3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), identified from the Pacific oyster Crassostrea gigas, has dual properties to block oxidative stress as a radical scavenger and a potential cell function regulator. DHMBA has been shown to suppress adipogenesis, inflammatory activated macrophages, osteoclastogenesis, osteoblastic bone formation, and anti-cancer activity in vitro, suggesting its role in preventing and treating several diseases. The toxicological effects of DHMBA may be important for the development of its pharmacological application. However, the toxicity of DHMBA has not been determined. To evaluate the no-observed-adverse-effect level of synthetic DHMBA, this study was conducted in male and female rats at a single oral dose of DHMBA 500, 1000, or 2000 mg/kg body weight, for 14 days at 30, 100, 300, and 1000 mg/kg/day, and for 91 days at the DHMBA 1, 5, and 25 mg/kg/day dose in male and female rats. The toxicological effects of DHMBA were evaluated by analyzing the changes in general condition, including body weight, behavior, body temperature, abnormal gait, decreased mobility, decreased alternate, slowed approach response, slowed touch response, slowed auditory response, abnormal righting reflex in air, and decreased abdominal muscle tone, blood biochemistry test, macroscopic pathological examination, organ weight, histopathological examination, inflammatory changes, or obvious abnormalities in the hematopoietic system. As a result, this study demonstrated that the no-observed-adverse-effect level of synthetic DHMBA in male and female rats was 25 mg/kg/day when administered for 91 days. This result may provide important toxicological information in the use of the DHMBA as a pharmacological tool.

2025-03-01·Chemical Biology & Drug Design

The Potent Antioxidant 3,5‐Dihydroxy‐4‐Methoxybenzyl Alcohol Reveals Anticancer Activity by Targeting Several Signaling Pathways in Bone Metastatic Human Breast Cancer MDA‐MB‐231 Cells

Article

作者: Watanabe, Hideaki ; Watanabe, Mitsugu ; Yoshiike, Kenji ; Yamaguchi, Masayoshi

ABSTRACTHuman breast cancer is the leading cause of cancer‐related death in women. Bone metastatic human breast cancer MDA‐MB‐231 cells are triple negative. The novel marine factor 3,5‐dihydroxy‐4‐methoxybenzyl alcohol (DHMBA), a potent antioxidant, has been shown to prevent oxidative stress by scavenging free radicals in cells. This study investigates the effects of DHMBA on MDA‐MB‐231 cells in vitro. MDA‐MB‐231 cells were cultured with DHMBA (0.1–100 μM). DHMBA blocked the growth and stimulated the death of MDA‐MB‐231 cells, resulting in reduced cell numbers. DHMBA treatment decreased PI3‐kinase 100α, Akt, MAPK, phosphor‐MAPK, and mTOR and increased p53, p21, and Rb, which are suppressors in cell growth. DHMBA inhibited metastatic activity, including adhesion and migration of MDA‐MB‐231 cells. Coculture with MDA‐MB‐231 cells resulted in decreased growth and stimulated death of osteoblastic MC3T3‐E1 cells and macrophage RAW264.7 cells, suggesting that cancer cells affect the bone microenvironment. Production of TNF‐α, which is the mediator in the bone microenvironment, in MDA‐MB‐231 cells was inhibited by DHMBA treatment. Crosstalk between cancer cells and cells in the bone microenvironment was blocked by culture with DHMBA. DHMBA may inhibit the activity of triple‐negative human breast cancer cells, providing a useful tool for the treatment of breast cancer.

2025-01-01·Chemico-Biological Interactions

The novel marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol exhibits anticancer activity by regulating multiple signaling pathways in human glioblastoma cells: Blocking EGF signaling

Article

作者: Kuroki, Katsuya ; Yoshiike, Kenji ; Watanabe, Mitsugu ; Yamaguchi, Masayoshi ; Watanabe, Hideaki

Glioblastoma is the most common adult malignant brain tumor. This tumor is aggressive and the most lethal. Trials to improve the outcome of patients with this tumor remain critical. There are no effective therapies for malignant glioma. Glioblastoma is characterized by ligand-independent overexpression of epidermal growth factor (EGF) receptors. EGF receptor signaling can promote tumorigenesis by increasing cell proliferation and tissue invasion and by inhibiting apoptosis of cancer cells. The marine factor 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA) has been shown to block oxidative stress by scavenging free radicals in various cell types. This study investigates the effects of DHMBA on human glioblastoma cells in vitro. Glioblastoma cells were cultured in DMEM-low glucose containing 10 % fetal bovine serum (FBS) in the presence of DHMBA (0.1-250 μM). Culturing with DHMBA significantly suppressed cell proliferation in the presence of FBS or EGF. Mechanistically, DHMBA treatment significantly decreased the levels of PI3-kinase 100α, Akt, MAPK, phosphor-MAPK, and mTOR, which are promoters of cell growth, and increased the levels of tumor suppressors p53, p21, and Rb, leading to the reduction of cancer cell growth. DHMBA treatment significantly stimulated the death of glioblastoma cells by increasing the levels of caspase-3 and cleaved caspase-3. In addition, culture with DHMBA significantly inhibited metastatic activity, including adhesion and migration of cancer cells. Thus, DHMBA may have inhibitory effects on the activity of human glioblastoma cells in vitro. This study may provide a new strategy for the treatment of glioblastoma tumors.

100 项与 DHMBA 相关的药物交易

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