title: Cytotoxic effects of kazinol A derived from Broussonetia papyrifera on human bladder cancer cells, T24 and T24R2.
abstract: BACKGROUND
  Broussonetia papyrifera (B. papyrifera), also known as paper mulberry, has been used as a traditional medicine for the treatment of several diseases, including ophthalmic disorders and impotency. However, the biological activity of kazinol A (1) among flavonols isolated from B. papyrifera has not been identified.
  
  
  OBJECTIVE
  We identified a candidate metabolite for anti-human bladder cancer treatment from B. papyrifera and investigated the possible molecular mechanisms underlying its cytotoxic effects in T24 and cisplatin-resistant T24R2 human bladder cancer cells.
  
  
  METHODS
  T24 and T24R2 cells were treated with five flavonols from B. papyrifera and their cytotoxic effects were determined using MTT assay, cell cycle analysis, mitochondrial membrane potential, and propidium iodide staining. Autophagy rate was calculated by counting LC3-GFP dots in the cells. All related protein expressions were analyzed by immunoblotting.
  
  
  RESULTS
  Compound 1 showed relatively higher cytotoxicity in the human bladder cancer cells, T24 and T24R2, rather than other tissues-originated cancer cells. Compound 1 significantly attenuated cell growth through G0/1arrest mediated by a decrease in cyclin D1 and an increase of p21. Apoptosis and autophagy induced by compound 1 treatment was accompanied by a modulation of the AKT-BAD pathway and AMPK-mTOR pathway, respectively.
  
  
  CONCLUSIONS
  Our results suggest that compound 1 induces cytotoxic effects in human bladder cancer cells, including the cisplatin-resistant T24R2. Compound 1 may be a candidate for the development of effective anti-cancer drug on human urinary bladder cancer.
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Soojong
authors.initials: S
authors.lastname: Park
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Fudhaili
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Sang-Seok
authors.initials: SS
authors.lastname: Oh
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Ki Won
authors.initials: KW
authors.lastname: Lee
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Hamadi
authors.initials: H
authors.lastname: Madhi
authors.affiliation: Department of Orthopaedic Surgery, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Dong-Hee
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Jiyun
authors.initials: J
authors.lastname: Yoo
authors.affiliation: Natural Medicine Research Center, KRIBB, 30-Yeongudanji-ro, Ochang-eup, Cheongwon 363-883, Republic of Korea.
authors.forename: Hyung Won
authors.initials: HW
authors.lastname: Ryu
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Republic of Korea.
authors.forename: Ki-Hun
authors.initials: KH
authors.lastname: Park
authors.affiliation: Division of Applied Life Science (BK21 Plus), Gyeongsang National University, Jinju, Republic of Korea; PMBBRC, Gyeongsang National University, Jinju, Republic of Korea. Electronic address: kdkim88@gnu.ac.kr.
authors.forename: Kwang Dong
authors.initials: KD
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D031623:Broussonetia / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D001743:Urinary Bladder / Q000187:drug effects* / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D002945:Cisplatin
keywords: Broussonetia papyrifera; Cancer drug; Kazinol A; Urinary bladder cancer