Cordycepin Sensitizes Cholangiocarcinoma Cells to Be Killed by Natural Killer-92 (NK-92) Cells.

Pa-Thai Yenchitsomanus,Yingmanee Tragoolpua,Nunghathai Sawasdee,Suthida Panwong,Thida Kaewkod,Methi Wathikthinnakon,Aussara Panya

doi:10.3390/molecules26195973

Pa-Thai Yenchitsomanus, Yingmanee Tragoolpua + Show 5 more

Open Access

https://doi.org/10.3390/molecules26195973

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Abstract

Immunotherapy harnessing immune functions is a promising strategy for cancer treatment. Tumor sensitization is one approach to enhance tumor cell susceptibility to immune cell cytotoxicity that can be used in combination with immunotherapy to achieve therapeutic efficiency. Cordycepin, a bioactive compound that can be extracted from some Cordyceps spp. has been reported to effectively inhibit tumor growth, however, the mechanism of its tumor sensitization activity that enhances immune cell cytotoxicity is unknown. In the present study, we investigated the potency of cordycepin to sensitize a lethal cancer, cholangiocarcinoma (CCA), to natural killer (NK) cells. Treatment with cordycepin prior to and during co-culturing with NK-92 cells significantly increased cell death of KKU-213A as compared to solitary cordycepin or NK treatment. Moreover, sensitization activity was also observed in the combination of NK-92 cells and Cordyceps militaris extract that contained cordycepin as a major component. The cordycepin treatment remarkably caused an increase in TRAIL receptor (DR4 and DR5) expression in KKU-213A, suggesting the possible involvement of TRAIL signaling in KKU-213A sensitization to NK-92 cells. In conclusion, this is the first report on the sensitization activity of cordycepin on CCA cells to NK cytotoxicity, which supports that cordycepin can be further developed as an alternate immunomodulating agent.

Highlights

Cholangiocarcinomas (CCAs), or bile duct cancers, can be divided into three groups depending on the anatomical location of the tumor in the biliary tree, the locations of which are intrahepatic, distal, and perihilar [1]
An alternative therapeutic approach is needed to combine with systemic chemotherapy, at least to prolong the survival of CCA patients
CCA is exactly the kind of cancer for which standard treatments fail to prolong treatments

Summary

Introduction

Cholangiocarcinomas (CCAs), or bile duct cancers, can be divided into three groups depending on the anatomical location of the tumor in the biliary tree, the locations of which are intrahepatic (iCCA), distal (dCCA), and perihilar (pCCA) [1]. The incidence rates of CCA show geographical variation, with a higher rate of occurrence in Eastern countries [2]. The highest incidence, with a rate of 85/100,000 population, is reported in northeastern. CCA is a deadly cancer with a very poor prognosis due to the fact that most patients are diagnosed at an advanced, unresectable stage [3,4]. The systemic chemotherapy has been used, the prolonged survival rate remains at less than 12 months since CCA commonly resists chemotherapy [5]. An alternative therapeutic approach is needed to combine with systemic chemotherapy, at least to prolong the survival of CCA patients

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