Anti‑tumor effects of bakuchiol on human gastric carcinoma cell lines are mediated through PI3K/AKT and MAPK signaling pathways

Lv,Long; Liu,Bo

doi:10.3892/mmr.2017.7696

Anti‑tumor effects of bakuchiol on human gastric carcinoma cell lines are mediated through PI3K/AKT and MAPK signaling pathways

Authors:
- Long Lv
- Bo Liu
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Affiliations: Department of Normal Surgical,, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, Hubei 441053, P.R. China, Department of Oncology, Xiangyang Central Hospital, Hubei University of Arts and Science, Xiangyang, Hubei 441053, P.R. China
Published online on: October 3, 2017 https://doi.org/10.3892/mmr.2017.7696
Pages: 8977-8982

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Abstract

Bakuchiol is extracted from Psoralea corylifolia, a member of the Leguminosae family, has been used in Indian Ayurvedic and Chinese traditional medicine, and it possesses an anticancer effect. The primary aim of the present study was to identify the molecular mechanisms underlying the anticancer effect of bakuchiol monoterpenes. Bakuchiol treatment significantly inhibited NUGC3 human gastric cancer cell viability in a concentration dependent manner. In addition, bakuchiol significantly increased the apoptotic cell population in the sub‑G1 phase, and Annexin‑V‑fluorescein isothiocyanate/propidium iodide double staining confirmed the increase in apoptosis. Nuclear fragmentation and the formation of apoptotic organelles were promoted in bakuchiol‑treated NUGC3 cells. Western blotting results indicated that bakuchiol treatment significantly decreased procaspase‑3,6,8,9 and poly (ADP‑ribose) polymerase (PARP) expression levels, increased cleaved caspase‑3 and cleaved PARP expression levels, and increased the B cell lymphoma‑2 associated X, apoptosis regulator:B cell lymphoma‑extra large ratio. Bakuchiol‑treated NUGC3 cells demonstrated significantly reduced phosphorylated (p‑) protein kinase B (AKT) protein expression levels and elevated p‑extracellular signal related kinase 1/2 (ERK1/2), p‑c‑Jun N‑terminal kinase (JNK) and p‑p38. Bakuchiol‑induced cell death was mitochondrial dependent, through modulation of phosphoinositide 3‑kinase/AKT and mitogen‑activated protein kinase signaling pathways. These findings demonstrated that bakuchiol possesses potential for treating human gastric cancer.

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1	Guggenheim DE and Shah MA: Gastric cancer epidemiology and risk factors. J Surg Oncol. 107:230–236. 2013. View Article : Google Scholar : PubMed/NCBI
2	Herszényi L and Tulassay Z: Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci. 14:249–258. 2010.PubMed/NCBI
3	Ren J, Huang HJ, Gong Y, Yue S, Tang LM and Cheng SY: MicroRNA-206 suppresses gastric cancer cell growth and metastasis. Cell Biosci. 4:262014. View Article : Google Scholar : PubMed/NCBI
4	Jaing JB, Thesson DP, Dusak BA, Dexter DL, Kang GJ and Hamel E: Synthesis and biological evaluation of 2-styrylquinazolin-4(3H)-ones, a new class of antimitotic anticancer agents which inhibit tubulin polymerization. J Med Chem. 33:1721–1728. 1990. View Article : Google Scholar : PubMed/NCBI
5	Zouhiri F, Danet M, Bénard C, Normad-Boyle M, Mouscadet JF, Leh H, Thomas CM, Mbemba G, d'Angelo J and Desmaële D: HIV-1 replication inhibitors of the styrylquinoline class: Introduction of an additional carboxyl group at the C-5 position of the quinolone. Tetrahedron Lett. 46:2201–2205. 2005. View Article : Google Scholar
6	Eltahla AA, Lim KL, Eden JS, Kelly AG, Mackenzie JM and White PA: Nonnucleoside inhibitors of norovirus RNA Polymerase: Scaffolds for rational drug design. Antimicrob Agents Chemother. 58:3115–3123. 2014. View Article : Google Scholar : PubMed/NCBI
7	Lee IK, Han MS, Lee MS, Kim YS and Yun BS: Styrylpyrones from the medicinal fungus Phellinus baumii and their antioxidant properties. Bioorg Med Chem Lett. 20:5459–5461. 2010. View Article : Google Scholar : PubMed/NCBI
8	Bapat SA, Mali AM, Koppikar CB and Kurrey NK: Stem and progenitor like cells contribute to the aggressive behaviour of human epithelial ovarian cancer. Cancer Res. 65:3025–3029. 2005. View Article : Google Scholar : PubMed/NCBI
9	Bradford MM: A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 72:248–254. 1976. View Article : Google Scholar : PubMed/NCBI
10	Vansteenkiste J: Improving patient management in metastatic non-small cell lung cancer. Lung Cancer. 57 Suppl 2:S12–S17. 2007. View Article : Google Scholar : PubMed/NCBI
11	Chevalier A and Kindersley D: The encyclopedia of medicinal plants. ISBN 9-780751-303148. London: 1996
12	Duke JA and Ayensu ES: Medicinal plants of China Inc. ISBN 0-917256,. 20:41985.
13	Sun NJ, Woo SH, Cassady JM and Snapka RM: DNA polymerase and topoisomerase II inhibitors from Psoralea corylifolia. J Nat Prod. 61:362–366. 1998. View Article : Google Scholar : PubMed/NCBI
14	Katsura H, Tsukiyama RI, Suzuki A and Kobayashi M: In vitro antimicrobial activities of bakuchiol against oral microorganisms. Antimicrob Agents Chemother. 45:3009–3013. 2001. View Article : Google Scholar : PubMed/NCBI
15	Reddy MV, Thota N, Sangwan PL, Malhotra P, Ali F, Khan IA, Chimni SS and Koul S: Novel bisstyryl derivatives of bakuchiol: Targeting oral cavity pathogens. Eur J Med Chem. 45:3125–3134. 2010. View Article : Google Scholar : PubMed/NCBI
16	Shi Y: Caspase activation: Revisiting the induced proximity model. Cell. 117:855–858. 2004. View Article : Google Scholar : PubMed/NCBI
17	Park SJ, Ahmad F, Philp A, Baar K, Williams T, Luo H, Ke H, Rehmann H, Taussig R, Brown AL, et al: Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases. Cell. 148:421–433. 2012. View Article : Google Scholar : PubMed/NCBI
18	Lee DH, Park KI, Park HS, Kang SR, Nagappan A, Kim JA, Kim EH, Lee WS, Hah YS, Chung HJ, et al: Flavonoids isolated from Korea Citrus aurantium L. Induce G2/M phase arrest and apoptosis in human gastric cancer AGS cells. Evid Based Complement Alternat Med. 2012:5159012012.PubMed/NCBI
19	Hussain AR, Al-Rasheed M, Manogaran PS, Al-Hussein KA, Platanias LC, Al Kuraya K and Uddin S: Curcumin induces apoptosis via inhibition of PI3′-kinase/AKT pathway in acute T cell leukemias. Apoptosis. 11:245–254. 2006. View Article : Google Scholar : PubMed/NCBI
20	Gururajan M, Dasu T, Shahidain S, Jennings CD, Robertson DA, Rangnekar VM and Bondada S: Spleen tyrosine kinase (Syk), a novel target of curcumin, is required for B lymphoma growth. J Immunol. 178:111–121. 2007. View Article : Google Scholar : PubMed/NCBI
21	Raman M, Chen W and Cobb MH: Differential regulation and properties of MAPKs. Oncogene. 26:3100–3112. 2007. View Article : Google Scholar : PubMed/NCBI
22	van den Brink MR, Kapeller R, Pratt JC, Chang JH and Burakoff SJ: The extracellular signal-regulated kinase pathway is required for activation-induced cell death of T cells. J Biol Chem. 274:11178–11185. 1999. View Article : Google Scholar : PubMed/NCBI
23	Basu S, Bayoumy S, Zhang Y, Lozano J and Kolesnick R: BAD enables ceramide to signal apoptosis via Ras and Raf-1. J Biol Chem. 273:30419–30426. 1998. View Article : Google Scholar : PubMed/NCBI
24	Faris M, Kokot N, Latinis K, Kasibhatla S, Green DR, Koretzky GA and Nel A: The c-Jun N-terminal kinase cascade plays a role in stress-induced apoptosis in Jurkat cells by up-regulating Fas ligand expression. J Immunol. 160:134–144. 1998.PubMed/NCBI
25	Dhanasekaran DN and Reddy EP: JNK signaling in apoptosis. Oncogene. 27:6245–6225. 2008. View Article : Google Scholar : PubMed/NCBI
26	Kang YJ, Zhou ZX, Wang GW, Buridi A and Klein JB: Suppression by metallothionein of doxorubicin-induced cardiomyocyte apoptosis through inhibition of p38 mitogen-activated protein kinases. J Biol Chem. 275:13690–13698. 2000. View Article : Google Scholar : PubMed/NCBI
27	Sinha K, Das J, Pal PB and Sil PC: Oxidative stress: The mitochondria-dependent and mitochondria-independent pathways of apoptosis. Arch Toxicol. 87:1157–1180. 2013. View Article : Google Scholar : PubMed/NCBI