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Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer

  • Authors:
    • Guang Yang
    • Jun Xing
    • Batuer Aikemu
    • Jing Sun
    • Minhua Zheng
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200001, P.R. China, Department of PET/CT Center, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi 030001, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 32
    |
    Published online on: February 18, 2021
       https://doi.org/10.3892/or.2021.7983
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Abstract

Kaempferol (KF), a flavonoid compound isolated from herbal medicines, has been reported to play a significant role in inhibiting certain types of cancer. Although recent studies reported that KF exerted inhibitive activity on liver cancer, they failed to elucidate the signaling pathways and synergistic effects in combination with chemotherapeutic drugs currently in use in the clinical setting. In the present study, the signaling pathways and synergistic effects of KF in liver cancer cells were investigated. Nine liver cancer cell lines were used to assess the inhibitive activity and synergistic effects of KF. Cellular behavioral experiments, such as viability, colony formation, cell cycle arrest, apoptotic, wound healing, and Transwell assays were used to assess the effects of KF on the proliferation, apoptosis, migration, and invasion of liver cancer cells. Western blotting was performed to validate the key signaling pathway elements underlying those cellular behaviors. KF exhibited inhibitory effects on nine liver cancer cell lines in time‑ and dose‑dependent manners and was mostly nontoxic to the normal hepatocyte cells. The combination of KF and doxorubicin revealed a stronger inhibitive effect on the viability of liver cancer cells. Combination therapy also revealed higher suppressive effects on colony formation, cell cycle progression, survival, DNA damage response, and mitochondrial function. By western blotting assay, mitochondrial and caspase signaling pathways were determined to be involved in proliferation inhibition. In wound healing and Transwell invasion assays, combination therapy also exhibited more robust inhibitory activity in blocking the migration and invasion of liver cancer cells. PI3K/mTOR/MMP protein pathways were also revealed to be related to cell migration inhibition. KF alone exhibited an inhibitory effect on proliferation, migration, and invasion of liver cancer cells, and its synergistic effects revealed stronger inhibitory activities. The present data indicated that KF is a promising candidate as a complementary medicine to conventional chemotherapeutic drugs.
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1 

Forner A, Reig M and Bruix J: Hepatocellular carcinoma. Lancet. 391:1301–1314. 2012. View Article : Google Scholar

2 

Anwanwan D, Singh SK, Singh S, Saikam V and Singh R: Challenges in liver cancer and possible treatment approaches. Biochim Biophys Acta Rev Cancer. 1873:1883142020. View Article : Google Scholar : PubMed/NCBI

3 

Jiao B and Gao JJ: Intensive research on the prospective use of complementary and alternative medicine to treat systemic lupus erythematosus. Drug Discov Ther. 7:167–171. 2013.PubMed/NCBI

4 

Huang H, Peng X and Zhong C: Idiopathic pulmonary fibrosis: The current status of its epidemiology, diagnosis, and treatment in China. Intractable Rare Dis Res. 2:88–93. 2013.PubMed/NCBI

5 

Gao J, Inagaki Y, Li X, Kokudo N and Tang W: Research progress on natural products from traditional Chinese medicine in treatment of Alzheimer's disease. Drug Discov Ther. 7:46–57. 2013.PubMed/NCBI

6 

Melendez-Martinez AJ, Nascimento AF, Wang Y, Liu C, Mao Y and Wang XD: Effect of tomato extract supplementation against high-fat diet-induced hepatic lesions. Hepatobiliary Surg Nutr. 2:198–208. 2013.PubMed/NCBI

7 

Tao Z, Gao J, Zhang G, Xue M, Yang W, Tong C and Yuan Y: Shufeng Jiedu Capsule protect against acute lung injury by suppressing the MAPK/NF-κB pathway. BioSci Trends. 8:45–51. 2014. View Article : Google Scholar : PubMed/NCBI

8 

Qi FH, Wang ZX, Cai PP, Zhao L, Gao JJ, Okudo N, Li AY, Han JQ and Tang W: Traditional Chinese medicine and related active compounds: A review of their role on hepatitis B virus infection. Drug Discov Ther. 7:212–24. 2013. View Article : Google Scholar : PubMed/NCBI

9 

Xia J, Inagaki Y, Gao J, Qi F, Song P, Han G, Sawakami T, Gao B, Luo C, Kokudo N, et al: Combination of Cinobufacini and Doxorubicin increases apoptosis of hepatocellular carcinoma cells through the Fas- and mitochondria-mediated pathways. Am J Chin Med. 45:1537–1556. 2017. View Article : Google Scholar : PubMed/NCBI

10 

Xia J, Rong L, Sawakami T, Inagaki Y, Song P, Hasegawa K, Sakamoto Y and Tang W: Shufeng Jiedu Capsule and its active ingredients induce apoptosis, inhibit migration and invasion, and enhances doxorubicin therapeutic efficacy in hepatocellular carcinoma. Biomed Pharmacother. 99:921–930. 2018. View Article : Google Scholar : PubMed/NCBI

11 

Wong R, Sagar CM and Sagar SM: Integration of Chinese medicine into supportive cancer care: A modern role for an ancient tradition. Cancer Treat Rev. 27:235–246. 2001. View Article : Google Scholar : PubMed/NCBI

12 

Holland TM, Agarwal P, Wang Y, Leurgans SE, Bennett DA, Booth SL and Morris MC: Dietary flavonols and risk of Alzheimer dementia. Neurology. 29:e1749–e1756. 2020. View Article : Google Scholar

13 

Veeresham C, Rama Rao A and Asres K: Aldose reductase inhibitors of plant origin. Phytotherapy Research. 28:317–333. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Khalil MI and Sulaiman SA: The potential role of honey and its polyphenols in preventing heart diseases: A review. Afr J Tradit Complement Altern Med. 7:315–321. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Chen AY and Chen YC: A review of the dietary flavonoid, kaempferol on human health and cancer chemoprevention. Food Chem. 138:2099–2107. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Niestroy J, Barbara A, Herbst K, Rode S, van Liempt M and Roos PH: Single and concerted effects of benzo[a]pyrene and flavonoids on the AhR and Nrf2-pathway in the human colon carcinoma cell line Caco-2. Toxicol In Vitro. 25:671–683. 2011. View Article : Google Scholar : PubMed/NCBI

17 

Calderón-Montaño JM, Burgos-Morón E, Pérez-Guerrero C and López-Lázaro M: A review on the dietary flavonoid kaempferol. Mini Rev Med Chem. 11:298–344. 2011. View Article : Google Scholar : PubMed/NCBI

18 

Kim SH and Choi KC: Anti-cancer effect and underlying mechanism(s) of kaempferol, a phytoestrogen, on the regulation of apoptosis in diverse cancer cell models. Toxicol Res. 29:229–234. 2013. View Article : Google Scholar : PubMed/NCBI

19 

Speth PA, van Hoesel QG and Haanen C: Clinical pharmacokinetics of doxorubicin. Clin Pharmacokinet. 15:15–31. 1988. View Article : Google Scholar : PubMed/NCBI

20 

Chatterjee K, Zhang J, Honbo N and Karliner JS: Doxorubicin cardiomyopathy. Cardiology. 115:155–162. 2010. View Article : Google Scholar : PubMed/NCBI

21 

Kaczmarek A, Brinkman BM, Heyndrickx L, Vandenabeele P and Krysko DV: Severity of doxorubicin-induced small intestinal mucositis is regulated by the TLR-2 and TLR-9 pathways. J Pathol. 226:598–608. 2012. View Article : Google Scholar : PubMed/NCBI

22 

Bun S, Yunokawa M, Tamaki Y, Shimomura A, Shimoi T, Kodaira M, Shimizu C, Yonemori K, Fujiwara Y, Makino Y, et al: Symptom management: The utility of regional cooling for hand-foot syndrome induced by pegylated liposomal doxorubicin in ovarian cancer. Support Care Cancer. 26:2161–2166. 2018. View Article : Google Scholar : PubMed/NCBI

23 

Lin J, Fang L, Li H, Li Z, Lyu L, Wang H and Xiao J: Astragaloside IV alleviates doxorubicin induced cardiomyopathy by inhibiting NADPH oxidase derived oxidative stress. Eur J Pharmacol. 859:1724902019. View Article : Google Scholar : PubMed/NCBI

24 

Li J, Wu Y, Wang D, Zou L, Fu C, Zhang J and Leung GP: Oridonin synergistically enhances the anti-tumor efficacy of doxorubicin against aggressive breast cancer via pro-apoptotic and anti-angiogenic effects. Pharmacol Res. 146:1043132019. View Article : Google Scholar : PubMed/NCBI

25 

Xu Z, Chen L, Xiao Z, Zhu Y, Jiang H, Jin Y, Gu C, Wu Y, Wang L, Zhang W, et al: Potentiation of the anticancer effect of doxorubicinin drug-resistant gastric cancer cells by tanshinone IIA. Phytomedicine. 51:58–67. 2018. View Article : Google Scholar : PubMed/NCBI

26 

Caldwell S and Park SH: The epidemiology of hepatocellular cancer: From the perspectives of public health problem to tumor biology. Journal of Gastroenterology. 44 (Suppl 19):S96–S101. 2009. View Article : Google Scholar

27 

El-Serag HB, Marrero JA, Rudolph L and Reddy KR: Diagnosis and treatment of hepatocellular carcinoma. Gastroenterology. 134:1752–1763. 2008. View Article : Google Scholar : PubMed/NCBI

28 

Gnoni A, Santini D, Scartozzi M, Russo A, Licchetta A, Palmieri V, Lupo L, Faloppi L, Palasciano G, Memeo V, et al: Hepatocellular carcinoma treatment over sorafenib: Epigenetics, microRNAs and microenvironment. Is there a light at the end of the tunnel? Expert Opin Ther Targets. 19:1623–1635. 2015. View Article : Google Scholar

29 

Han G, Xia J, Gao J, Inagaki Y, Tang W and Kokudo N: Anti-tumor effects and cellular mechanisms of resveratrol. Drug Discov Ther. 9:1–12. 2015. View Article : Google Scholar : PubMed/NCBI

30 

Anand David AV, Arulmoli R and Parasuraman S: Overviews of biological importance of quercetin: A bioactive flavonoid. Pharmacogn Rev. 10:84–89. 2016. View Article : Google Scholar : PubMed/NCBI

31 

Ren J, Lu Y, Qian Y, Chen B, Wu T and Ji G: Recent progress regarding kaempferol for the treatment of various diseases. Exp Ther Med. 18:2759–2776. 2019.PubMed/NCBI

32 

Seydi E, Salimi A, Rasekh HR, Mohsenifar Z and Pourahmad J: Selective cytotoxicity of luteolin and kaempferol on cancerous hepatocytes obtained from Rat model of hepatocellular carcinoma: Involvement of ROS-mediated mitochondrial targeting. Nutr Cancer. 70:594–604. 2018. View Article : Google Scholar : PubMed/NCBI

33 

Han B, Yu YQ, Yang QL, Shen CY and Wang XJ: Kaempferol induces autophagic cell death of hepatocellular carcinoma cells via activating AMPK signaling. Oncotarget. 8:86227–86239. 2017. View Article : Google Scholar : PubMed/NCBI

34 

Guo H, Ren F, Zhang L, Zhang X, Yang R, Xie B, Li Z, Hu Z, Duan Z and Zhang J: Kaempferol induces apoptosis in HepG2 cells via activation of the endoplasmic reticulum stress pathway. Mol Med Rep. 13:2791–2800. 2016. View Article : Google Scholar : PubMed/NCBI

35 

Huang WW, Chiu YJ, Fan MJ, Lu HF, Yeh HF, Li KH, Chen PY, Chung JG and Yang JS: Kaempferol induced apoptosis via endoplasmic reticulum stress and mitochondria-dependent pathway in human osteosarcoma U-2 OS cells. Mol Nutr Food Res. 54:1585–1595. 2010. View Article : Google Scholar : PubMed/NCBI

36 

Zhu G, Liu X, Li H, Yan Y, Hong X and Lin Z: Kaempferol inhibits proliferation, migration, and invasion of liver cancer HepG2 cells by down-regulation of microRNA-21. Int J Immunopathol Pharmacol. 32:20587384188143412018. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Yang G, Xing J, Aikemu B, Sun J and Zheng M: Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer. Oncol Rep 45: 32, 2021.
APA
Yang, G., Xing, J., Aikemu, B., Sun, J., & Zheng, M. (2021). Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer. Oncology Reports, 45, 32. https://doi.org/10.3892/or.2021.7983
MLA
Yang, G., Xing, J., Aikemu, B., Sun, J., Zheng, M."Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer". Oncology Reports 45.4 (2021): 32.
Chicago
Yang, G., Xing, J., Aikemu, B., Sun, J., Zheng, M."Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer". Oncology Reports 45, no. 4 (2021): 32. https://doi.org/10.3892/or.2021.7983
Copy and paste a formatted citation
x
Spandidos Publications style
Yang G, Xing J, Aikemu B, Sun J and Zheng M: Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer. Oncol Rep 45: 32, 2021.
APA
Yang, G., Xing, J., Aikemu, B., Sun, J., & Zheng, M. (2021). Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer. Oncology Reports, 45, 32. https://doi.org/10.3892/or.2021.7983
MLA
Yang, G., Xing, J., Aikemu, B., Sun, J., Zheng, M."Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer". Oncology Reports 45.4 (2021): 32.
Chicago
Yang, G., Xing, J., Aikemu, B., Sun, J., Zheng, M."Kaempferol exhibits a synergistic effect with doxorubicin to inhibit proliferation, migration, and invasion of liver cancer". Oncology Reports 45, no. 4 (2021): 32. https://doi.org/10.3892/or.2021.7983
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