Pectolinarigenin inhibits cell viability, migration and invasion and induces apoptosis via a ROS‑mitochondrial apoptotic pathway in melanoma cells

Deng,Yuanle; Zhang,Qianyu; Li,Yali; Wang,Liqun; Yang,Shuping; Chen,Xiaotong; Gan,Cailin; He,Fang; Ye,Tinghong; Yin,Wenya

doi:10.3892/ol.2020.11977

Pectolinarigenin inhibits cell viability, migration and invasion and induces apoptosis via a ROS‑mitochondrial apoptotic pathway in melanoma cells

Authors:
- Yuanle Deng
- Qianyu Zhang
- Yali Li
- Liqun Wang
- Shuping Yang
- Xiaotong Chen
- Cailin Gan
- Fang He
- Tinghong Ye
- Wenya Yin
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Affiliations: Department of Nutrition, Food Safety and Toxicology, West China School of Public Health and Healthy Food Evaluation Research Center, Sichuan University, Chengdu, Sichuan 610064, P.R China, State Key of Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610064, P.R China
Published online on: August 12, 2020 https://doi.org/10.3892/ol.2020.11977
Article Number: 116
Copyright: © Deng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pectolinarigenin a plant secondary metabolite that has various biological effects, including the inhibition of melanogenesis and tumor growth. Melanoma has a high degree of malignancy, with rapid metastasis and severe drug resistance, explaining the need for new candidate drugs that inhibit tumor growth and metastasis. However, the pharmacological action and mechanism of pectolinarigenin on the growth and metastasis of melanoma remain elusive. Thus, the present study aimed to investigate the role of pectolinarigenin in melanoma cell proliferation, apoptosis, migration and invasion. Apoptotic and metastasis‑associated proteins were analyzed using western blotting. The results demonstrated that pectolinarigenin treatment resulted in growth inhibition and apoptosis induction in melanoma cells, arising from the loss of mitochondrial transmembrane potential, reactive oxygen species and the altered expression of apoptosis‑associated proteins. In addition, wound‑healing and Transwell assays demonstrated the potential of pectolinarigenin to impair the migration and invasion of melanoma cells in accordance with the changes in the expression of the associated proteins. Therefore, the results of the present study suggested that pectolinarigenin may serve a pivotal role in promoting melanoma cell apoptosis and reducing metastasis, and may thus be a promising potential candidate for an anti‑melanoma treatment strategy.

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1	Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
3	Zheng Y, Wang K, Wu Y, Chen Y, Chen X, Hu CW and Hu F: Pinocembrin induces ER stress mediated apoptosis and suppresses autophagy in melanoma cells. Cancer Lett. 431:31–42. 2018. View Article : Google Scholar : PubMed/NCBI
4	Xiong J, Wang Y, Gu Y, Xue Y, Dang L and Li Y: CDK5RAP1 targeting NF-κB signaling pathway in human malignant melanoma A375 cell apoptosis. Oncol Lett. 15:4767–4774. 2018.PubMed/NCBI
5	Slominski A, Zmijewski MA and Pawelek J: L-tyrosine and L-dihydroxyphenylalanine as hormone-like regulators of melanocyte functions. Pigment Cell Melanoma Res. 25:14–27. 2012. View Article : Google Scholar : PubMed/NCBI
6	Slominski A, Tobin DJ, Shibahara S and Wortsman J: Melanin pigmentation in mammalian skin and its hormonal regulation. Physiol Rev. 84:1155–1228. 2004. View Article : Google Scholar : PubMed/NCBI
7	Prota G: Melanins, melanogenesis and melanocytes: Looking at their functional significance from the chemist's viewpoint. Pigment Cell Res. 13:283–293. 2000. View Article : Google Scholar : PubMed/NCBI
8	Meredith P and Sarna T: The physical and chemical properties of eumelanin. Pigment Cell Res. 19:572–594. 2006. View Article : Google Scholar : PubMed/NCBI
9	Sarna T: Properties and function of the ocular melanin-a photobiophysical view. J Photochem Photobiol B. 12:215–258. 1992. View Article : Google Scholar : PubMed/NCBI
10	Lee S, Lee DH, Kim JC, Um BH, Sung SH, Jeong LS, Kim YK, Kim SN, et al: Pectolinarigenin, an aglycone of pectolinarin, has more potent inhibitory activities on melanogenesis than pectolinarin. Biochem Biophys Res Commun. 493:765–772. 2017. View Article : Google Scholar : PubMed/NCBI
11	Slominski A, Kim TK, Brożyna AA, Janjetovic Z, Brooks DLP, Schwab LP, Skobowiat C, Jóźwicki W and Seagroves TN: The role of melanogenesis in regulation of melanoma behavior: Melanogenesis leads to stimulation of HIF-1α expression and HIF-dependent attendant pathways. Arch Biochem Biophys. 563:79–93. 2014. View Article : Google Scholar : PubMed/NCBI
12	Slominski A, Zbytek B and Slominski R: Inhibitors of melanogenesis increase toxicity of cyclophosphamide and lymphocytes against melanoma cells. Int J Cancer. 124:1470–1477. 2009. View Article : Google Scholar : PubMed/NCBI
13	Brożyna AA, Jozwicki W, Roszkowski K, Filipiak J and Slominski AT: Melanin content in melanoma metastases affects the outcome of radiotherapy. Oncotarget. 7:17844–17853. 2016. View Article : Google Scholar : PubMed/NCBI
14	Zhang K, Lei J, He Y, Yang X, Zhang Z, Hao D, Wang B and He B: A flavonoids compound inhibits osteoclast differentiation by attenuating RANKL induced NFATc-1/c-Fos induction. Int Immunopharmacol. 61:150–155. 2018. View Article : Google Scholar : PubMed/NCBI
15	Bonesi M, Tundis R, Deguin B, Loizzo MR and Menichini F, Tillequin F and Menichini F: In vitro biological evaluation of novel 7-O-dialkylaminoalkyl cytotoxic pectolinarigenin derivatives against a panel of human cancer cell lines. Bioorg Med Chem Lett. 18:5431–5434. 2008. View Article : Google Scholar : PubMed/NCBI
16	Deng Y, Li Y, Yang F, Zeng A, Yang S, Luo Y, Zhang Y, Xie Y, Ye T, Xia Y and Yin W: The extract from Punica granatum (pomegranate) peel induces apoptosis and impairs metastasis in prostate cancer cells. Biomed Pharmacother. 93:976–984. 2017. View Article : Google Scholar : PubMed/NCBI
17	Li Y, Yang F, Zheng W, Hu M, Wang J, Ma S, Deng Y, Luo Y, Ye T and Yin W: Punica granatum (pomegranate) leaves extract induces apoptosis through mitochondrial intrinsic pathway and inhibits migration and invasion in non-small cell lung cancer in vitro. Biomed Pharmacother. 80:227–235. 2016. View Article : Google Scholar : PubMed/NCBI
18	Tuong W, Cheng LS and Armstrong AW: Melanoma: Epidemiology, diagnosis, treatment, and outcomes. Dermatol Clin. 30:113–124. 2012. View Article : Google Scholar : PubMed/NCBI
19	Panth N, Manandhar B and Paudel KR: Anticancer activity of Punica granatum (pomegranate): A review. Phytother Res. 31:568–578. 2017. View Article : Google Scholar : PubMed/NCBI
20	Wang CZ, Calway TD, Wen XD, Smith J, Yu C, Wang Y, Mehendale SR and Yuan CS: Hydrophobic flavonoids from Scutellaria baicalensis induce colorectal cancer cell apoptosis through a mitochondrial-mediated pathway. Int J Oncol. 42:1018–1026. 2013. View Article : Google Scholar : PubMed/NCBI
21	Elkady AI, Abu-Zinadah OA and Hussein RA: Crude flavonoid extract of the medicinal herb nigella sativa inhibits proliferation and induces apoptosis in breast cancer cells. J Biomater Tiss Eng. 7:1235–1249. 2017. View Article : Google Scholar
22	Xu F, Gao X and Pan H: Pectolinarigenin inhibits non-small cell lung cancer progression by regulating the PTEN/PI3K/AKT signaling pathway. Oncol Rep. 40:3458–3468. 2018.PubMed/NCBI
23	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar : PubMed/NCBI
24	Rahman N, Dhadi SR, Deshpande A and Ramakrishna W: Rice callus suspension culture inhibits growth of cell lines of multiple cancer types and induces apoptosis in lung cancer cell line. BMC Complement Altern Med. 16:4272016. View Article : Google Scholar : PubMed/NCBI
25	Hunter AM, LaCasse EC and Korneluk RG: The inhibitors of apoptosis (IAPs) as cancer targets. Apoptosis. 12:1543–1568. 2007. View Article : Google Scholar : PubMed/NCBI
26	Autret A and Martin SJ: Emerging role for members of the Bcl-2 family in mitochondrial morphogenesis. Mol Cell. 36:355–363. 2009. View Article : Google Scholar : PubMed/NCBI
27	Namura S, Zhu JM, Fink K, Endres M, Srinivasan A, Tomaselli KJ, Yuan J and Moskowitz MA: Activation and cleavage of caspase-3 in apoptosis induced by experimental cerebral ischemia. J Neurosci. 18:3659–3668. 1998. View Article : Google Scholar : PubMed/NCBI
28	Lu M, Kong Q, Xu X, Lu H, Lu Z, Yu W, Zuo B, Su J and Guo R: Pectolinarigenin-a flavonoid compound from cirsium japonicum with potential anti-proliferation activity in MCF-7 breast cancer cell. Tropical J Pharma Res. 13:2252014. View Article : Google Scholar
29	Guo L, Yin Z, Wen L, Xin J, Gao X and Zheng X: Flower extracts from Paeonia decomposita and Paeonia ostii inhibit melanin synthesis via cAMP-CREB-associated melanogenesis signaling pathways in murine B16 melanoma cells. J Food Biochem. 43:e127772019. View Article : Google Scholar : PubMed/NCBI
30	Liu-Smith F and Meyskens FL: Molecular mechanisms of flavonoids in melanin synthesis and the potential for the prevention and treatment of melanoma. Mol Nutr Food Res. 60:1264–1274. 2016. View Article : Google Scholar : PubMed/NCBI
31	Alfadda AA and Sallam RM: Reactive oxygen species in health and disease. J Biomed Biotechnol. 2012:9364862012. View Article : Google Scholar : PubMed/NCBI
32	Wang J and Yi J: Cancer cell killing via ROS: To increase or decrease, that is the question. Cancer Biol Ther. 7:1875–1884. 2008. View Article : Google Scholar : PubMed/NCBI
33	Yang SP, Zhang YG, Luo Y, Xu B, Yao Y, Deng Y, Yang F, Ye T, Wang G, Cheng Z, et al: Hinokiflavone induces apoptosis in melanoma cells through the ROS-mitochondrial apoptotic pathway and impairs cell migration and invasion. Biomed Pharmacother. 103:101–110. 2018. View Article : Google Scholar : PubMed/NCBI
34	Talmadge JE and Fidler IJ: AACR centennial series: The biology of cancer metastasis: Historical perspective. Cancer Res. 70:5649–5669. 2010. View Article : Google Scholar : PubMed/NCBI
35	Fidler IJ: The pathogenesis of cancer metastasis: The ‘seed and soil’ hypothesis revisited. Nat Rev Cancer. 3:453–458. 2003. View Article : Google Scholar : PubMed/NCBI
36	Kamran MZ and Gude RP: Preclinical evaluation of the antimetastatic efficacy of pentoxifylline on A375 human melanoma cell line. Biomed Pharmacother. 66:617–626. 2012. View Article : Google Scholar : PubMed/NCBI
37	Fietz S, Einspanier R, Hoppner S, Hertsch B and Bondzio A: Determination of MMP-2 and −9 activities in synovial fluid of horses with osteoarthritic and arthritic joint diseases using gelatin zymography and immunocapture activity assays. Equine Vet J. 40:266–271. 2008. View Article : Google Scholar : PubMed/NCBI
38	Si L, Yan X, Hao W, Ma X, Ren H, Ren B, Li D, Dong Z and Zheng Q: Licochalcone D induces apoptosis and inhibits migration and invasion in human melanoma A375 cells. Oncol Rep. 39:2160–2170. 2018.PubMed/NCBI
39	Li Y, Gan C, Zhang Y, Yu Y, Fan C, Deng Y, Zhang Q, Yu X, Zhang Y, Wang L, et al: Inhibition of Stat3 signaling pathway by natural product pectolinarigenin attenuates breast cancer metastasis. Front Pharmacol. 10:11952019. View Article : Google Scholar : PubMed/NCBI
40	Zhang T, Li S, Li J, Yin F, Hua Y, Wang Z, Lin B, Wang H, Zou D, Zhou Z, et al: Natural product pectolinarigenin inhibits osteosarcoma growth and metastasis via SHP-1-mediated STAT3 signaling inhibition. Cell Death Dis. 7:e24212016. View Article : Google Scholar : PubMed/NCBI
41	Gan C, Li Y, Yu Y, Yu X, Liu H, Zhang Q, Yin W, Yu L and Ye T: Natural product pectolinarigenin exhibits potent anti-metastatic activity in colorectal carcinoma cells in vitro and in vivo. Bioorg Med Chem. 27:1150892019. View Article : Google Scholar : PubMed/NCBI