Skip to main content
Top
Published in: BMC Complementary Medicine and Therapies 1/2019

Open Access 01-12-2019 | NSCLC | Research article

Jingfukang induces anti-cancer activity through oxidative stress-mediated DNA damage in circulating human lung cancer cells

Authors: Zujun Que, Zhiyi Zhou, Bin Luo, Changsheng Dong, Yi Jiang, Hegen Li, Jianhui Tian

Published in: BMC Complementary Medicine and Therapies | Issue 1/2019

Login to get access

Abstract

Background

Metastasis is the main cause of lung cancer death. As a seed of metastasis, circulating tumor cells are an important target for metastasis intervention. The traditional Chinese medicine, Jinfukang, has been clinically available for the treatment of non-small cell lung cancer (NSCLC). In this study, we investigated the action and underlying mechanisms of Jinfukang against circulating lung tumor cells.

Methods

The cell counting kit-8 (CCK-8), colony formation and cell cycle assays were used to study the cell proliferation ability. Flow cytometry was used to detect the apoptosis and the expression level of ROS and Caspase-3. Comet and TUNEL assays were used to detect DNA damage. DNA damage related pathway protein was detected by western blot.

Results

Jinfukang significantly inhibits the proliferation of CTC-TJH-01 cells by inducing G1 phase arrest and inhibits their colony formation in a dose-dependent manner. Moreover, Jinfukang induces apoptosis in CTC-TJH-01 cells through the ROS-mediated ATM/ATR-p53 pathway and DNA damage.

Conclusions

Our findings suggest that Jinfukang may be a potential drug for lung cancer metastasis.
Appendix
Available only for authorised users
Literature
1.
go back to reference Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, Bonaventure A, Valkov M, Johnson CJ, Esteve J, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023–75.CrossRef Allemani C, Matsuda T, Di Carlo V, Harewood R, Matz M, Niksic M, Bonaventure A, Valkov M, Johnson CJ, Esteve J, et al. Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries. Lancet. 2018;391(10125):1023–75.CrossRef
2.
go back to reference Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, De WM. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919.CrossRef Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, Yokoi T, Chiappori A, Lee KH, De WM. Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer. N Engl J Med. 2017;377(20):1919.CrossRef
3.
go back to reference Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Jr CW, Wu YL, Paz-Ares L. Lung cancer: current therapies and new targeted treatments. Lancet. 2016;389(10066):299.CrossRef Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Jr CW, Wu YL, Paz-Ares L. Lung cancer: current therapies and new targeted treatments. Lancet. 2016;389(10066):299.CrossRef
4.
go back to reference Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017. https://doi.org/10.1016/S1470-2045(17)30608-3.CrossRef Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017. https://​doi.​org/​10.​1016/​S1470-2045(17)30608-3.CrossRef
5.
go back to reference Vansteenkiste JF, Cho BC, Vanakesa T, De Pas T, Zielinski M, Kim MS, Jassem J, Yoshimura M, Dahabreh J, Nakayama H, et al. Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(6):822–35.CrossRef Vansteenkiste JF, Cho BC, Vanakesa T, De Pas T, Zielinski M, Kim MS, Jassem J, Yoshimura M, Dahabreh J, Nakayama H, et al. Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(6):822–35.CrossRef
6.
go back to reference Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018;391(10124):933.CrossRef Moslehi JJ, Salem JE, Sosman JA, Lebrun-Vignes B, Johnson DB. Increased reporting of fatal immune checkpoint inhibitor-associated myocarditis. Lancet. 2018;391(10124):933.CrossRef
7.
go back to reference Weber GF. Why does cancer therapy lack effective anti-metastasis drugs? Cancer Lett. 2013;328(2):207–11.CrossRef Weber GF. Why does cancer therapy lack effective anti-metastasis drugs? Cancer Lett. 2013;328(2):207–11.CrossRef
8.
go back to reference Syrigos K, Fiste O, Charpidou A, Grapsa D. Circulating tumor cells count as a predictor of survival in lung cancer. Crit Rev Oncol Hematol. 2018;125:60–8.CrossRef Syrigos K, Fiste O, Charpidou A, Grapsa D. Circulating tumor cells count as a predictor of survival in lung cancer. Crit Rev Oncol Hematol. 2018;125:60–8.CrossRef
9.
go back to reference Giuliano AE, Edge SB, Hortobagyi GN. Eighth edition of the AJCC cancer staging manual: breast cancer. Ann Surg Oncol. 2018;25(7):1–3.CrossRef Giuliano AE, Edge SB, Hortobagyi GN. Eighth edition of the AJCC cancer staging manual: breast cancer. Ann Surg Oncol. 2018;25(7):1–3.CrossRef
10.
go back to reference Lee SB, Sohn G, Kim J, Chung IY, Lee JW, Kim HJ, Ko BS, Son BH, Ahn SH. A retrospective prognostic evaluation analysis using the 8th edition of the American joint committee on cancer staging system for breast cancer. Breast Cancer Res Treat. 2018;23(8):1–10. Lee SB, Sohn G, Kim J, Chung IY, Lee JW, Kim HJ, Ko BS, Son BH, Ahn SH. A retrospective prognostic evaluation analysis using the 8th edition of the American joint committee on cancer staging system for breast cancer. Breast Cancer Res Treat. 2018;23(8):1–10.
11.
go back to reference Hashimoto M, Tanaka F, Yoneda K, Takuwa T, Matsumoto S, Okumura Y, Kondo N, Tsujimura T, Nakano T, Hasegawa S. Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer. J Thorac Dis. 2018;10(1):298–306.CrossRef Hashimoto M, Tanaka F, Yoneda K, Takuwa T, Matsumoto S, Okumura Y, Kondo N, Tsujimura T, Nakano T, Hasegawa S. Positive correlation between postoperative tumor recurrence and changes in circulating tumor cell counts in pulmonary venous blood (pvCTC) during surgical manipulation in non-small cell lung cancer. J Thorac Dis. 2018;10(1):298–306.CrossRef
12.
go back to reference Liu J, Shi Z, Li H, Xu Z, Zhu Y, Zhao L, Hong G, Liu L, Zhu H, Hui Z. Clinical observation on 271 cases of non-small cell lung cancer treated with yifei kangliu yin. 中国结合医学杂志:英文版. 2001;7(4):247–50. Liu J, Shi Z, Li H, Xu Z, Zhu Y, Zhao L, Hong G, Liu L, Zhu H, Hui Z. Clinical observation on 271 cases of non-small cell lung cancer treated with yifei kangliu yin. 中国结合医学杂志:英文版. 2001;7(4):247–50.
13.
go back to reference Jiao L, Wang Y, Ling X, Ming Y. Lung cancer prevention and therapy using the JinFuKang herbal mixture. Curr Pharmacol Rep. 2015;1(5):346–53.CrossRef Jiao L, Wang Y, Ling X, Ming Y. Lung cancer prevention and therapy using the JinFuKang herbal mixture. Curr Pharmacol Rep. 2015;1(5):346–53.CrossRef
14.
go back to reference Wang Z, Wu W, Wang Z, Tang Y, Deng Y, Xu L, Tian J, Shi Q. Ex vivo expansion of circulating lung tumor cells based on one-step microfluidics-based immunomagnetic isolation. Analyst. 2016;141(12):3621–5.CrossRef Wang Z, Wu W, Wang Z, Tang Y, Deng Y, Xu L, Tian J, Shi Q. Ex vivo expansion of circulating lung tumor cells based on one-step microfluidics-based immunomagnetic isolation. Analyst. 2016;141(12):3621–5.CrossRef
15.
go back to reference Zheng Y, Tian J. Development of rapid and highly sensitive HSPA1A promoter-driven;luciferase reporter system for assessing oxidative stress associated;with low-dose photodynamic therapy. Cell Stress Chaperones. 2013;18(2):203–13.CrossRef Zheng Y, Tian J. Development of rapid and highly sensitive HSPA1A promoter-driven;luciferase reporter system for assessing oxidative stress associated;with low-dose photodynamic therapy. Cell Stress Chaperones. 2013;18(2):203–13.CrossRef
16.
go back to reference Jiang ST, Han SY, Pang LN, Jiao YN, He XR, Li PP. Bu-Fei decoction and modified Bu-Fei decoction inhibit the growth of non-small cell lung cancer, possibly via inhibition of apurinic/apyrimidinic endonuclease 1. Int J Mol Med. 2018;41(4):2128–38.PubMedPubMedCentral Jiang ST, Han SY, Pang LN, Jiao YN, He XR, Li PP. Bu-Fei decoction and modified Bu-Fei decoction inhibit the growth of non-small cell lung cancer, possibly via inhibition of apurinic/apyrimidinic endonuclease 1. Int J Mol Med. 2018;41(4):2128–38.PubMedPubMedCentral
17.
go back to reference Que Z, Zou F, Zhang A, Zheng Y, Bi L, Zhong J, Tian J, Liu J. Ganoderic acid Me induces the apoptosis of competent T cells and increases the proportion of Treg cells through enhancing the expression and activation of indoleamine 2,3-dioxygenase in mouse lewis lung cancer cells. Int Immunopharmacol. 2014;23(1):192–204.CrossRef Que Z, Zou F, Zhang A, Zheng Y, Bi L, Zhong J, Tian J, Liu J. Ganoderic acid Me induces the apoptosis of competent T cells and increases the proportion of Treg cells through enhancing the expression and activation of indoleamine 2,3-dioxygenase in mouse lewis lung cancer cells. Int Immunopharmacol. 2014;23(1):192–204.CrossRef
18.
go back to reference Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668–81.CrossRef Liu Y, Cao X. Characteristics and significance of the pre-metastatic niche. Cancer Cell. 2016;30(5):668–81.CrossRef
19.
go back to reference Que Z, Luo B, Zhou Z, Dong C, Jiang Y, Wang L, Shi Q, Tian J. Establishment and characterization of a patient-derived circulating lung tumor cell line in vitro and in vivo; 2019.CrossRef Que Z, Luo B, Zhou Z, Dong C, Jiang Y, Wang L, Shi Q, Tian J. Establishment and characterization of a patient-derived circulating lung tumor cell line in vitro and in vivo; 2019.CrossRef
20.
go back to reference Cassileth BR, Rizvi N, Deng G, Yeung KS, Vickers A, Guillen S, Woo D, Coleton M, Kris MG. Safety and pharmacokinetic trial of docetaxel plus an Astragalus -based herbal formula for non-small cell lung cancer patients. Cancer Chemother Pharmacol. 2009;65(1):67–71.CrossRef Cassileth BR, Rizvi N, Deng G, Yeung KS, Vickers A, Guillen S, Woo D, Coleton M, Kris MG. Safety and pharmacokinetic trial of docetaxel plus an Astragalus -based herbal formula for non-small cell lung cancer patients. Cancer Chemother Pharmacol. 2009;65(1):67–71.CrossRef
21.
go back to reference Lu J, Chen J, Xu N, Wu J, Kang Y, Shen T, Kong H, Ma C, Cheng M, Shao Z. Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016;258:227.CrossRef Lu J, Chen J, Xu N, Wu J, Kang Y, Shen T, Kong H, Ma C, Cheng M, Shao Z. Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016;258:227.CrossRef
22.
go back to reference Lu J, Zhang X, Shen T, Ma C, Wu J, Kong H, Tian J, Shao Z, Zhao X, Xu L. Epigenetic profiling of H3K4Me3 reveals herbal medicine Jinfukang-Induced epigenetic alteration is involved in anti-lung cancer activity. Evid Based Complement Alternat Med. 2016;2016(4):7276161.PubMedPubMedCentral Lu J, Zhang X, Shen T, Ma C, Wu J, Kong H, Tian J, Shao Z, Zhao X, Xu L. Epigenetic profiling of H3K4Me3 reveals herbal medicine Jinfukang-Induced epigenetic alteration is involved in anti-lung cancer activity. Evid Based Complement Alternat Med. 2016;2016(4):7276161.PubMedPubMedCentral
23.
go back to reference He HL, Dan W, Jie T, Zhou XM, Li JX, Ling X. Jin Fu Kang oral liquid inhibits lymphatic endothelial cells formation and migration. Evid Based Complement Alternat Med. 2016;2016(3):1–10. He HL, Dan W, Jie T, Zhou XM, Li JX, Ling X. Jin Fu Kang oral liquid inhibits lymphatic endothelial cells formation and migration. Evid Based Complement Alternat Med. 2016;2016(3):1–10.
24.
go back to reference Zhou XM, Wang D, He HL, Tang J, Wu J, Xu L, Li JX. Bone marrow derived mesenchymal stem cells involve in the lymphangiogenesis of lung cancer and Jinfukang inhibits the involvement in vivo. J Cancer. 2017;8(10):1786–94.CrossRef Zhou XM, Wang D, He HL, Tang J, Wu J, Xu L, Li JX. Bone marrow derived mesenchymal stem cells involve in the lymphangiogenesis of lung cancer and Jinfukang inhibits the involvement in vivo. J Cancer. 2017;8(10):1786–94.CrossRef
25.
go back to reference Sun Q, Qing W, Qi R, Zou M, Gong L, Liu Y, Li DW. Inhibition of Sumoylation alleviates oxidative stress-induced retinal pigment epithelial cell senescence and represses proinflammatory gene expression. Curr Mol Med. 2018;18(9):575–83.CrossRef Sun Q, Qing W, Qi R, Zou M, Gong L, Liu Y, Li DW. Inhibition of Sumoylation alleviates oxidative stress-induced retinal pigment epithelial cell senescence and represses proinflammatory gene expression. Curr Mol Med. 2018;18(9):575–83.CrossRef
26.
go back to reference Tse AK, Chen YJ, Fu XQ, Su T, Li T, Guo H, Zhu PL, Kwan HY, Cheng BC, Cao HH, et al. Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKbeta inhibition. Redox Biol. 2017;11:562–76.CrossRef Tse AK, Chen YJ, Fu XQ, Su T, Li T, Guo H, Zhu PL, Kwan HY, Cheng BC, Cao HH, et al. Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKbeta inhibition. Redox Biol. 2017;11:562–76.CrossRef
27.
go back to reference Mcnally JP, Millen SH, Chaturvedi V, Lakes N, Terrell CE, Elfers EE, Carroll KR, Hogan SP, Andreassen PR, Kanter J. Manipulating DNA damage-response signaling for the treatment of immune-mediated diseases. Proc Natl Acad Sci U S A. 2017;114(24):201703683.CrossRef Mcnally JP, Millen SH, Chaturvedi V, Lakes N, Terrell CE, Elfers EE, Carroll KR, Hogan SP, Andreassen PR, Kanter J. Manipulating DNA damage-response signaling for the treatment of immune-mediated diseases. Proc Natl Acad Sci U S A. 2017;114(24):201703683.CrossRef
Metadata
Title
Jingfukang induces anti-cancer activity through oxidative stress-mediated DNA damage in circulating human lung cancer cells
Authors
Zujun Que
Zhiyi Zhou
Bin Luo
Changsheng Dong
Yi Jiang
Hegen Li
Jianhui Tian
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2019
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-019-2601-x

Other articles of this Issue 1/2019

BMC Complementary Medicine and Therapies 1/2019 Go to the issue