Abstract
Chemotherapy is an essential strategy for cancer treatment. On the other hand, consistent exposure to chemotherapeutic drugs induces chemo-resistance in cancer cells through a variety of mechanisms. Therefore, it is important to develop a new drug inhibiting chemo-resistance. Although hemistepsin A (HsA) is known to have anti-tumor effects, the molecular mechanisms of HsA-mediated cell death are unclear. Accordingly, this study examined whether HsA could induce apoptosis in aggressive prostate cancer cells, along with its underlying mechanism. Using HsA on two prostate cancer cell lines, PC-3 and LNCaP cells, the cell analysis and in vivo xenograft model were assayed. In this study, HsA induced apoptosis and autophagy in PC-3 cells. HsA-mediated ROS production attenuated HsA-induced apoptosis and autophagy after treatment with N-acetyl-L-cysteine (NAC), a ROS scavenger. Moreover, autophagy inhibition by 3-MA or CQ is involved in accelerating the apoptosis induced by HsA. Furthermore, we showed the anti-tumor effects of HsA in mice, as assessed by the reduced growth of the xenografted tumors. In conclusion, HsA induced apoptosis and ROS generation, which were blocked by protective autophagy signaling.
Highlights
Prostate cancer is the second most commonly diagnosed cancer in men, accounting for more than one in five new cancer diagnoses [1,2,3]
This study examined the induction of autophagy by hemistepsin A (HsA) in chemo-resistant prostate cancer cells as a protective role of apoptosis
The results clearly showed that procaspase-3 was suppressed, and poly (ADP-ribose) polymerase (PARP) showed more cleavage by HsA in a dosedependent manner (Figure 1D)
Summary
Prostate cancer is the second most commonly diagnosed cancer in men, accounting for more than one in five new cancer diagnoses [1,2,3]. It has been reported that several studies showed cancer incidence and mortality rates have increased [4,5]. Several new therapies for prostate cancer have been attempted, the fundamental mechanisms of prostate cancer need to be clarified [6,7,8]. Various studies have shown that apoptosis and autophagy are important mechanisms for cancer cell death [7]. Apoptosis is considered a major mechanism for cancer cell death, but these mechanisms do not block chemo-resistant cancer and advanced cancer [8]. Many studies have revealed autophagy as a new and important target mechanism for chemo-resistant cancer therapies [9]. Many cancer cells induce autophagy to block apoptosis [8,10,11]
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