Antitumor and radiosensitizing synergistic effects of apigenin and cryptotanshinone against solid Ehrlich carcinoma in female mice

Abstract

Considerable attention has been paid to the introduction of novel naturally occurring plant-derived radiosensitizer compounds in order to augment the radiation efficacy and improve the treatment outcome of different tumors. This study was therefore undertaken to evaluate the antitumor, antiangiogeneic, and synergistic radiosensitizing effects of apigenin, a dietary flavonoid, and/or cryptotanshinone, a terpenoid isolated from the roots of Salvia miltiorrhiza, against the growth of solid Ehrlich carcinoma in female mice. Apigenin (50 mg/kg body weight) and/or cryptotanshinone (40 mg/kg body weight) was intraperitoneally (i.p.) injected into non-irradiated or γ-irradiated (6.5 Gy whole-body γ-irradiation) solid Ehrlich carcinoma-bearing mice for 30 consecutive days. Investigations included molecular targets involved in proliferation, inflammation, angiogenesis, and tumor invasiveness. Treatment with apigenin and/or cryptotanshinone significantly suppressed the growth of solid Ehrlich carcinoma tumors and demonstrated a synergistic radiosensitizing efficacy together with γ-irradiation. These effects were achieved through downregulating the expression of angiogenic and lymphangiogenic regulators, including signal transducer and activator of transcription 3, vascular endothelial growth factor C, and tumor necrosis factor alpha, suppressing matrix metalloproteinase-2 and -9 activities, which play a key role in tumor invasion and metastasis, and enhancing apoptosis via inducing cleaved caspase-3 and granzyme B levels. Histological findings of solid Ehrlich carcinoma tumors verified the recorded data. In conclusion, a synergistic radiosensitizing efficacy for apigenin and cryptotanshinone was demonstrated against Ehrlich carcinoma in the current in vivo murine model, representing therefore a potential therapeutic strategy for increasing the radiation response of solid tumors.

Role of Bee Venom and Melittin on Restraining Angiogenesis and Metastasis in γ-Irradiated Solid Ehrlich Carcinoma-Bearing Mice

“…In order to grow Ehrlich solid tumor (EST) in the thigh, 0.2 mL EAC cells (2.5 × 106 cells/mouse) were subcutaneously inoculated at the right thigh of the lower female mouse limb. 5 …”

“…and metastasis, as well as angiogenesis, all of which are well-established cancer hallmarks. 5 Apoptosis is a cellular cycle, organized and coordinated, occurring under physiological and pathological conditions. It is the main event that regulates the occurrence and/or spread of cancer.…”

CYP1B1 as a therapeutic target in cardio-oncology

“…Moreover, apigenin alongside genistein and quercetin enhanced radiation-induced cell death by decreasing DNA damage renewal and cell repopulation, demonstrating higher antitumor activities [327]. Additional in vivo studies also demonstrated the radiosensitizing effects of apigenin in Ehrlich carcinoma-bearing mice exposed to whole body γ irradiation via the down-regulation of angiogenic regulators such as vascular endothelial growth factor-C (VEGF-C), down-regulation of matrix metalloproteinase-2 (MMP2), and the enhancement of apoptosis [328]. The radiosensitizing effects of quercetin have also been demonstrated in DLD-1 human colorectal cancer xenograft model in vivo and in HeLa and MCF-7 cells in vitro [329,330].…”

Tumoricidal Effect of Trigonella foenum-graceum Extract and Selenium Nanoparticles on Ehrlich Carcinoma Bearing Mice

“…According to the model of granule-mediated apoptosis, killing involves degranulation and subsequent transfer of these proteases into the cytoplasm of the target cell, where they rapidly induce apoptosis [35]. This process is inhibited in cancer, which leads to the accumulation of various genetic unstable cells [36].…”