In vitro evaluation of the antiproliferative activity of Piper retrofractum on human cholangiocarcinoma cells
Keywords:apoptosis, cholangiocarcinoma, mitochondrial dysfunction, Piper retrofractum, reactive oxygen species
To explore the effects of Piper retrofractum (PR) on CCA cells death, apoptosis, and migration. Two CCA cells, KKU-100 and KKU-M452, were used in this study. Cells were observed the growth by sulforhodamine B (SRB), colony formation, cell cycle arrest, and reactive oxygen species (ROS) formation. Migratory capability was determined by Wound healing and matrigel migration method. From the results indicated that PR significantly suppressed the growth of both CCA cells through reducing cancer cells number, inhibiting colony formation, and arresting cell cycle distribution at G0/G1 phase in KKU-100 cells and S to G2/M phase in KKU-M452 cells. Furthermore, PR strongly increased late apoptosis and necrosis in both cancer cells via increasing ROS formation and decreasing mitochondrial function. In line with this finding, PR extracts suppressed migration in Wound healing and matrigel migration assay, especially in KKU-100 cells. Collectively, the present study suggested PR serve as an anticancer drug for the prevention and treatment of CCA.
Barreto JN, Mc Cullough KB, Ice LL, Smith JA (2014). Antineoplastic agents and the associated myelosuppressive effects: a review. Journal of Pharmacy Practice 27(5):440-446. https://doi.org/10.1177/0897190014546108
Bhandari S, Babu U, Garg H (1988). A lignan from Piper chaba stem. Phytochemistry 47(7):1435-1436. https://doi.org/10.1016/S0031-9422(97)00681-X.
Buranrat B (2022). Anticancer potential of Piper retrofractum on breast cancer MCF-7 cells via induction of cell death and reduction of cell migration. Pharmacognosy Magazine 18:532-539. https://doi.org/10.4103/pm.pm_455_21
Gatto M, Alvaro D (2010). New insights on cholangiocarcinoma. World Journal of Gastrointestinal Oncology 2(3):136-145. https://doi.org/10.4251/wjgo.v2.i3.136
Hasan AEZ, Suryani, Mulia K, Setiyono A, Silip JJ (2016). Antiproliferation activities of Indonesian java chili, Piper retrofractum Vahl., against breast cancer cells (MCF-7). Der Pharmacia Lettre 8(18):141-147.
He H, Guo WW, Xu RR, Chen XQ, Zhang N, …, Wang XM (2016). Alkaloids from piper longum protect dopaminergic neurons against inflammation-mediated damage induced by intranigral injection of lipopolysaccharide. BMC Complementary Medicine and Therapies 16(1):412-423. https://doi.org/10.1186/s12906-016-1392-6
Jafri A, Siddiqui S, Rais J, Ahmad MS, Kumar S, Jafar T, …, Arshad M (2019). Induction of apoptosis by piperine in human cervical adenocarcinoma via ROS mediated mitochondrial pathway and caspase-3 activation. EXCLI Journal 18:154-164. https://doi.org/10.17179/excli2018-1928
Lai LH, Fu QH, Liu Y, Jiang K, Guo QM, Chen QY, …, Shen JG (2012). Piperine suppresses tumor growth and metastasis in vitro and in vivo in a 4T1 murine breast cancer model. Acta Pharmacologica Sinica 33(4):523-530. https://doi.org/10.1038/aps.2011.209
Shi GZ, Yuan Y, Jiang GJ, Ge ZJ, Zhou J, Gong DJ, …, Huang SD (2012). PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma. BMC Cancer 12:97-109. https://doi.org/10.1186/1471-2407-12-97
Squadroni M, Tondulli L, Gatta G, Mosconi S, Beretta G, Labianca R (2017). Cholangiocarcinoma. Critical Reviews in Oncology/Hematology 116:11-31. https://doi.org/10.1016/j.critrevonc.2016.11.012
Sripa B, Bethony J, Sithithaworn P, Kaewkes S, Mairiang E, Loukas A, …, Brindley P (2011). Opisthorchiasis and Opisthorchis-associated cholangiocarcinoma in Thailand and Laos. Acta Tropica 120:158-168. https://doi.org/10.1016/j.actatropica.2010.07.006
Sriwiriyajan S, Ninpesh T, Sukpondma Y, Nasomyon T, Graidist P (2014). Cytotoxicity screening of plants of genus piper in breast cancer cell lines. Tropical Journal of Pharmaceutical Research 13:921-928. https://doi.org/10.4314/tjpr.v13i6.14
Toth M, Sohail A, Fridman R (2012). Assessment of gelatinases (MMP-2 and MMP-9) by gelatin zymography. Methods in Molecular Biology 878:121-135. https://doi.org/10.1385/1-59259-136-1:163
van der Gaag N, Kloek J, de Bakker J, Musters B, Geskus R, Busch O, …, van Gulik T (2012). Survival analysis and prognostic nomogram for patients undergoing resection of extrahepatic cholangiocarcinoma. Annals of Oncology 23(10):2642-2649. https://doi.org/10.1093/annonc/mds077
Wu HJ, Chu PY (2019). Role of cancer stem cells in cholangiocarcinoma and therapeutic implications. International Journal of Molecular Sciences 20(17):1-28. https://doi.org/10.3390/ijms20174154
Yoo ES, Choo GS, Kim SH, Woo JS, Kim HJ, Park YS, …, Jung JY (2019). Antitumor and apoptosis-inducing effects of piperine on human melanoma cells. Anticancer Research 39(4):1883-1892. https://doi.org/10.21873/anticanres.13296
How to Cite
Copyright (c) 2023 Benjaporn BURANRAT
This work is licensed under a Creative Commons Attribution 4.0 International License.
Open Access Journal:
The journal allows the author(s) to retain publishing rights without restriction. Users are allowed to read, download, copy, distribute, print, search, or link to the full texts of the articles, or use them for any other lawful purpose, without asking prior permission from the publisher or the author.