Anticancer Effects of Piperine‑Free Piper nigrum Extract on Cholangiocarcinoma Cell Lines
Aman Tedasen2,3, Araya Khoka4, Siribhorn Madla2, Somchai Sriwiriyajan4, Potchanapond Graidist2,3★★ Corresponding author
- 1Department of Biomedical Sciences, Faculty of Medicine, Prince of Songkla University, Thailand.
- 2The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Thailand.
- 3Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla, Thailand.
CORRESPONDENCE
Potchanapond Graidist
The Excellent Research Laboratory of Cancer Molecular Biology, Prince of Songkla University, Thailand.
Received: 01-08-2019; Revised: 30-09-2019.
Volume 16, Issue 68S · pp. S28–S38 · PUBLISHED 31 March 2020 · DOI: 10.4103/pm.pm_288_19
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ABSTRACT
Objective: In this present study, we explored the anticancer effects of PFPE on cholangiocarcinoma (CCA). Materials and Methods: 3‑(4,5‑dimethyl thiazol‑2‑yl)‑2,5‑diphenyltetrazolium bromide assay was performed to analyze cytotoxic potential of PFPE whereas deoxyribonucleic acid (DNA) fragmentation followed by Western blot analysis were used. Results: PFPE composed of alkaloid, flavonoid, amide, lignans, opioid, and steroid. This crude extract represented cytotoxic effect against CCA cells which stronger than dichloromethane P. nigrum crude extract and piperine, especially on KKU‑M213 (median inhibition concentration [IC50] at 13.70 µg/ml) and TFK‑1 (IC50 at 15.30 µg/ml). Interestingly, PFPE showed lower cytotoxicity against normal human cholangiocyte MMNK‑1 cells (IC50 at 19.65 µg/ ml) than KKU‑M213 and TFK‑1 cells. Then, the molecular mechanisms of PFPE were firstly evaluated by DNA fragmentation followed by Western blot analysis. The degradation of DNA was observed on KKU‑M213 and TFK‑1 cells after treatment with PFPE at day 2. Then, proliferation proteins including topoisomerase II, AKT8 virus oncogene cellular homolog, avian myelocytomatosis virus oncogene cellular homolog, cyclin D1, signal transducer and activator of transcription 3, cyclooxygenase‑2, and nuclear factor kappa‑light‑chain‑enhancer of activated B cells (NF‑kB) were decreased and p21 was increased. Furthermore, apoptotic proteins, such as tumor protein p53, Bcl-2‑associated X protein, and p53 upregulated modulator of apoptosis were upregulated. Meanwhile, antiapoptotic protein B‑cell lymphoma 2 was down‑regulated. Conclusion: These results indicated that PFPE inhibited CCA through the down‑regulation of cell proliferation and induction of apoptosis pathway.
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Tedasen, A., Khoka, A., Madla, S., Sriwiriyajan, S., & Graidist, P. (2020). Anticancer Effects of Piperine‑Free Piper nigrum Extract on Cholangiocarcinoma Cell Lines. Pharmacognosy Magazine, 16(68S), S28–S38. https://doi.org/10.4103/pm.pm_288_19