Pien Tze Huang inhibits metastasis of human colorectal carcinoma cells via modulation of TGF-β1/ZEB/miR-200 signaling network

Abstract

Tumor metastasis, a complex process involving the spread of malignant tumor cells from a primary tumor site to a distant organ, is a major cause of failure of cancer chemotherapy. Epithelial-mesenchymal transition (EMT) is a critical step for the initiation of cancer metastasis. The processes of EMT and metastasis are highly regulated by a double-negative feedback loop consisting of TGF-β1/ZEB pathway and miR-200 family, which therefore has become a promising target for cancer chemotherapy. Pien Tze Huang (PZH), a well-known traditional Chinese formula first prescribed in the Ming Dynasty, has been demonstrated to be clinically effective in the treatment of various types of human malignancy including colorectal cancer (CRC). Our published data proposed that PZH was able to induce apoptosis, inhibit cell proliferation and tumor angiogenesis, leading to the suppression of CRC growth in vitro and in vivo. To further elucidate the mode of action of PZH, in the present study we evaluated its effects on the metastatic capacities of human colorectal carcinoma HCT-8 cells and investigated the underlying molecular mechanisms. We found that PZH significantly inhibited the migration and invasion of HCT-8 cells in a dose-dependent manner. In addition, PZH treatment inhibited the expression of key mediators of TGF-β1 signaling, such as TGF-β1, Smad2/3 and Smad4. Moreover, PZH treatment suppressed the expression of ZEB1 and ZEB2, two critical target genes of TGF-β1 pathway, leading to a decrease in the expression of mesenchymal marker N-cadherin and an increased expression of epithelial marker E-cadherin. Furthermore, PZH treatment upregulated the expression of miR-200a, miR-200b and miR-200c. Collectively, our findings in this study suggest that PZH can inhibit metastasis of colorectal cancer cells via modulating TGF-β1/ZEB/miR-200 signaling network, which might be one of the mechanisms whereby PZH exerts its anticancer function.

Pien Tze Huang inhibits the growth of hepatocellular carcinoma cells by upregulating miR‑16 expression

“…The TCM treatment of cancer has received widespread attention due to its therapeutic efficacy and relatively few side effects. Previous studies have demonstrated that the commonly used TCM formula PZH can inhibit the growth and metastasis of colorectal cancer cells (34)(35)(36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46). However, its effects on HCC and the underlying mechanisms remain unclear.…”

“…Pien Tze Huang (PZH), a well-known TCM formula that originated in the Chinese Ming Dynasty >450 years ago, has been widely used in China and Southeast Asia as a remedy for various diseases, including cancer (36). It was previously demonstrated that PZH may inhibit colon cancer growth via multiple mechanisms (37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49) and PZH has exhibited promising therapeutic effects in clinical trials regarding HCC (50,51). However, the effect of PZH on HCC, including on miR-16 expression level, has not been evaluated; therefore, the present study aimed to explore the effect of PZH on the proliferation and apoptosis of the HCC BEL-7402 cell line.…”

Pien Tze Huang inhibits the proliferation of colorectal cancer cells by increasing the expression of miR-34c-5p

“…PZH, as a TCM formula, has been demonstrated to have cancer activity via a number of mechanisms, including the stimulation of apoptosis, inhibition of proliferation and regulati multiple downstream cancer-related signaling molecules in CRC cells. Previous studies have identified that PZH can regulate a number of miRNAs, such as the miR-200 family (19).…”

Scutellaria?barbata D. Don inhibits migration and invasion of colorectal cancer cells via suppression of PI3K/AKT and TGF‑β/Smad signaling pathways

“…Tumor metastasis is a complex process, and is highly regulated by multiple mechanisms, including aberrant activation of the phosphoinositide 3-kinase (PI3K)/AKT and transforming growth factor (TGF)-β/Smad pathways (8)(9)(10)(11). Furthermore, a large number of studies have shown that matrix metalloproteinase (MMP) overexpression is involved in numerous malignant tumors, including esophageal cancer, breast cancer, liver cancer and rectal cancer (12)(13)(14)(15)(16).…”