Triptolide and management of systemic malignancies besides pancreatic carcinomas

Abstract

The recent article by Zhou et al was highly interesting and thought provoking. The authors have clearly shown that triptolide administration is associated with up-regulation of the Bax gene, resulting in an attenuating effect on cell growth in gastrointestinal malignancies such as pancreatic carcinomas. The article by Zhou et al is all the more important because it highlights the rapidly increasing role of triplodide in the management of systemic malignancies. For instance, triptolide acts on the PI3K/Akt/NF-κB pathway, thereby enhancing apoptosis secondary to the administration of bortezomib in multiple myeloma cells. Similar synergisms are seen when triptolide is administered along with 5-fluoruracil for the management of colonic carcinomas. Similarly, triptolide causes down-regulation of the Bcl-2 gene, resulting in control of cell growth in tumors, such as glioblastoma multiformes.

TO THE EDITOR

The recent article by Zhou et al[1] was highly interesting and thought provoking. The authors have clearly shown that triptolide administration is associated with up-regulation of the Bax gene, resulting in an attenuating effect on cell growth in gastrointestinal malignancies, such as pancreatic carcinomas[1]. The article by Zhou et al[1] is all the more important because it highlights the rapidly increasing role of triplodide in the management of systemic malignancies.

For instance, triptolide acts on the PI3K/Akt/NF-κB pathway thereby enhancing apoptosis secondary to the administration of bortezomib in multiple myeloma cells[2]. Similar synergisms are seen when triptolide is administered along with 5-fluoruracil for the management of colonic carcinomas[3]. Similarly, triptolide causes down-regulation of the Bcl-2 gene resulting in control of cell growth in tumors, such as glioblastoma multiformes[4]. In fact, triptolide, when combined with ionizing radiation in the therapy of pancreatic carcinomas, decreases cell survival in these tumors by almost 21%[5].

Triptolide also inhibits the SDF-1/CXCR4 pathway and thereby has an attenuating effect on lymphoid metastatic, as well as proliferative activity in non- Hodgkin lymphoma cell lines[6]. Similarly, triptolide demonstrates anti-proliferative effects in other hematological malignancies, such as acute myeloid leukemia. In fact, the anti-carcinogenic effects of triptolide in malignancies, such as acute myeloid leukemia are markedly enhanced by other agents such as AraC[7]. Recent studies also confirm that triptolide has a negative effect on proliferation in acute T lymphocytic leukemia[8]. These anti-carcinogenic functions of triptolide are in part secondary to its anti- angiogenic properties[9].

More recently, Xu et al[10] have developed polymeric micelles of triptolide which appear to demonstrate anti-carcinogenic properties without affecting host immunity. These recent developments further highlights the immense therapeutic potential of triptiolide and the need for further research to fully assess its anti-carcinogenic potential.