title: Activation of p53 signaling and inhibition of androgen receptor mediate tanshinone IIA induced G1 arrest in LNCaP prostate cancer cells.
abstract: Our group previously reported that tanshinone IIA induced apoptosis via a mitochondria dependent pathway in LNCaP prostate cancer cells. In the present study, the roles of androgen receptor (AR) and p53 signaling pathways were investigated in tanshinone IIA-induced G1 arrest in LNCaP cells. Tanshinone IIA significantly inhibited the growth and proliferation of LNCaP cells by colony formation and BrdU incorporation assays, respectively. Tanshinone IIA induced cell cycle arrest at G1 phase and down-regulated cyclin D1, CDK2 and CDK4. Furthermore, tanshinone IIA activated the phosphorylation of p53 at Ser 15 residue and its downstream p21 and p27. Additionally, tanshinone IIA suppressed the expression of AR and prostate specific antigen (PSA). Conversely, silencing p53 using its specific siRNA reversed cyclin D1 expression inhibited by tanshinone IIA. However, knockdown of AR had no effect on the p53/p21/p27 signaling pathway activated by tanshinone IIA in LNCaP cells. In AR siRNA-transfected cells, tanshinone IIA did not cause cell cycle arrest and reduce cyclin D1, implying that AR is essential to induce G1 arrest by tanshinone IIA in LNCaP cells. Taken together, the findings suggest that tanshinone IIA induces G1 arrest via activation of p53 signaling and inhibition of AR in LNCaP cells.
authors: College of Oriental Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea.
authors: Suk-Hyun
authors: SH
authors: Won
authors: Hyo-Jeong
authors: HJ
authors: Lee
authors: Soo-Jin
authors: SJ
authors: Jeong
authors: Junxuan
authors: J
authors: Lü
authors: Sung-Hoon
authors: SH
authors: Kim
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D059002:Androgen Receptor Antagonists / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D008297:Male; D018517:Plant Roots / Q000737:chemistry; D011467:Prostate / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D034741:RNA, Small Interfering; D011944:Receptors, Androgen / Q000187:drug effects* / Q000378:metabolism; D027561:Salvia miltiorrhiza / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000378:metabolism
chemical_list: C410798:AR protein, human; D045784:Abietanes; D059002:Androgen Receptor Antagonists; D000972:Antineoplastic Agents, Phytogenic; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D016159:Tumor Suppressor Protein p53; C021751:tanshinone