Kaempferol suppresses human gastric cancer SNU-216 cell proliferation, promotes cell autophagy, but has no influence on cell apoptosis

Abstract

Gastric cancer remains a serious threat to human health worldwide. Kaempferol is a plant-derived flavonoid compound with a wide range of pharmacological activities. This study aimed to investigate the effects of kaempferol on gastric cancer SNU-216 cell proliferation, apoptosis, and autophagy, as well as underlying potential mechanisms. Viability, proliferation, and apoptosis of SNU-216 cells after kaempferol treatment were evaluated using cell counting kit-8 assay, 5-btomo-2′-deoxyuridine incorporation assay, and annexin V-FITC/PI staining, respectively. Quantitative reverse transcription PCR was performed to measure the mRNA expressions of cyclin D1 and microRNA-181a (miR-181a) in SNU-216 cells. Cell transfection was used to down-regulate the expression of miR-181a. The protein expression levels of cyclin D1, bcl-2, bax, caspase 3, caspase 9, autophagy-related gene 7, microtubule-associated protein 1 light chain 3-I (LC3-I), LC3-II, Beclin 1, p62, mitogen-activated protein kinase (MAPK), extracellular regulated protein kinases (ERK), and phosphatidylinositol 3 kinase (PI3K) in SNU-216 cells were detected using western blotting. Results showed that kaempferol significantly suppressed SNU-216 cell viability and proliferation but had no influence on cell apoptosis. Further results suggested that kaempferol significantly induced SNU-216 cell autophagy. The expression of miR-181a in SNU-216 cells after kaempferol treatment was enhanced. Kaempferol significantly inactivated MAPK/ERK and PI3K pathways in SNU-216 cells. Suppression of miR-181a significantly reversed the kaempferol-induced MAPK/ERK and PI3K pathways inactivation in SNU-216 cells. This research demonstrated that kaempferol suppressed proliferation and promoted autophagy of human gastric cancer SNU-216 cells by up-regulating miR-181a and inactivating MAPK/ERK and PI3K pathways.

Luteolin Suppresses the Proliferation of Gastric Cancer Cells and Acts in Synergy with Oxaliplatin

“…The use of natural compounds found in food and plants for treating gastric cancer has been increasing in the past 20 years [9]. In recent years, a few studies identified therapeutic candidates, namely, quercetin [10], liquiritin [11], and kaempferol [12], for the treatment of gastric cancer via inhibition of cell proliferation and induction of apoptosis. Luteolin (LUT, Figure 1(b)) is a flavonoid which is abundantly found in vegetables and fruits such as celery, broccoli, carrots, and peppers [13].…”

Mapping Pharmacological Network of Multi-Targeting Litchi Ingredients in Cancer Therapeutics

“…bladder, breast, cervical, lung, colon, gastric, and liver cancer (Choi and Ahn, 2008;Li et al, 2009;Mylonis et al, 2010;Wang et al, 2013;Cho and Park, 2013;Huang et al, 2013;Lee et al, 2014a;Dang et al, 2015;Kim et al, 2016;Qiu et al, 2017;Drouet et al, 2018;Han et al, 2018a;Wu et al, 2018;Zhu et al, 2018;Zhang and Ma, 2019) attenuating angiogenesis AKT1, ESRRA, HIF1A, VEGFA ovarian cancer (Luo et al, 2009) inhibiting metastasis AKT1, CDH1/2, CJUN, MAPK2/3, MIR21, MMP2/9, MTOR, MYC, PIK3CA, PTEN, PTK2, RAC1, RHOA, SMAD3, SNAIL1, VIM breast, oral cancer, lung, liver, and renal carcinoma (Lin et al, 2013;Jo et al, 2015) (Lee et al, 2017a;Hung et al, 2017;Zhu et al, 2018) promoting apoptosis and autophagy AKT1, ATG7, ATM, BAD, BAX, BCL2/ L1, BECN1, BID, BIK, CASP3/7/8/9, CFLIP, CYC, DDIT3, EHMT2, EREG, ERN1, FAS, H2AX, JNK, LC3I/II/III, MAP2K1/2, MAPK1/3, MTCO2, TERT, TNFRSF10A…”

“…bladder, breast, cervical, colon, colorectal, endometrial, gastric, lung, and ovarian cancer (Nguyen et al, 2003;Li et al, 2009;Luo et al, 2011;Xie et al, 2013;Lee et al, 2014b;Kim et al, 2016;Yi et al, 2016;Kashafi et al, 2017;Zhao et al, 2017;Choi et al, 2018;Chuwa et al, 2018;Kim et al, 2018;Zhu et al, 2018;Zhang and Ma, 2019) sensitizing chemotherapy ABCC6, AKT1, BAX, BCL2/L1, BIRC5, CASP3/7/8/9/10, CDKN1A, FAS, JAK1, JNK, MAPK1/14, MYC, NFKB, PARP1, PIK3CA, ROS1, STAT3, TNFRSF10A, XIAP, ovarian, lung, and colorectal cancer (Luo et al, 2010;Kuo et al, 2015;Riahi-Chebbi et al, 2019) inhibiting metabolism SLC2A1/16A1 breast cancer (Azevedo et al, 2015) enhancing immunity CSF2, MAP2K1, MAPK2/3, PKC, PLC prostate cancer (Bandyopadhyay et al, 2008) Luteolin attenuating angiogenesis NOTCH1, VEGFA gastric cancer (Zang et al, 2017a) inhibiting metastasis AKT1, CDH1/2, CTNNB1, CYCD1, HES1, HEY1, MIR384, MMP2/3/7/9/16, NFKB, NFKBIA, NOTCH1, PIK3CA, PTN, SNAIL1/2, STAT3, VIM gastric, pancreatic, breast, lung, and colorectal cancer (Chen et al, 2013;Huang et al, 2015b;Zang et al, 2017b;Yao et al, 2019) promoting apoptosis AIF, AKT1, ANO1, AURKB, BANF1, BAX, BCL2/L1, BIRC5, CASP3/9, CCND1/E, CDKN1A, DEDD2, ENG, GAK, HSP90, HTERT, MAPK1/14/3, MCL1, MCL4, MIR107/139/155/21/ 224/301/340/34A/422A/5703/630, MTOR, MYC, NFE2L2, NFKBIA, NOTCH1, PIK3CA, PTPN6, SIRT1, STAT3, TET1, TP53, VRK1, breast, colon, gastric, lung, pancreatic, and prostate cancer (Kim et al, 2012b;Ma et al, 2015;Han et al, 2016;Song et al, 2017;Seo et al, 2017;Li et al, 2018;Jiang et al, 2018;Kang et al, 2019) sens...…”

Polyphenol-Mediated Autophagy in Cancer: Evidence of In Vitro and In Vivo Studies

“…Other studies evaluated the effect of the flavonol kaempferol, found in several plant derivatives (e.g., apples, onion, leeks, citrus, grapes, gingko biloba, St. John's wort, red wine), on several types of cancer [82][83][84][85][86]. The antitumor effects of kaempferol were evaluated in hepatocellular carcinoma (HCC) cells.…”