether, these results represent a promising antitumor host dependent effect induced by Dc-SP.

pharmacology and toxicology↗

bioRxiv2020

Human keratinocyte (HaCaT) stimulation and healing effect of the methanol fraction from the decoction from leaf from Sideroxylon obtusifolium (Roem. & Schult.) T.D. Penn on experimental burn wound model

The larger number of plants, with therapeutic potential, popularly used in Northeastern Brazil is due to their easy access and the great Brazilian biodiversity. Previously, was demonstrated that the methanol fraction from Sideroxylon obtusifolium (MFSOL) promoted an anti-inflammatory and healing activity in excisional wounds. Thus, this work aimed to investigate the healing effects of MFSOL on human keratinocytes cells (HaCaT) and experimental burn model injuries. HaCaT cells were used to investigate migration and proliferation of cell rates. Female Swiss mice were subjected to second-degree superficial burn protocol and divided into four treatment groups: Vehicle (cream-base), 1.0% Silver Sulfadiazine (Sulfa), and 0.5% or 1.0% MFSOL cream (CrMFSOL). Samples were collected for quantification of the inflammatory mediators and histological analyses after 3, 7 and 14 days on evaluation. As result, MFSOL (50 g/ml) stimulated HaCaT cells by increasing proliferation and migration rates. Moreover, CrMFSOL 0.5% attenuated myeloperoxidase (MPO) activity and also stimulated the release of IL-1{beta} and IL-10, after 3 days with treatment. CrMFSOL 0.5% enhanced wound contraction, promoted tissue remodeling improvement and highest collagen production after 7 days, and VEGF release after 14 days. Therefore, MFSOL evidenced the stimulation of human keratinocyte (HaCaT) cells and improvements on wound healing via inflammatory modulation on burn injuries.

pharmacology and toxicology↗