The effect-enhancing and toxicity-reducing activity of Hypericum japonicum Thunb. extract in murine liver cancer chemotherapy

Abstract

Abstract. Chinese herbs are potential sources of antitumor drugs with immunoregulatory activity and few adverse effects. In the present study, we investigated whether the Hypericum japonicum Thunb. (HJT) extract enhanced the efficacy of 5-fluorouracil (5-FU) treatment in murine liver tumor xenografts and reduced toxicity of chemotherapy in hepatoma H22-bearing mice. Tumor weight and inhibition rate, thymus and spleen indices, as well as white blood cell (WBC) count were calculated. The phagocytic function of macrophages was assessed by observing peritoneal macrophages phagocytized chicken red blood cells (RBC). Body weight and toxic reactions of the chemotherapeutic and life prolongation rate were investigated in the mice. Results demonstrated that the HJT extract significantly enhanced the tumor inhibition rate of 5-FU, improved the immune function, reduced the toxic effects and prolonged the survival time in the tumor-bearing mice. Taken together, these results indicated that the HJT extract has a synergistic tumor-inhibiting effect with 5-FU, is able to reduce the toxic side effects and is likely to be safe and efficacious for use in antitumor therapy. IntrodutionLiver cancer is a malignant disease with a high incidence and mortality, and is often diagnosed at an advanced stage (1). Common therapies, such as surgical resection, percutaneous or transarterial interventions are of limited efficacy (2), as chemotherapy, one of the main measures for a comprehensive treatment, may induce adverse effects such as bone marrow suppression, gastrointestinal reactions and lowered immunological function.Several Chinese herbs have been identified as potential sources of antitumor drugs (3-5). The effect-enhancing and toxicity-reducing activity of Chinese herbs in radiotherapy and chemotherapy of tumors was previously confirmed (6,7). However, no studies focusing on the antitumor and toxicity-reducing effects of Hypericum japonicum Thunb. (HJT) have been reported thus far. Therefore, the present investigation was conducted to ascertain whether the HJT extract enhanced the efficacy of 5-fluorouracil (5-FU) treatment in murine liver tumor xenografts, and reduced toxicity of chemotherapy in tumor-bearing mice. Materials and methodsReagents. RPMI-1640 medium, fetal bovine serum (FBS), penicillin G and streptomycin were obtained from Invitrogen Corp. (Carlsbad, CA, USA). 5-FU was obtained from the Shanghai Xudong Haipu Pharmaceutical Co., Ltd. (Shanghai, China). Murine H22 hepatoma cells were purchased from the Shanghai Institute of Cell Biology at the Chinese Academy of Sciences (Shanghai, China). Animals. Institute of Cancer Research (ICR) mice(male/female, 50-50%; weight, 20±2 g) were purchased from the Experimental Animal Center, Zhengzhou University (Zhengzhou, China). The animals were kept in a standard laboratory, under a 12-h light/dark cycle, at room temperature (20±2˚C), in a humid (75±15%) and filtered laminar air flow-controlled room in the animal facility of the Experimental Animal Center of the Zhengzhou University...

Antitumor effects of baicalin on ovarian cancer cells through induction of cell apoptosis and inhibition of cell migration in vitro

“…In recent years, many bioactive phytochemicals have been observed to exhibit anti-cancer activities ( 6 , 7 ). They demonstrate minimal general toxicity and adverse side effects and thus may represent potential alternative medicine to conventional cytotoxic chemotherapy ( 8 , 9 ). Baicalin is a flavone glycoside found in Scutellaria baicalensis Georgi, with a chemical formula of C 21 H 18 O 11 ( 10 ).…”

Hypericum japonicum Thunb. ex Murray: Phytochemistry, Pharmacology, Quality Control and Pharmacokinetics of an Important Herbal Medicine

“…The extract of H. japonicum significantly inhibited the proliferation of CNE-2 cells and HepG2 cells in vitro by inducing cell cycle arrest, showing a dose-dependent response at the low concentrations of 25 mg/mL and 5 mg/mL, respectively [35,36,37]. Meanwhile, the aqueous extract of H. japonicum displayed a synergistic tumor-inhibiting effect with 5-FU in mice at 3, 6 and 12 g/kg/day, administered 24 h after the tumor inoculation, once daily for 10 days, indicting its usefulness in antitumor therapy [38]. Using a serum pharmacology method, BEL-7404 liver cancer cells were co-cultured with the collected serum containing four fraction of H. japonicum (ethanol extract, ethyl acetate extract, n -butanol extract and aqueous extract) at different dosage.…”

“…In addition, the extract showed strong effects on improving the immune function, reducing the toxic effect of 5-fluorouracil and prolonging the survival time in the tumor-bearing mice. Therefore, it was considered to have immunoregulatory activity [38].…”

Role of traditional medicines in the management of cancer

“…Hypericum japonicum Thunb. extract is reported to enhance the efficacy of 5-fluorouracil treatment in murine liver tumor xenografts and reduction of toxicity of chemotherapy in hepatoma H22-bearing mice [81]. Diarrhoea and nausea are common side effects of irinotecan, and ulceration and intestinal bleeding can occur following its administration as the drug causes cell death and inflammation in the intestine [82].…”