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Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis (Danggui) in human bladder cancer cells.
BMC Complement Altern Med. 2017 Dec 06; 17(1):523.BC

Abstract

BACKGROUND

N-butylidenephthalide (BP) isolated from Radix Angelica Sinensis (Danggui) exhibits anti-tumorigenic effect in various cancer cells both in vivo and in vitro. The effect of BP in bladder cancer treatment is still unclear and worth for further investigate.

METHODS

Changes of patients with bladder cancer after Angelica Sinensis exposure were evaluated by analysis of Taiwan's National Health Insurance Research Database (NHIRD) database. The anti-proliferative effect of BP on human bladder cancer cells was investigated and their cell cycle profiles after BP treatment were determined by flow cytometry. BP-induced apoptosis was demonstrated by Annexin V-FITC staining and TUNEL assay, while the expressions of apoptosis-related proteins were determined by western blot. The migration inhibitory effect of BP on human bladder cancer cells were shown by trans-well and wound healing assays. Tumor model in NOD-SCID mice were induced by injection of BFTC human bladder cancer cells.

RESULTS

The correlation of taking Angelica sinensis and the incidence of bladder cancer in NHIRD imply that this herbal product is worth for further investigation. BP caused bladder cancer cell death in a time- and dose- dependent manner and induced apoptosis via the activation of caspase-9 and caspase-3. BP also suppressed the migration of bladder cancer cells as revealed by the trans-well and wound healing assays. Up-regulation of E-cadherin and down-regulation of N-cadherin were evidenced by real-time RT-PCR analysis after BP treatment in vitro. Besides, in combination with BP, the sensitivity of these bladder cancer cells to cisplatin increased significantly. BP also suppressed BFTC xenograft tumor growth, and caused 44.2% reduction of tumor volume after treatment for 26 days.

CONCLUSIONS

BP caused bladder cancer cell death through activation of mitochondria-intrinsic pathway. BP also suppressed the migration and invasion of these cells, probably by modulating EMT-related genes. Furthermore, combination therapy of BP with a lower dose of cisplatin significantly inhibited the growth of these bladder cancer cell lines. The incidence of bladder cancer decreased in patients who were exposed to Angelica sinensis, suggesting that BP could serve as a potential adjuvant in bladder cancer therapy regimen.

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Authors+Show Affiliations

Chiu SC
Department of Research, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan. Department of Laboratory Medicine, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan. General Education Center, Tzu Chi University of Science and Technology, Hualien, Taiwan.
Chiu TL
Division of Neuro-Oncology, Neuro-Medical Scientific Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Huang SY
Department of Ophthalmology, Mackay Memorial Hospital, Hsinchu, Taiwan.
Chang SF
Department of Research, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taichung, Taiwan.
Chen SP
Tzu Chi Stem Cells Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan.
Pang CY
Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan. cypang@mail.tcu.edu.tw. Institute of Medical Sciences, School of Medicine, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 970, Taiwan. cypang@mail.tcu.edu.tw.
Hsieh TF
Department of Urology, Taichung Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Section 1, Fengxing Road, Tanzi Dist., Taichung City, 427, Taiwan. pchdf95@gmail.com. School of Medicine, Tzu Chi University, Hualien, Taiwan. pchdf95@gmail.com.

MeSH

AdultAngelica sinensisAnimalsAntineoplastic AgentsApoptosisCell Line, TumorCell MovementCell ProliferationFemaleHumansMaleMiceMice, Inbred NODMiddle AgedNeoplasm MetastasisPhthalic AnhydridesPlant ExtractsUrinary Bladder NeoplasmsXenograft Model Antitumor Assays

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29207978

Citation

Chiu, Sheng-Chun, et al. "Potential Therapeutic Effects of N-butylidenephthalide From Radix Angelica Sinensis (Danggui) in Human Bladder Cancer Cells." BMC Complementary and Alternative Medicine, vol. 17, no. 1, 2017, p. 523.
Chiu SC, Chiu TL, Huang SY, et al. Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis (Danggui) in human bladder cancer cells. BMC Complement Altern Med. 2017;17(1):523.
Chiu, S. C., Chiu, T. L., Huang, S. Y., Chang, S. F., Chen, S. P., Pang, C. Y., & Hsieh, T. F. (2017). Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis (Danggui) in human bladder cancer cells. BMC Complementary and Alternative Medicine, 17(1), 523. https://doi.org/10.1186/s12906-017-2034-3
Chiu SC, et al. Potential Therapeutic Effects of N-butylidenephthalide From Radix Angelica Sinensis (Danggui) in Human Bladder Cancer Cells. BMC Complement Altern Med. 2017 Dec 6;17(1):523. PubMed PMID: 29207978.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Potential therapeutic effects of N-butylidenephthalide from Radix Angelica Sinensis (Danggui) in human bladder cancer cells. AU - Chiu,Sheng-Chun, AU - Chiu,Tsung-Lang, AU - Huang,Sung-Ying, AU - Chang,Shu-Fang, AU - Chen,Shee-Ping, AU - Pang,Cheng-Yoong, AU - Hsieh,Teng-Fu, Y1 - 2017/12/06/ PY - 2017/02/16/received PY - 2017/11/28/accepted PY - 2017/12/7/entrez PY - 2017/12/7/pubmed PY - 2017/12/28/medline KW - Apoptosis KW - Bladder cancer KW - Combination therapy KW - Metastasis KW - NHIRD KW - n-butylidenephthalide SP - 523 EP - 523 JF - BMC complementary and alternative medicine JO - BMC Complement Altern Med VL - 17 IS - 1 N2 - BACKGROUND: N-butylidenephthalide (BP) isolated from Radix Angelica Sinensis (Danggui) exhibits anti-tumorigenic effect in various cancer cells both in vivo and in vitro. The effect of BP in bladder cancer treatment is still unclear and worth for further investigate. METHODS: Changes of patients with bladder cancer after Angelica Sinensis exposure were evaluated by analysis of Taiwan's National Health Insurance Research Database (NHIRD) database. The anti-proliferative effect of BP on human bladder cancer cells was investigated and their cell cycle profiles after BP treatment were determined by flow cytometry. BP-induced apoptosis was demonstrated by Annexin V-FITC staining and TUNEL assay, while the expressions of apoptosis-related proteins were determined by western blot. The migration inhibitory effect of BP on human bladder cancer cells were shown by trans-well and wound healing assays. Tumor model in NOD-SCID mice were induced by injection of BFTC human bladder cancer cells. RESULTS: The correlation of taking Angelica sinensis and the incidence of bladder cancer in NHIRD imply that this herbal product is worth for further investigation. BP caused bladder cancer cell death in a time- and dose- dependent manner and induced apoptosis via the activation of caspase-9 and caspase-3. BP also suppressed the migration of bladder cancer cells as revealed by the trans-well and wound healing assays. Up-regulation of E-cadherin and down-regulation of N-cadherin were evidenced by real-time RT-PCR analysis after BP treatment in vitro. Besides, in combination with BP, the sensitivity of these bladder cancer cells to cisplatin increased significantly. BP also suppressed BFTC xenograft tumor growth, and caused 44.2% reduction of tumor volume after treatment for 26 days. CONCLUSIONS: BP caused bladder cancer cell death through activation of mitochondria-intrinsic pathway. BP also suppressed the migration and invasion of these cells, probably by modulating EMT-related genes. Furthermore, combination therapy of BP with a lower dose of cisplatin significantly inhibited the growth of these bladder cancer cell lines. The incidence of bladder cancer decreased in patients who were exposed to Angelica sinensis, suggesting that BP could serve as a potential adjuvant in bladder cancer therapy regimen. SN - 1472-6882 UR - https://www.unboundmedicine.com/medline/citation/29207978/Potential_therapeutic_effects_of_N_butylidenephthalide_from_Radix_Angelica_Sinensis__Danggui__in_human_bladder_cancer_cells_ DB - PRIME DP - Unbound Medicine ER -