Staurosporine induces apoptosis in pancreatic carcinoma cells PaTu 8988t and Panc-1 via the intrinsic signaling pathway

Manuela Malsy,Anika Bundscherer,Diane Bitzinger,Bernhard Graf

doi:10.1186/s40001-019-0365-x

Manuela Malsy, Anika Bundscherer + Show 2 more

Open Access

https://doi.org/10.1186/s40001-019-0365-x

Copy DOI

Abstract

BackgroundCancer, one of the leading causes of death worldwide, develops when the normal balance between mitosis and apoptosis is disrupted. The subsequently increased proliferation rate or decreased apoptosis rate of cells leads to uncontrolled cellular growth. Thus, the current aim of cancer research is to increase the apoptosis rate in tumor cells—while limiting the concurrent death of healthy cells—and to induce controlled apoptosis in abnormal cells. Staurosporine is a very potent inducer of apoptosis because it inhibits many different kinases. So far, many different kinase pathways of staurosporine-induced apoptosis have been discussed for various tumor entities.AimsTo identify the effect of staurosporine in pancreatic and colorectal carcinoma cells and its apoptosis-inducing signaling pathway.MethodsThe apoptosis rate in pancreatic and colorectal carcinoma cells was analyzed by annexin V staining after staurosporine administration. Staurosporine stimulation and its effects on the expression of Bcl2, BAX, Bad, caspase-8, and caspase-9 were investigated with immunoblot.ResultsStaurosporine significantly increased apoptosis in pancreatic carcinoma cells. Western blot analysis showed activation of caspase-9 in PaTu 8988t and Panc-1 cells with 1 µM staurosporine. In addition, expression of Bcl2 and Bad was decreased in PaTu 8988t cells. In colorectal carcinoma cells SW 480, staurosporine stimulation did not induce apoptosis.ConclusionModern therapeutic strategies for tumor diseases target the efficient modulation of specific signaling and transcription pathways. In this respect, the therapeutic potential of protein kinase inhibitors has been repeatedly discussed. Our study showed that staurosporine induces apoptosis in pancreatic carcinoma cells via the intrinsic signaling pathway. Thus, staurosporine is a suitable positive control for in vitro apoptosis tests for the pancreatic cancer cell lines PaTu 8988t and Panc-1. Further clinical studies should analyze the impact of this finding on cancer treatment.

Highlights

Cancer, one of the leading causes of death worldwide, develops when the normal balance between mitosis and apoptosis is disrupted
Expression of B cell lymphoma 2 (Bcl2) and Bcl2 antagonist of cell death (Bad) was decreased in PaTu 8988t cells
Our study showed that staurosporine induces apoptosis in pancreatic carcinoma cells via the intrinsic signaling pathway

Summary

Introduction

One of the leading causes of death worldwide, develops when the normal balance between mitosis and apoptosis is disrupted. The subsequently increased proliferation rate or decreased apoptosis rate of cells leads to uncontrolled cellular growth. The current aim of cancer research is to increase the apoptosis rate in tumor cells—while limiting the concurrent death of healthy cells—and to induce controlled apoptosis in abnormal cells. Cancer develops when the normal balance between mitosis and apoptosis is disrupted [3]. The subsequent increase in the proliferation rate or the decrease in the apoptosis rate of cells results in uncontrolled cellular growth [4, 5]. The current aim of cancer research is to increase the apoptosis rate in tumor cells—while simultaneously limiting concurrent death of healthy

Methods

Results

Discussion

Conclusion