title: Deltonin induces apoptosis in MDA‑MB‑231 human breast cancer cells via             reactive oxygen species‑mediated mitochondrial dysfunction and ERK/AKT signaling             pathways.
abstract: Deltonin, a steroidal saponin isolated from Dioscorea zingiberensis Wright,             exhibits high cytotoxic activity in cancer cells. In the present study, the effects             of deltonin on cell proliferation and apoptosis were evaluated in the MDA‑MB‑231             human breast carcinoma cell line. Following treatment with deltonin, the viability             of MDA‑MB‑231 cells was analyzed using MTT assay and apoptosis, mitochondrial             membrane potential (∆Ψm) alternation and intracellular reactive oxygen species             (ROS) generation was determined by flow cytometry. In addition, western blot analysis             was performed to examine the expression of apoptosis‑associated proteins. The             results demonstrated that deltonin induced apoptosis in MDA‑MB‑231 cells in a             time‑ and concentration‑dependent manner. Apoptosis was associated with depolarization             of ∆Ψm and time‑dependent ROS generation. Deltonin treatment also resulted in             Bax upregulation, Bcl-2 downregulation, activation of caspase‑3 and ‑8 and poly             (ADP ribose) polymerase cleavage. Decreased levels of phosphorylated extracellular             signal‑regulated kinase (ERK) and phosphorylated AKT were also observed. Results             indicate that the proliferation inhibitory effect of deltonin is associated with             its apoptosis‑inducing effect, which may correlate with ROS‑mediated mitochondrial             dysfunction as well as activation of the ERK/AKT signaling pathways. Therefore,             deltonin may be a potential chemotherapeutic agent for the treatment of breast             cancer.
authors: Laboratory of Ethnopharmacology, Regenerative Medicine Research Center, Institute for Nanobiomedical Technology and Membrane Biology, West China Hospital/Medical School, Sichuan University, Sichuan 610041, PR China.
authors: Shiyuan
authors: S
authors: Zhang
authors: Yang
authors: Y
authors: He
authors: Qingyi
authors: Q
authors: Tong
authors: Qianming
authors: Q
authors: Chen
authors: Xiaohua
authors: X
authors: Wu
authors: Wen
authors: W
authors: Huang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D027742:Dioscorea / Q000737:chemistry; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013150:Spirostans / Q000737:chemistry / Q000633:toxicity*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D013150:Spirostans; D051028:bcl-2-Associated X Protein; C016347:deltonin; D011065:Poly(ADP-ribose) Polymerases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D053148:Caspase 3; D053181:Caspase 8