Natural Plant Extract Tubeimoside I Promotes Apoptosis-Mediated Cell Death in Cultured Human Hepatoma (HepG2) Cells

Abstract

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

Traditional Chinese medicine for prevention and treatment of hepatocarcinoma: From bench to bedside

“…TianNanXing (Arisaema heterophyllum) may activate caspase3 and induce apoptosis in hepatocarcinoma cells [121] . Tubeimoside Ⅰ, an ingredient from TuBeiMu (Bolbostemma paniculatum), could upregulate Bax/ Bcl2 and induce intrinsic apoptosis in hepatoma cells [122] . Toxic Chinese herb or components such as QuanXie (scorpio), Norcantharidin and polypeptides from bee venom are potent to induce apoptosis in liver cancer cells [123125] .…”

Lithium Causes G2 Arrest of Renal Principal Cells

“…26 These data are consistent with cells arrested in the G2 phase because an altered nuclear morphology in G2-arrested cells was previously documented. [30][31][32] The consequences of such a prolonged G2 cell cycle arrest are not fully understood, although recent investigations of different AKI models indicate that activation of c-Jun NH 2 -terminal signaling in G2-arrested cells can lead to renal fibrosis due to the upregulation of profibrotic cytokines, including TGF-b1. 24 Because fibrosis and CKD are also observed after long-term lithium treatment, 33 and lithium has been shown to activate c-Jun NH 2 -terminal signaling 16 and stimulate TGF-b1 production in the collecting duct, 33 the role of G2-arrested cells in lithium-induced fibrosis should be further investigated.…”

In vitro study on the antitumor activity of several new polyoxometalates

“…Among them , Wo had the minimum IC 50 for human tumor cells.The change of Bcl-2 family molecules Bax and Bim indicated POM Wo may interfere the stability of mitochondria. Mitochondria act as the energy factory and a senser the receive oxadation-reduction change in a cell [12,13]. So the present results afford new clues for the mechanism for antitumor POM.…”