Shikonin promotes autophagy in BXPC‑3 human pancreatic cancer cells through the PI3K/Akt signaling pathway

Shi,Shuqing; Cao,Haimei

doi:10.3892/ol.2014.2293

Shikonin promotes autophagy in BXPC‑3 human pancreatic cancer cells through the PI3K/Akt signaling pathway

Authors:
- Shuqing Shi
- Haimei Cao
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Affiliations: Department of General Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan 410013, P.R. China
Published online on: June 26, 2014 https://doi.org/10.3892/ol.2014.2293
Pages: 1087-1089

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Abstract

The present study aimed to investigate the effect of shikonin on autophagy in BXPC‑3 human pancreatic cancer cells and its underlying mechanism. Cell viability was assessed using the Cell Counting Kit‑8 assay and the expression of light chain (LC) 3, p62, phosphoinositide 3‑kinase (PI3K), Akt, phosphorylated (p)‑PI3K and p‑Akt was analyzed using western blot analysis. Following treatment with 1 µmol/l shikonin for 48 h and 2.5 and 5 µmol/l shikonin for 24 and 48 h, the viability of the BXPC‑3 cells was found to be significantly reduced and the protein expression of LC3‑II/LC3‑I was observed to be increased, while the protein expression of p62, PI3K, Akt, p‑PI3K and p‑Akt was decreased. These findings suggest that shikonin promotes autophagy in BXPC‑3 cells and that the underlying mechanism may be associated with the PI3K/Akt signaling pathway.

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1	Li D, Xie K, Wolff R and Abbruzzese JL: Pancreatic cancer. Lancet. 363:1049–1057. 2004.
2	Lorin S, Hamaï A, Mehrpour M and Codogno P: Autophagy regulation and its role in cancer. Semin Cancer Biol. 23:361–379. 2013.
3	Mizushima N, Levine B, Cuervo AM and Klionsky DJ: Autophagy fights disease through cellular self-digestion. Nature. 451:1069–1075. 2008.
4	Levine B and Yuan J: Autophagy in cell death: an innocent convict? J Clin Invest. 115:2679–2688. 2005.
5	Klionsky DJ, Abeliovich H, Agostinis P, et al: Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy. 4:151–175. 2008.
6	Hsieh MJ, Tsai TL, Hsieh YS, et al: Dioscin-induced autophagy mitigates cell apoptosis through modulation of PI3K/Akt and ERK and JNK signaling pathways in human lung cancer cell lines. Arch Toxicol. 87:1927–1937. 2013.
7	Prasad R, Vaid M and Katiyar SK: Grape proanthocyanidin inhibit pancreatic cancer cell growth in vitro and in vivo through induction of apoptosis and by targeting the PI3K/Akt pathway. PLoS One. 7:e430642012.
8	Wang CY, Bai XY and Wang CH: Traditional chinese medicine: a treasured natural resource of anticancer drug research and development. Am J Chin Med. 42:543–559. 2014.
9	Liu Z, Chen S, Cai J, et al: Traditional Chinese medicine syndrome-related herbal prescriptions in treatment of malignant tumors. J Tradit Chin Med. 33:19–26. 2913.
10	Gong K and Li W: Shikonin, a Chinese plant-derived naphthoquinone, induces apoptosis in hepatocellular carcinoma cells through reactive oxygen species: A potential new treatment for hepatocellular carcinoma. Free Radic Biol Med. 51:2259–2271. 2011.
11	Yao Y and Zhou Q: A novel antiestrogen agent Shikonin inhibits estrogen-dependent gene transcription in human breast cancer cells. Breast Cancer Res Treat. 121:233–240. 2010.
12	Wiench B, Eichhorn T, Paulsen M and Efferth T: Shikonin directly targets mitochondria and causes mitochondrial dysfunction in cancer cells. Evid Based Complement Alternat Med. 2012:7260252012.
13	Sabater L, Calvete J, Aparisi L, et al: Pancreatic and periampullary tumors: morbidity, mortality, functional results and long-term survival. Cir Esp. 86:159–166. 2009.(In Spanish).
14	Yue Z, Jin S, Yang C, et al: Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor. Proc Natl Acad Sci USA. 100:15077–15082. 2003.
15	Yang ZJ, Chee CE, Huang S and Sinicrope F: Autophagy modulation for cancer therapy. Cancer Biol Ther. 11:169–176. 2011.
16	Bjørkøy G, Lamark T, Brech A, et al: p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol. 171:603–614. 2005.
17	Martelli AM, Evangelisti C, Follo MY, et al: Targeting the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin signaling network in cancer stem cells. Curr Med Chem. 18:2715–2726. 2011.
18	Singh BN, Kumar D, Shankar S and Srivastava RK: Rottlerin induces autophagy which leads to apoptotic cell death through inhibition of PI3K/Akt/mTOR pathway in human pancreatic cancer stem cells. Biochem Pharmacol. 84:1154–1163. 2012.
19	Wu H, Xie J, Pan Q, et al: Anticancer agent shikonin is an incompetent inducer of cancer drug resistance. PLoS One. 8:e527062013.
20	Yang H, Zhou P, Huang H, et al: Shikonin exerts antitumor activity via proteasome inhibition and cell death induction in vitro and in vivo. Int J Cancer. 124:2450–2459. 2009.