Colorectal cancer (CRC) is a significant public health challenge, with 5-fluorouracil (5-FU) resistance being a major obstacle to effective treatment. Despite advancements, resistance to 5-FU remains formidable due to complex mechanisms such as alterations in drug transport, evasion of apoptosis, dysregulation of cell cycle dynamics, tumor microenvironment (TME) interactions, and extracellular vesicle (EV)-mediated resistance pathways. Traditional chemotherapy often results in high toxicity, highlighting the need for alternative approaches with better efficacy and safety. Phytochemicals (PCs) and EVs offer promising CRC therapeutic strategies. PCs, derived from natural sources, often exhibit lower toxicity and can target multiple pathways involved in cancer progression and drug resistance. EVs can facilitate targeted drug delivery, modulate the immune response, and interact with the TME to sensitize cancer cells to treatment. However, the potential of PCs and engineered EVs in overcoming 5-FU resistance and reshaping the immunosuppressive TME in CRC remains underexplored. Addressing this gap is crucial for identifying innovative therapies with enhanced efficacy and reduced toxicities. This review explores the multifaceted mechanisms of 5-FU resistance in CRC and evaluates the synergistic effects of combining PCs with 5-FU to improve treatment efficacy while minimizing adverse effects. Additionally, it investigates engineered EVs in overcoming 5-FU resistance by serving as drug delivery vehicles and modulating the TME. By synthesizing the current knowledge and addressing research gaps, this review enhances the academic understanding of 5-FU resistance in CRC, highlighting the potential of interdisciplinary approaches involving PCs and EVs for revolutionizing CRC therapy. Further research and clinical validation are essential for translating these findings into improved patient outcomes.

Acute myeloid leukemia (AML) is a malignant disease progressed from abnormal production of immature myeloid cells, which is often associated with concurrent infections after diagnosis. It was widely established that infections are the major contributors to mortality in this group due to the prevalency of neutropenia. Gram-negative Burkholderia pseudomallei is the causative agent of melioidosis. This disease had been reported in several neutropenic cancer patients undergoing chemotherapy resulting in severe clinical presentations and high mortalities which is in need of critical attention. Studies show that cytokines are important mediators of melioidosis progression and low neutrophil counts are associated with progression of its severity. However, to date, there are no reports on cytokine production in neutropenic cancer patients who are prone to melioidosis. Hence, here we assessed the cytokine production in neutropenic AML patients by introducing B. pseudomallei to their peripheral blood mononuclear cell (PBMC) culture in vitro. We observed that inflammatory response related cytokines namely TNF-α, IFN-γ IL-6 and IL-10 were highly circulated in infected PBMCs suggesting that these cytokines may play important roles in the progression of severity in melioidosis infected neutropenic patients.

Introduction: The composition of the honey depends on the intrinsic and extrinsic factors, including place of origin, the floral types, the season and the storage conditions. This study compared the anticancer potential, quality, antioxidant and phytochemical between unprocessed stingless bee honey (SBH) and honeybee honey (HBH) from the same environmental factors including place of nest, floral type (Acacia), harvesting month (August) and storage conditions (<5°C). Materials and methods: To measure quality, 5-hydroxymethylfurfural (HMF) and diastase activity were determined, followed by total phenolic content (TPC) and total flavonoid content (TFC) for phytochemicals. Antioxidant activity was assessed via 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. Cytotoxicity towards cervical cancer cell line (HeLa) was measured using a 2-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay (IC50). Results: The results indicated that HBH exhibited significantly higher diastase activity (2.17 ± 0.07 DN), TPC (338.95 ± 3.49 mg GAE/kg), DPPH scavenging activity EC50 (80.06 mg/ml) and MTT activity IC50 (64.80 mg/ml) towards HeLa as compared to SBH with absence of diastase activity, TPC (250.60 ± 3.98 mg GAE/kg), DPPH scavenging activity EC50 (165.80 mg/ml) and MTT activity IC50 (75.76 mg/ml). However, there were no significant differences in HMF and TFC between HBH and SBH. Conclusion: Therefore, the present study found that HBH demonstrates better antioxidant capacity, anticancer potential and phenolic content as compared to SBH.

The role of hyperforin in combination anticancer therapy remain unknown. In this study, several doses of combination treatment (paclitaxel and hyperforin) were introduced to the Michigan Cancer Foundation (MCF)-7 cell culture for 24 h. The effectiveness of the drug’s combination effect was determined by the combination index (CI)followed by the anticancer effect through apoptosis, reactive oxygen species (ROS), lactate dehydrogenase (LDH) and caspase 8 assays. It was found that combined doses of paclitaxel (7, 6, 5, 4 µg/mL) and doses of hyperforin (1, 2, 3 and 4 µg/mL) enhanced synergistic growth inhibitory effect. (Hy: 4 µg/mL & Pa: 4 µg/mL) was selected as suitable dose with lowest CI and it significantly induced changes to MCF-7 cell morphology and led to apoptosis with increased in the high level of ROS, LDH and caspase 8 compared to singly treated hyperforin. This study provides the basis for elucidation of combination of hyperforin and paclitaxel on animal models.

Background/Aim: Isoniazid is an antibiotic used for the treatment of tuberculosis. Previously, we found that the isoniazid derivative (E)-N’-(2,3,4-trihydroxybenzylidene) isonicotinohydrazide (ITHB4) could be developed as novel antimycobacterial agent by lead optimization. We further explored the ability of this compound compared to zerumbone in inhibiting the growth of MCF-7 breast cancer cells. Materials and Methods: Cytotoxicity was measured by the MTT assay and further confirmed via apoptosis, ROS, cell cycle, DNA fragmentation and cytokine assays. Results: ITHB4 demonstrated a lower IC₅₀ compared to zerumbone in inhibiting the proliferation of MCF-7 cells. ITHB4 showed no toxicity against normal breast and human immune cells. Apoptosis assay revealed that ITHB4, at a concentration equal to the IC₅₀, induces apoptosis of MCF-7 cells and cell cycle arrest at the sub-G1 and G₂/M phases. ITHB4 triggered accumulation of intracellular ROS and nuclear DNA fragmentation. Secretion of pro-inflammatory cytokines induced inflammation and potentially immunogenic cell death. Conclusion: ITHB4 has almost similar chemotherapeutic properties as zerumbone in inhibiting MCF-7 growth, and hence provide the basis for further experiments in animal models.