Hepatoma is one of the most prevalent malignant tumor types and the third leading cause of cancer-related death worldwide.1) Each year, approximately 550000 new cases of hepatoma are reported worldwide, representing more than 5% of all human cancers.2) The incidence is particularly high among Eastern Asian and African regions, 3) but also rapidly rising in other parts of the world such as the United States. 4)Despite the development and use of multimodality therapies including chemotherapy, the clinical outcome of hepatoma treatment remains unsatisfactory, with usually less than 7% of the 5-year overall survival rate, 5,6) This may be in part due to ineffectiveness of the currently available chemotherapeutic drugs. Therefore, novel effective chemotherapeutic agents are desired, particularly those derived from natural products because of their intrinsic advantages. 7,8) One such agent is tubeimoside I (TBMS I), a constituent isolated from tuber of Bolbostemma paniculatum (MAXIM.) FRANQUET (Cucurbitaceae) that has long been used as a traditional Chinese herbal medicine to treat a wide variety of illnesses including inflammation and snake venom. 9) In the early 1980's, TBMS I was isolated and identified as a triterpenoid saponin with a unique macrocyclic structure as shown in Fig. 1. 10,11) Subsequently, it has been shown that TBMS I could be a potent anti-tumor agent 12) by inducing apoptosis in a variety of human cancer cell lines including promyelocytic leukemia (HL-60) cells, 13) cervical cancer (HeLa) cells, 14) and nasopharyngeal carcinoma (CNE-2Z) cells.15) However, TBMS I so far has not been well studied for its anti-tumor activity against hepatoma, even though that TBMS I is known to preferentially distribute in the liver during in vivo metabolism, and thus might better target liver cancer, or hepatoma. 16)Therefore, we evaluated TBMS I for its cytotoxicity to cultured human hepatoma cells or normal liver cells, from HepG2 or L-02 cell lines, respectively. We also investigated apoptosis-associated molecular events as potential mechanisms responsible for the cytotoxic effect of TBMS I on HepG2 cells. We found that compared to normal L-02 cells, TBMS I could inhibit proliferation of HepG2 cells more potently, which was paralleled by induction of several important signaling pathways associated with apoptosis, suggesting that TBMS I may be a potent promoter of apoptosis-mediated cell death in HepG2 cells and thus a particularly good candidate
Abstract. Tubeimoside I (TBMS I) is a natural compound extracted from Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae), a traditional Chinese herbal medicine widely used for the treatment of inflammation. Recently, it has been suggested that TBMS I may be a potent anticancer agent for a variety of human cancers. However, TBMS I is known to distribute preferentially in the liver, and thus may harm normal liver cells if it is delivered systemically for cancer treatment. This safety concern warrants careful evaluation of the hepatotoxicity of TBMS I to normal liver cells, which to date has not been carried out. Here, we report the cytotoxic effects of TBMS I on one type of normal liver cells (L-02 cells), and the associated molecular events as underlying mechanisms. Cultured human normal liver L-02 cells were treated with TBMS I at concentrations of 0, 15 and 30 µM for 24, 48 and 72 h, respectively. Subsequently, the cell survival rate was evaluated by the MTT dye method, and several key molecular events associated with apoptosis were assayed, including mitochondrial depolarization, release of cytochrome c (cytc), activation of caspases, and the balance between Bax and Bcl-2 protein expression. Our results indicate that TBMS I inhibited the proliferation of L-02 cells in a dose-and timedependent manner. The TBMS I-induced growth inhibition of L-02 cells was accompanied by the collapse of mitochondrial membrane potential, release of cyt-c from the mitochondria to the cytosol, activation of caspase-9 and -3, decrease of anti-apoptotic protein Bcl-2 levels and increase of the pro-apoptotic protein Bax levels, all indicative of apoptosis through the mitochondrial pathway. Taken together, these results confirm that TBMS I has a significant apoptotic effect on normal liver L-02 cells, which may be significant to its clinical applications. IntroductionTubeimoside (TBMS), or the tuber of Bolbostemma paniculatum (Maxim.) Franquet (Cucurbitaceae), is a herb that has long been used in traditional Chinese medicine, and was listed in the Supplement to the Compendium of Materia Medica published in early 1765 (1). TBMS is most widely used for the treatment of illnesses, such as inflammation and snake venoms, but it has also been reported to show potent antitumor activity (2). Such antitumor activity in part motivated the successful isolation of TBMS I, a triterpenoid saponin whose chemical structure is shown in Fig. 1 (3,4). Subsequent studies confirmed that TBMS I inhibits the growth of cultured cancer cells of several human cancer cell lines, including the human promyelocytic leukemia (HL-60), nasopharyngeal carcinoma CNE-2Z (CNE-2Z) and HeLa cell lines (5). These studies suggest that TBMS I is be a candidate novel antitumor drug, despite its side effects on the digestive system causing nausea and vomiting (6). Furthermore, at the molecular level, the TBMS I-induced growth inhibition of cancer cells may well be mediated through apoptosis-associated processes, including microtubule depolymerization (7), prolonged endopl...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.