Abstract
Background: Prostate cancer is the second most frequently diagnosed malignancy worldwide. Here, the cytotoxic and antimetastatic effects of a new HDAC6/8 inhibitor, LASSBio-1911, and a new dual-PI3K/HDAC6 inhibitor, LASSBio-2208, were evaluated against PC3 prostate cancer cell line. Methods: A MTT assay was used to assess the cell viability. Annexin V/propidium iodide (PI) was used to detect apoptotic cell death and to analyze the cell cycle distribution. Interleukin 6 (IL-6) levels were measured by ELISA. A cell scratch assay was performed to assess cell migration, and the expression of proteins was estimated by Western blotting. Results: LASSBio-1911 and LASSBio-2208 exert cytotoxic effects against PC3 cells. However, LASSBio-2208 was demonstrated to be more potent than LASSBio-1911. The apoptosis assays showed that both compounds trigger apoptotic processes and cause the arrest of cells in the G2/M phase of the cell cycle. The Western blot analysis revealed that LASSBio-2208 significantly decreased the expression of p-JNK and JAK2. However, both compounds reduced the expression of p-STAT3, IL-6 secretion, and cell migration. Conclusions: LASSBio-1911 and LASSBio-2208 demonstrated significant activity in reducing cell viability and migration. These compounds can be further used as prototypes for the development of new potential anticancer alternative treatments.
Highlights
Prostate cancer is the second most frequently diagnosed malignancy in men worldwide and tends to develop in older men aged 50 years and older [1]
To further evaluate whether both compounds affect cell cycle phases, we studied the effects of LASSBio-1911 and LASSBio-2208 on the cell cycle progression of PC3 cells
We found that both compounds were able to reduce cell viability incubation (Figure 1), but even though LASSBio-1911 was able to affect cell viability, higher after 24 h of incubation (Figure 1), but even though LASSBio-1911 was able to affect cell doses were required than needed for LASSBio-2208 to have the same effect
Summary
Prostate cancer is the second most frequently diagnosed malignancy (after lung cancer) in men worldwide and tends to develop in older men aged 50 years and older [1]. Prostate tumors are often cured when they are still localized; the formation of metastases can occur in up to 25% of patients [2]. The vast majority of patients diagnosed with metastatic disease remain asymptomatic for months to years [3], which makes diagnosis and treatment more difficult. There is an urgent need for new therapeutic agents capable of inhibiting the progression and metastasis of cancer cells during early treatment. Phosphoinositide 3-kinase (PI3K) signaling has emerged as an attractive target for cancer therapy, and many drugs that inhibit various PI3K pathway components are currently in clinical trials. PI3K is a heterodimeric protein that participates in multiple cellular processes, including cell proliferation, transformation, migration, and differentiation [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
