Dewi Firli Rahmah Primula, Shoukat Nadia, Alifiyah Na'ilah Insani, Wahyuningsih Sri Puji Astuti, Rosyidah A'liyatur, Prenggono Muhammad Darwin, Hartono Hartono
Department of Biology, Faculty of Science and Technology, Universitas Airlangga, Surabaya 60115, Indonesia.
Research Center for Vaccine and Drug, National Research and Innovation Agency (BRIN), Bogor 16911, Indonesia.
Heliyon. 2022 Nov 5;8(11):e11418. doi: 10.1016/j.heliyon.2022.e11418. eCollection 2022 Nov.
Annonaceous acetogenins have been reported to have anti-cancer properties but low viability. In this study, we aimed to investigate the potency of nanodiamonds to be employed as a carrier of annonacin to help increase its viability and inhibit the growth of breast cancer cells.
The annonacin was coupled with nanodiamond and characterized using UV-Vis spectrophotometer, FTIR, SEM, and PSA, and determined their stability and drug release. A cell growth inhibition assay and cell migration assay was performed using the breast cancer MCF7 and T747D cell lines, and in vivo analysis was performed in rats (). MCF7 and T747D cells were treated with 12.5 μg/mL annonacin coupled with nanodiamonds for 24 and 48 h and further analyzed by MTT, cell migration, and reactive oxygen species (ROS) assays. Twenty-five female rats were divided into five groups. Breast cancer was induced using two intraperitoneal doses of N-nitroso-N-methylurea (NMU) (50 and 30 mg/kg body weight). Annonacin coupled with nanodiamonds was administered by intraperitoneal injection (17.5 mg/kg body weight) for 5 weeks, one injection per 3 days.
Administration of annonacin coupled with nanodiamonds significantly reduced MCF7 cell growth and reactive oxygen species (ROS) levels. The in vivo study showed that administration of annonacin coupled with nanodiamonds significantly reduced PI3KCA levels and increased p53 expression, reduced cancer antigen-15-3 (CA-15-3) levels in serum, increased caspase-3 expression, reduced Ki-67 levels, and reduced the thickness of the mammary ductal epithelium.
Collectively, this study demonstrated the effectiveness of nanodiamonds as a carrier of annonacin to inhibit breast cancer cell growth through inhibition of the PI3K/Akt signaling pathway.
番荔枝内酯已被报道具有抗癌特性，但活性较低。在本研究中，我们旨在研究纳米金刚石作为annonacin载体的潜力，以帮助提高其活性并抑制乳腺癌细胞的生长。
将annonacin与纳米金刚石偶联，并用紫外可见分光光度计、傅里叶变换红外光谱仪、扫描电子显微镜和粒度分析仪对其进行表征，并测定其稳定性和药物释放情况。使用乳腺癌MCF7和T747D细胞系进行细胞生长抑制试验和细胞迁移试验，并在大鼠体内进行分析（）。用12.5μg/mL与纳米金刚石偶联的annonacin处理MCF7和T747D细胞24和48小时，并通过MTT、细胞迁移和活性氧（ROS）试验进一步分析。25只雌性大鼠分为五组。使用两次腹腔注射N-亚硝基-N-甲基脲（NMU）（50和30mg/kg体重）诱导乳腺癌。将与纳米金刚石偶联的annonacin通过腹腔注射（17.5mg/kg体重）给药5周，每3天注射一次。
给予与纳米金刚石偶联的annonacin可显著降低MCF7细胞生长和活性氧（ROS）水平。体内研究表明，给予与纳米金刚石偶联的annonacin可显著降低PI3KCA水平并增加p53表达，降低血清中癌抗原-15-3（CA-15-3）水平，增加caspase-3表达，降低Ki-67水平，并减少乳腺导管上皮厚度。
总体而言，本研究证明了纳米金刚石作为annonacin载体通过抑制PI3K/Akt信号通路抑制乳腺癌细胞生长具有有效性。
