Pien Tze Huang induces apoptosis and inhibits proliferation of 5-fluorouracil-resistant colorectal carcinoma cells via increasing miR-22 expression

Abstract

The well-known traditional Chinese medicine formula Pien Tze Huang (PZH) has long been used to treat various malignancies, including colorectal cancer (CRC). It was recently reported that PZH possesses the ability to overcome multidrug resistance in CRC cells. In the present study, a 5-fluorouracil (5-FU) resistant human CRC cell line (HCT-8/5-FU) was used to further evaluate the effect of PZH on chemotherapy (chemo)-resistance and investigate the mechanisms through which this occurs. The results identified that PZH significantly reduced the viability and cell density of HCT-8/5-FU cells in a dose- and time-dependent manner (P<0.05). PZH inhibited cell survival, reduced the proportion of cells in S-phase, and suppressed the expression of pro-proliferative proteins cyclin D1 and cyclin-dependent kinase 4. In addition, PZH treatment induced nuclear condensation and fragmentation, activated caspase-9 and −3 and increased the pro-apoptotic Bcl-2-associated X protein/B-cell lymphoma 2 protein ratio. Furthermore, PZH treatment upregulated the expression of microRNA-22 (miR-22) and downregulated the expression of c-Myc (a target gene of miR-22). In conclusion, the findings from the present study suggest that PZH can overcome chemo-resistance in cancer cells, likely through increasing miR-22 expression, and by reversing the imbalance between levels of proliferation and apoptosis.

Pien Tze Huang ameliorates DSS‑induced colonic inflammation in a mouse colitis model through inhibition of the IL‑6/STAT3 pathway

“…Natural products, including TCM, have received great interest since they have long been used to clinically treat inflammatory diseases and are relatively toxicity-free (9)(10)(11)(12). PZH is a well-known TCM formula which has been used in China and Southeast Asia for centuries to clinically treat a variety of inflammatory diseases (33)(34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50). However, the precise mechanism of anti-inflammatory activity of PZH remains largely unknown.…”

Therapeutic Potential of Pien-Tze-Huang: A Review on Its Chemical Composition, Pharmacology, and Clinical Application

“…The in vivo anti-cancer potential of PTH has been recognized in different xenograft animal models [31]. PTH not only overcomes multidrug resistance (MDR) in HCT-8/5-fluorouracil (5-FU) cells but also attenuates 5-FU-induced intestinal mucositis in CT-26 tumor-bearing xenograft mice [34,35,36]. Furthermore, it exhibits synergistic effects when combined with chemotherapy drugs, such as fluorouracil, oxaliplatin, and capecitabine, in clinical in China [37,38].…”

“…Several studies demonstrated that PTH may be a potential multidrug resistance (MDR)-reversing drug that restores the sensitivity of MDR cancer cells [34,35,36]. PTH dose-dependently inhibits the proliferation of HCT-8/5-FU cells, increases the intercellular accumulation of Rhodamine-123, and downregulates ATP-binding cassette subfamily C member 2 (ABCC2) expressions in HCT-8/5-FU cells, indicating its ability to overcome MDR.…”

Uncovering the Mechanism of the Effects of Pien-Tze-Huang on Liver Cancer Using Network Pharmacology and Molecular Docking

“…In China, PTH is clinically used to protect the liver [ 11 , 12 ], treat hepatitis [ 13 ], improve liver fibrosis [ 14 ], and treat liver cancer [ 15 – 17 ]. Studies on the effects of PTH on lung cancer [ 18 ], intestinal cancer [ 19 , 20 ], osteosarcoma [ 21 ], and liver cancer [ 22 ] have been reported, but the active ingredients of PTH on liver cancer and the relevant molecular mechanisms are still unclear.…”