aconitine and Breast-Neoplasms

As one of the most common malignancies in female dogs, no drugs have been developed specifically for the treatment of canine mammary carcinoma. In our previous study, a series of diterpenoid alkaloids derivatives were synthesized and exhibited good anti-proliferative activity in vitro against both normal and adriamycin-resistant human breast cancer cells lines. In this study, a series of structurally diverse aconitine-type alkaloids derivatives were also synthesized basing on the minimal modification principle, by modifying on A-ring, C-ring, D-ring, N-atom or salt formation on aconitine skeleton. Their anti-proliferative effects and mechanism on canine mammary cancer cells were investigated, exhibiting the importance of the substitution at A ring, the long chain ester at the C8, the hydroxyl group at the C13, the phenyl ring at the C14 and the N-ethyl group, while the methoxy group at the C1 and C16 showed little effect on the activity. The results of the proliferation, apoptosis and ultrastructure tests of the treated canine mammary carcinoma cells referred that the representative compound, aconitine linoleate (25) could block the cell cycle of canine mammary carcinoma cells in the G0/G1 phase, and exhibit the anti-proliferative effect by inducing apoptosis.

Topics: Aconitine; Alkaloids; Animals; Breast Neoplasms; Carcinoma; Diterpenes; Dogs; Female; Humans

To explore the inhibitory effects and to investigate the mechanisms of combined treatment of osthole, psoralen with aconitine on human breast cancer cell line MDA-MB-231BO.. The best inhibitory concentration of osthole, psoralen combined with aconitine on MDA-MB-231BO cells was obtained by stepwise regression analysis after adopting a uniform experiment design. The invasive activities were observed by transwell assays, and expressions of transforming growth factor-β1 (TGF-β1), Smad2, Smad3, Smad4, Smad7, nuclear factor-κB (NF-κB) and receptor activator of NF-κB ligand (RANK) mRNAs were analyzed by real-time quantitative polymerase chain reaction.. The optimal combination concentrations of osthol, psoralen and aconitine were 6.44, 8.89 and 9.44 μg/mL, respectively. Cell invasion was significantly inhibited after 24 hours of treatment using the combination drugs and zoledronic acid. TGF-β1, Smad2, Smad3, Smad4, Smad7, NF-κB and RANK mRNA expressions of the optimal combination group and zoledronic acid group were significantly reduced compared with the control group (P<0.01). Furthermore, TGF-β1, Smad2, Smad3, Smad4, Smad7, NF-κB and RANK mRNA expressions of the optimal combination group were significantly lower than those of the weak combination group (P<0.01).. Combination treatment of osthole, psoralen with aconitine can inhibit cancer cell invasion, which is a result of alteration of the TGF-β/Smad signaling pathway and down-regulation of NF-κB and RANK expressions.

Topics: Aconitine; Breast Neoplasms; Cell Line, Tumor; Coumarins; Female; Ficusin; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Invasiveness; NF-kappa B; Receptor Activator of Nuclear Factor-kappa B; Signal Transduction; Smad Proteins

Breast cancer is the fourth most frequent cause of death, and it is currently the most frequent cause of death among Japanese women. As to breast cancer therapy, lengthy hormonal therapy is very important for the treatment and prevention of recurrence. Aromatase inhibitors (AIs) are the initial drug of choice for postoperative adjuvant therapy of breast cancer in Japan. AIs require long-term use and occasionally cause serious side-effects. In this report, the effects of Kampo medicines (Japanese traditional medicines) on AIs-induced side-effects are described.. A 55-year-old woman visited the Kampo outpatient department of Chiba University Hospital for atypical genital bleeding and arthralgia. At the age of 54, she suffered from left breast cancer and underwent left total mastectomy followed by chemotherapy for 6 months. Afterwards, 1 mg/day of anastrozole, one of the AIs, was used for therapy. Three (3) months later, atypical genital bleeding from vaginal mucosa and joint pains of bilateral hands and knees occurred as side-effects of anastrozole. Her attending doctor could only prescribe nonsteroidal external medicine for the inflammation of vaginal mucosa and do close follow-up. However, her symptoms showed no improvement.. Her deficiency of both ki (qi) and ketsu (Blood) was diagnosed based on Kampo diagnostics. Juzentaihoto was used for treatment. After taking juzentaihoto for 5 weeks, the atypical genital bleeding disappeared, and she no longer need topical medicine. Because her arthralgia showed no improvement, powdered processed aconitine root was added. After taking 3.0 g/day of this medication, her arthralgia almost completely disappeared.. Controlling the side-effects is a clinical issue from the viewpoint of adherence to drug treatment. Kampo therapy should be considered one of the choices for side-effects in the process of cancer treatment.

Topics: Aconitine; Aconitum; Anastrozole; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Arthralgia; Breast Neoplasms; Chemotherapy, Adjuvant; Drugs, Chinese Herbal; Female; Hemorrhage; Humans; Medicine, Kampo; Middle Aged; Mucous Membrane; Nitriles; Phytotherapy; Qi; Triazoles; Vagina