Apigenin induces apoptosis by regulating Akt and MAPK pathways in human melanoma cell A375SM

Woo,Joong‑Seok; Choo,Gang‑Sik; Yoo,Eun‑Seon; Kim,Sung‑Hyun; Lee,Jae‑Han; Han,So‑Hee; Kim,Hyeong‑Jin; Jung,Soo‑Hyun; Park,Young‑Seok; Kim,Byeong‑Soo; Kim,Sang‑Ki; Park,Byung‑Kwon; Cho,Sung‑Dae; Nam,Jeong‑Seok; Choi,Chang‑Sun; Che,Jeong‑Hwan; Jung,Ji‑Youn

doi:10.3892/mmr.2020.11572

Apigenin induces apoptosis by regulating Akt and MAPK pathways in human melanoma cell A375SM

Authors:
- Joong‑Seok Woo
- Gang‑Sik Choo
- Eun‑Seon Yoo
- Sung‑Hyun Kim
- Jae‑Han Lee
- So‑Hee Han
- Hyeong‑Jin Kim
- Soo‑Hyun Jung
- Young‑Seok Park
- Byeong‑Soo Kim
- Sang‑Ki Kim
- Byung‑Kwon Park
- Sung‑Dae Cho
- Jeong‑Seok Nam
- Chang‑Sun Choi
- Jeong‑Hwan Che
- Ji‑Youn Jung
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Affiliations: Department of Companion and Laboratory Animal Science, Kongju National University, Yesan, Chungcheongnam 32439, Republic of Korea, Department of Oral Pathology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul 03080, Republic of Korea, Gwangju Institute of Science and Technology, School of Life Sciences, Gwangju 61005, Republic of Korea, Biomedical Center for Animal Resource Development, Seoul National University College of Medicine, Seoul 03080, Republic of Korea, Biomedical Research Institute, Seoul National University Hospital, Seoul 03080, Republic of Korea
Published online on: October 8, 2020 https://doi.org/10.3892/mmr.2020.11572
Pages: 4877-4889
Copyright: © Woo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Apigenin, an aromatic compound, exhibits antioxidant, anti‑inflammatory and anti‑viral effects. The present study aimed to investigate the effects of apigenin on cell proliferation and apoptosis of human melanoma cells A375P and A375SM. Therefore, melanoma cells were treated with apigenin to determine its anti‑proliferative and survival effects, using wound healing and MTT assays. The results revealed that melanoma cell viability was decreased in a dose‑dependent manner. Furthermore, chromatin condensation, indicating apoptosis, was significantly increased in a dose‑dependent manner, as demonstrated by DAPI staining. In addition, increased apoptosis rate following treatment with apigenin was confirmed by Annexin V‑propidium iodide staining. The changes in the expression levels of apoptosis‑related proteins in A375P and A375SM melanoma cells were subsequently detected using western blot analysis. The results demonstrated that the protein expression levels of Bcl‑2 were decreased, whereas those of Bax, cleaved poly ADP‑ribose polymerase, cleaved caspase‑9 and p53 were upregulated in a dose‑dependent manner in apigenin‑treated cells compared with those noted in untreated cells. In addition, in apigenin‑treated A375P cells, phosphorylated (p)‑p38 was upregulated and p‑extracellular signal‑regulated kinase (ERK), p‑c‑Jun N‑terminal kinase (JNK) and p‑protein kinase B (Akt) were downregulated. However, in A375SM cells, apigenin treatment increased p‑ERK and p‑JNK and decreased p‑p38 and p‑Akt protein expression levels. Subsequently, the inhibitory effect of apigenin on tumor growth was investigated in vivo. Tumor volume was significantly reduced in the 25 and 50 mg/kg apigenin‑treated groups compared with the control group. Additionally, a TUNEL assay was performed to detect apoptotic cells. Immunohistochemical staining also revealed elevated p‑ERK expression in the apigenin‑treated group compared with the control group. Overall, the findings of the present study indicated that apigenin attenuated the growth of A375SM melanoma cells by inducing apoptosis via regulating the Akt and mitogen‑activated protein kinase signaling pathways.

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