Tags

Type your tag names separated by a space and hit enter

Triacanthine exerts antitumor effects on bladder cancer in vitro and in vivo.
Phytomedicine 2019; 64:153069P

Abstract

BACKGROUND

Numerous studies have focused on solvent extracts from locust trees (Gleditsia spp.), which contain diverse bioactive components including saponins, flavonoids, and alkaloids. However, because of the undefined nature of such phytochemicals, their clinical application as chemotherapeutic agents has often been limited.

PURPOSE

This study aimed to evaluate the anti-oncogenic activity of triacanthine, an alkaloid obtained from Gleditsia triacanthos L.

STUDY DESIGN

The anti-oncogenicity of triacanthine in vitro was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell-counting kit-8 assay (CCK-8 assay), flow cytometry, imunoblot, migration and invasion assays, zymography, and electrophoretic mobility shift assay in the human bladder carcinoma cell line EJ. The in vivo efficacy of triacanthine was evaluated via oral administration to EJ-xenografted BALB/c nude mice. To identify the side effects of triacanthine, cisplatin was also administered and an acute toxicity test was performed.

RESULTS

Triacanthine significantly inhibited EJ cell proliferation (IC50 600 µM). Flow cytometry analysis revealed that cells were arrested in the G1 phase, and apoptotic cells accumulated in sub-G1 phase in a dose-dependent manner. Triacanthine inhibited the G1-S transition by deterring complex formation between cyclin-dependent kinases and cyclins, thereby up-regulating cell cycle inhibitors p21WAF1 and p27KIP1. In addition, triacanthine induced a caspase-dependent extrinsic pathway of apoptosis and autophagy. Early responsive kinases, extracellular signal-regulated kinase (ERK) and Janus kinase (JNK) were up-regulated by triacanthine. Triacanthine-mediated inhibition of the migratory and invasive potential of EJ cells was attributed to reduction of matrix metalloproteinase (MMP)-9 due to suppression of binding activities of the transcription factors activator protein (AP)-1, specificity protein (Sp)-1, and nuclear factor (NF)-κB. In an in vivo study, triacanthine significantly limited growth of xenografted tumors. Interestingly, while cisplatin resulted in significant weight loss after a 5-mg/kg dose, triacanthine did not cause weight loss, behavioral abnormalities, altered biochemical parameters, or tissue staining. A single oral dose acute-toxicity test (triacanthine 2,000 mg/kg) produced no adverse cytotoxic effects via blood biochemical tests and tissue-organ staining.

CONCLUSION

To our knowledge, this is the first systematic evaluation of the anti-oncogenic activity of triacanthine. Therefore, we believe that our findings may guide the development of novel chemotherapeutic agents for bladder cancers.

Authors+Show Affiliations

Department of Food Science and Nutrition, Jeju National University, Jeju 63243, Republic of Korea.Department of Food and Nutrition, Chung-Ang University, Anseong 17546, Republic of Korea.Department of Food and Nutrition, Chung-Ang University, Anseong 17546, Republic of Korea.Department of Food and Nutrition, Chung-Ang University, Anseong 17546, Republic of Korea.Department of Plant Science and Technology, Chung-Ang University, Anseong 17546, Republic of Korea.Department of Food Science and Nutrition, Jeju National University, Jeju 63243, Republic of Korea.Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea.Department of Urology, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.Department of Food and Nutrition, Chung-Ang University, Anseong 17546, Republic of Korea. Electronic address: sumoon66@cau.ac.kr.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31421400

Citation

Shin, Seung-Shick, et al. "Triacanthine Exerts Antitumor Effects On Bladder Cancer in Vitro and in Vivo." Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, vol. 64, 2019, p. 153069.
Shin SS, Park YJ, Hwang B, et al. Triacanthine exerts antitumor effects on bladder cancer in vitro and in vivo. Phytomedicine. 2019;64:153069.
Shin, S. S., Park, Y. J., Hwang, B., Park, S. L., Han, S. W., Park, S. S., ... Moon, S. K. (2019). Triacanthine exerts antitumor effects on bladder cancer in vitro and in vivo. Phytomedicine : International Journal of Phytotherapy and Phytopharmacology, 64, p. 153069. doi:10.1016/j.phymed.2019.153069.
Shin SS, et al. Triacanthine Exerts Antitumor Effects On Bladder Cancer in Vitro and in Vivo. Phytomedicine. 2019 Aug 9;64:153069. PubMed PMID: 31421400.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Triacanthine exerts antitumor effects on bladder cancer in vitro and in vivo. AU - Shin,Seung-Shick, AU - Park,Yu-Jin, AU - Hwang,Byungdoo, AU - Park,Sung Lyea, AU - Han,Sang-Wook, AU - Park,Sung-Soo, AU - Choi,Yung Hyun, AU - Kim,Wun-Jae, AU - Moon,Sung-Kwon, Y1 - 2019/08/09/ PY - 2018/06/12/received PY - 2019/08/07/revised PY - 2019/08/09/accepted PY - 2019/8/20/pubmed PY - 2019/8/20/medline PY - 2019/8/18/entrez KW - Bladder cancer KW - Invasion KW - Migration KW - Proliferation KW - Triacanthine KW - Xenograft SP - 153069 EP - 153069 JF - Phytomedicine : international journal of phytotherapy and phytopharmacology JO - Phytomedicine VL - 64 N2 - BACKGROUND: Numerous studies have focused on solvent extracts from locust trees (Gleditsia spp.), which contain diverse bioactive components including saponins, flavonoids, and alkaloids. However, because of the undefined nature of such phytochemicals, their clinical application as chemotherapeutic agents has often been limited. PURPOSE: This study aimed to evaluate the anti-oncogenic activity of triacanthine, an alkaloid obtained from Gleditsia triacanthos L. STUDY DESIGN: The anti-oncogenicity of triacanthine in vitro was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, cell-counting kit-8 assay (CCK-8 assay), flow cytometry, imunoblot, migration and invasion assays, zymography, and electrophoretic mobility shift assay in the human bladder carcinoma cell line EJ. The in vivo efficacy of triacanthine was evaluated via oral administration to EJ-xenografted BALB/c nude mice. To identify the side effects of triacanthine, cisplatin was also administered and an acute toxicity test was performed. RESULTS: Triacanthine significantly inhibited EJ cell proliferation (IC50 600 µM). Flow cytometry analysis revealed that cells were arrested in the G1 phase, and apoptotic cells accumulated in sub-G1 phase in a dose-dependent manner. Triacanthine inhibited the G1-S transition by deterring complex formation between cyclin-dependent kinases and cyclins, thereby up-regulating cell cycle inhibitors p21WAF1 and p27KIP1. In addition, triacanthine induced a caspase-dependent extrinsic pathway of apoptosis and autophagy. Early responsive kinases, extracellular signal-regulated kinase (ERK) and Janus kinase (JNK) were up-regulated by triacanthine. Triacanthine-mediated inhibition of the migratory and invasive potential of EJ cells was attributed to reduction of matrix metalloproteinase (MMP)-9 due to suppression of binding activities of the transcription factors activator protein (AP)-1, specificity protein (Sp)-1, and nuclear factor (NF)-κB. In an in vivo study, triacanthine significantly limited growth of xenografted tumors. Interestingly, while cisplatin resulted in significant weight loss after a 5-mg/kg dose, triacanthine did not cause weight loss, behavioral abnormalities, altered biochemical parameters, or tissue staining. A single oral dose acute-toxicity test (triacanthine 2,000 mg/kg) produced no adverse cytotoxic effects via blood biochemical tests and tissue-organ staining. CONCLUSION: To our knowledge, this is the first systematic evaluation of the anti-oncogenic activity of triacanthine. Therefore, we believe that our findings may guide the development of novel chemotherapeutic agents for bladder cancers. SN - 1618-095X UR - https://www.unboundmedicine.com/medline/citation/31421400/Triacanthine_exerts_antitumor_effects_on_bladder_cancer_in_vitro_and_in_vivo L2 - https://linkinghub.elsevier.com/retrieve/pii/S0944-7113(19)30234-X DB - PRIME DP - Unbound Medicine ER -