title: Reduced expression of HSP27 following HAD-B treatment is associated with Her2 downregulation in NIH:OVCAR-3 human ovarian cancer cells.
abstract: The Korean traditional medicine, HangAmDan (HAD), was developed in 1996 for use as an antitumor agent, and has since been modified to HAD‑B (an altered form of HAD), in order to potentiate its therapeutic effects. In the present study, the effect of HAD‑B on the proliferation and invasion of NIH:OVCAR‑3 and SKOV‑3 human ovarian cancer cell lines was investigated. In addition, the expression of major signal transduction molecules and changes in the proteome in these cells were measured. HAD‑B treatment effectively induced a reduction in the levels of cell proliferation in serum‑free conditioned media. However, unaltered levels of PARP and caspase‑3 indicated that HAD‑B does not reduce proliferation by inducing apoptotic cell death. Fluorescence‑activated cell sorting analysis revealed no significant change in apoptosis following HAD-B treatment. Invasion assay results indicated a reduced rate of invasion following HAD‑B treatment. HAD‑B also influenced the expression of major signal transduction molecules; the phosphorylation of mTOR and AKT was reduced, while that of ERK was increased. Alterations in the proteomes of the two cell lines were investigated following HAD‑B treatment. Among the 9 proteins with differential expression, heat‑shock protein β‑1 (HSP27) was downregulated in NIH:OVCAR‑3 cells treated with HAD‑B. The reduced expression of HSP27 was associated with human epidermal growth factor receptor 2 (Her2) downregulation in these cells. In conclusion, the results of the current proteome assessment suggest that HAD‑B has the potential to suppress the proliferation and invasion of human ovarian cancer cells. HAD‑B treatment of NIH:OVCAR‑3 cells suppressed HSP27 expression and was also associated with Her2 downregulation.
authors.affiliation: East-West Cancer Center, College of Korean Medicine, Daejeon University, Daejeon 302-869, Republic of Korea.
authors.forename: Kuo Chu
authors.initials: KC
authors.lastname: Li
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Kyun
authors.initials: K
authors.lastname: Heo
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Nitin
authors.initials: N
authors.lastname: Ambade
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Min Kyung
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Kyung-Hee
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Research Institute, National Cancer Center, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
authors.forename: Byong Chul
authors.initials: BC
authors.lastname: Yoo
authors.affiliation: East-West Cancer Center, College of Korean Medicine, Daejeon University, Daejeon 302-869, Republic of Korea.
authors.forename: Hwa-Seung
authors.initials: HS
authors.lastname: Yoo
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis / Q000378:metabolism*; D006360:Heat-Shock Proteins; D006801:Humans; D055670:Medicine, Korean Traditional; D018832:Molecular Chaperones; D009361:Neoplasm Invasiveness / Q000473:pathology; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010053:Ovary / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D020543:Proteome / Q000032:analysis / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D020543:Proteome; D018719:Erb-b2 Receptor Tyrosine Kinases; C057725:HSPB1 protein, human