Hematoporphyrin monomethyl ether‑mediated sonodynamic therapy induces A‑253 cell apoptosis

Zhang,Yi; Bi,Liangjia; Hu,Zheng; Cao,Wenwu; Zhuang,Deshu

doi:10.3892/ol.2020.11419

Hematoporphyrin monomethyl ether‑mediated sonodynamic therapy induces A‑253 cell apoptosis

Authors:
- Yi Zhang
- Liangjia Bi
- Zheng Hu
- Wenwu Cao
- Deshu Zhuang
View Affiliations

Affiliations: Department of Stomatology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China, Condensed Matter Science and Technology Institute, Harbin Institute of Technology, Harbin, Heilongjiang 150080, P.R. China
Published online on: February 21, 2020 https://doi.org/10.3892/ol.2020.11419
Pages: 3223-3228
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

It has been found that >90% of oral cancer patients suffer from squamous cell carcinoma (SCC). The 5‑year survival rate of SCC is ~50%, despite the availability of different treatments. Sonodynamic therapy (SDT) has been developed as a novel therapy for cancer, resisting bacterial infection and inhibiting atherosclerotic plaque progression. The present study investigated the efficacy of hematoporphyrin monomethyl ether (HMME)‑mediated SDT on the A‑253 epidermoid cancer cell line. The cytotoxicity of HMME and the survival rate of cells following SDT were examined by the MTT assay. Apoptosis and necrosis of cells were detected using flow cytometry with Annexin V and propidium iodide (PI) staining, and fluorescence microscopy with Hoechst 33258 and PI staining. Intracellular reactive oxygen species (ROS) and Ca2+ levels were measured using a fluorescence microscope based on 2',7'‑dichlorofluorescein diacetate and ﬂuo‑3/acetoxymethylester, respectively. Results of the MTT assay demonstrated that a lower concentration (<10 µg/ml) of HMME had no significant effect on the A‑253 cells, but SDT combined with ultrasonic treatment for 1 min and 10 µg/ml HMME decreased the cell survival rate by 27%. Flow cytometry analysis revealed that A‑253 cells in the SDT group had a higher rate of late apoptosis compared with the control group. Furthermore, fluorescence quantitation of apoptotic A‑253 cells demonstrated that the percentages of apoptotic cells were increased in the ultrasound and SDT group compared with those in the control group. In the present study, the ROS level in the SDT group was elevated compared with that in the control group. The Ca2+ levels were increased to 181.2 and 268.7% in the ultrasound and SDT groups, respectively, relative to the control group. Taken together, the findings of the present study demonstrated that HMME‑SDT significantly induces the apoptosis of A‑253 cells together with intracellular ROS generation and Ca2+ overload. Thus, HMME‑SDT may be a promising treatment option for patients with SCC.

View Figures

View References

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	Pérez-Sayáns M, Suárez-Peñaranda JM, Gayoso-Diz P, Barros-Angueira F, Gándara-Rey JM and García-García A: The role of p21Waf1/CIP1 as a Cip/Kip type cell-cycle regulator in oral squamous cell carcinoma (Review). Med Oral Patol Oral Cir Bucal. 18:e219–e225. 2013. View Article : Google Scholar : PubMed/NCBI
3	Somasundaram RT, Kaur J, Leong I, MacMillan C, Witterick IJ, Walfish PG and Ralhan R: Subcellular differential expression of Ep-ICD in oral dysplasia and cancer is associated with disease progression and prognosis. BMC Cancer. 16:4862016. View Article : Google Scholar : PubMed/NCBI
4	Taghavi N and Yazdi I: Prognostic factors of survival rate in oral squamous cell carcinoma: Clinical, histologic, genetic and molecular concepts. Arch Iran Med. 18:314–319. 2015.PubMed/NCBI
5	Kerker FA, Adler W, Brunner K, Moest T, Wurm MC, Nkenke E, Neukam FW and von Wilmowsky C: Anatomical locations in the oral cavity where surgical resections of oral squamous cell carcinomas are associated with a close or positive margin-a retrospective study. Clin Oral Investig. 22:1625–1630. 2018. View Article : Google Scholar : PubMed/NCBI
6	Su X, Wang P, Wang X, Cao B, Li L and Liu Q: Apoptosis of U937 cells induced by hematoporphyrin monomethyl ether-mediated sonodynamic action. Cancer Biother Radiopharm. 28:207–217. 2013. View Article : Google Scholar : PubMed/NCBI
7	Zhuang D, Hou C, Bi L, Han J, Hao Y, Cao W and Zhou Q: Sonodynamic effects of hematoporphyrin monomethyl ether on staphylococcus aureus in vitro. FEMS Microbiol Lett. 361:174–180. 2014. View Article : Google Scholar : PubMed/NCBI
8	Yang Y, Liu Y, Chen X, Gong J, Huang Z, Wang W, Shi Y, Wang Y, Yao J, Shen Z, et al: 5-aminolevulinic acid-mediated sonodynamic therapy alleviates atherosclerosis via enhancing efferocytosis and facilitating a shift in the Th1/Th2 balance toward Th2 polarization. Cell Physiol Biochem. 47:83–96. 2018. View Article : Google Scholar : PubMed/NCBI
9	Bilmin K, Kujawska T, Secomski W, Nowicki A and Grieb P: 5-Aminolevulinic acid-mediated sonosensitization of rat RG2 glioma cells in vitro. Folia Neuropathol. 54:234–240. 2016. View Article : Google Scholar : PubMed/NCBI
10	Hao D, Song Y, Che Z and Liu Q: Calcium overload and in vitro apoptosis of the C6 glioma cells mediated by sonodynamic therapy (hematoporphyrin monomethyl ether and ultrasound). Cell Biochem Biophys. 70:1445–1452. 2014. View Article : Google Scholar : PubMed/NCBI
11	Su X, Wang P, Yang S, Zhang K, Liu Q and Wang X: Sonodynamic therapy induces the interplay between apoptosis and autophagy in K562 cells through ROS. Int J Biochem Cell Biol. 60:82–92. 2015. View Article : Google Scholar : PubMed/NCBI
12	Li Y, Zhou Q, Deng Z, Pan M, Liu X, Wu J, Yan F and Zheng H: IR-780 Dye as a sonosensitizer for sonodynamic therapy of breast tumor. Sci Rep. 6:259682016. View Article : Google Scholar : PubMed/NCBI
13	Bullon P, Cordero MD, Quiles JL, Morillo JM, del Carmen Ramirez-Tortosa M and Battino M: Mitochondrial dysfunction promoted by Porphyromonas gingivalis lipopolysaccharide as a possible link between cardiovascular disease and periodontitis. Free Radic Biol Med. 50:1336–1343. 2011. View Article : Google Scholar : PubMed/NCBI
14	Wang X, Jia Y, Wang P, Liu Q and Zheng H: Current status and future perspectives of sonodynamic therapy in glioma treatment. Ultrason Sonochem. 37:592–599. 2017. View Article : Google Scholar : PubMed/NCBI
15	Sun X, Xu H, Shen J, Guo S, Shi S, Dan J, Tian F and Tian Y and Tian Y: Real-time detection of intracellular reactive oxygen species and mitochondrial membrane potential in THP-1 macrophages during ultrasonic irradiation for optimal sonodynamic therapy. Ultrason Sonochem. 22:7–14. 2015. View Article : Google Scholar : PubMed/NCBI
16	Li Y, Wang P, Zhao P, Zhu S, Wang X and Liu Q: Apoptosis induced by sonodynamic treatment by protoporphyrin IX on MDA-MB-231 cells. Ultrasonics. 52:490–496. 2012. View Article : Google Scholar : PubMed/NCBI
17	Liu ZR, Chen SQ, Zou YW, Wu XY, Li HY, Wang XQ, Shi Y and Niu HX: Hypochlorite modified albumins promote cell death in the tubule interstitium in rats via mitochondrial damage in obstructive nephropathy and the protective effects of antioxidant peptides. Free Radic Res. 52:616–628. 2018. View Article : Google Scholar : PubMed/NCBI
18	Li N, Sun M, Wang Y, Lv Y, Hu Z, Cao W, Zheng J and Jiao X: Effect of cell cycle phase on the sensitivity of SAS cells to sonodynamic therapy using low-intensity ultrasound combined with 5-aminolevulinic acid in vitro. Mol Med Rep. 12:3177–3183. 2015. View Article : Google Scholar : PubMed/NCBI
19	Lv Y, Zheng J, Zhou Q, Jia L, Wang C, Liu N, Zhao H, Ji H, Li B and Cao W: Antiproliferative and apoptosis-inducing effect of exo-protoporphyrin IX based sonodynamic therapy on human oral squamous cell carcinoma. Sci Rep. 7:409672017. View Article : Google Scholar : PubMed/NCBI
20	Sisto M, Lisi S, D'Amore M, Mitolo V and Scagliusi P: Anti-Ro and anti-La autoantibodies induce TNF-alpha production by human salivary gland cells: An in vitro study. Reumatismo. 59:221–226. 2007.PubMed/NCBI
21	Li W, Fei JF, Yang Q, Li BL, Lin C, Yue Q and Meng QG: Acute toxic effects of sonodynamic therapy on hypertrophic scar fibroblasts of rabbit ears. Genet Mol Res. 14:4203–4214. 2015. View Article : Google Scholar : PubMed/NCBI
22	Xie R, Xu T, Zhu J, Wei X, Zhu W, Li L, Wang Y, Han Y, Zhou J and Bai Y: The combination of glycolytic inhibitor 2-deoxyglucose and microbubbles increases the effect of 5-aminolevulinic acid-sonodynamic therapy in liver cancer cells. Ultrasound Med Biol. 43:2640–2650. 2017. View Article : Google Scholar : PubMed/NCBI
23	Xiong W, Wang P, Hu J, Jia Y, Wu L, Chen X, Liu Q and Wang X: A new sensitizer DVDMS combined with multiple focused ultrasound treatments: An effective antitumor strategy. Sci Rep. 5:174852015. View Article : Google Scholar : PubMed/NCBI
24	Sun H, Ge W, Gao X, Wang S, Jiang S, Hu Y, Yu M and Hu S: Apoptosis-promoting effects of hematoporphyrin monomethyl ether-sonodynamic therapy (HMME-SDT) on endometrial cancer. PLoS One. 10:e01379802015. View Article : Google Scholar : PubMed/NCBI
25	Wang F, Gao Q, Guo S, Cheng J, Sun X, Li Q, Wang T, Zhang Z, Cao W and Tian Y: The sonodynamic effect of curcumin on THP-1 cell-derived macrophages. BioMed Res Int. 2013:7372642013.PubMed/NCBI
26	Qin P, Han T, Yu ACH and Xu L: Mechanistic understanding the bioeffects of ultrasound-driven microbubbles to enhance macromolecule delivery. J Control Release. 272:169–181. 2018. View Article : Google Scholar : PubMed/NCBI
27	Li J, Yue W, Huang Z, Chen ZQ, Zhan Q, Ren FB, Liu JY and Fu SB: Calcium overload induces C6 rat glioma cell apoptosis in sonodynamic therapy. Int J Radiat Biol. 87:1061–1066. 2011. View Article : Google Scholar : PubMed/NCBI
28	Tian J, Gan Y, Pan C, Zhang M, Wang X, Tang X and Peng X: Nerol-induced apoptosis associated with the generation of ROS and Ca²⁺ overload in saprotrophic fungus Aspergillus flavus. Appl Microbiol Biotechnol. 102:6659–6672. 2018. View Article : Google Scholar : PubMed/NCBI
29	Tran TA, Roger S, Le Guennec JY, Tranquart F and Bouakaz A: Effect of ultrasound-activated microbubbles on the cell electrophysiological properties. Ultrasound Med Biol. 33:158–163. 2007. View Article : Google Scholar : PubMed/NCBI
30	Lentacker I, De Cock I, Deckers R, De Smedt SC and Moonen CT: Understanding ultrasound induced sonoporation: Definitions and underlying mechanisms. Adv Drug Deliv Rev. 72:49–64. 2014. View Article : Google Scholar : PubMed/NCBI