Curcumin-Mediated Apoptotic Cell Death in Papillary Thyroid Cancer and Cancer Stem-Like Cells through Targeting of the JAK/STAT3 Signaling Pathway.

The constitutive activation of Janus Kinase/Signal Transducer and Activator of Transcription (JAK/STAT) signal transduction is well elucidated in STAT3-mediated oncogenesis related to thyroid cancer and is considered to be a plausible therapeutic target. Hence, we investigated whether curcumin, a natural compound, can target the JAK/STAT3 signaling pathway to induce cytotoxic effects in papillary thyroid cancer (PTC) cell lines (BCPAP and TPC-1) and derived thyroid cancer stem-like cells (thyrospheres). Curcumin suppressed PTC cell survival in a dose-dependent manner via the induction of caspase-mediated apoptosis and caused the attenuation of constitutively active STAT3 (the dephosphorylation of Tyr705-STAT3) without affecting STAT3. Gene silencing with STAT3-specific siRNA showed the modulation of genes associated with cell growth and proliferation. The cotreatment of PTC cell lines with curcumin and cisplatin synergistically potentiated cytotoxic effects via the suppression of JAK/STAT3 activity along with the inhibition of antiapoptotic genes and the induction of proapoptotic genes, and it also suppressed the migration of PTC cells by downregulating matrix metalloproteinases and the inhibition of colony formation. Finally, thyrospheres treated with curcumin and cisplatin showed suppressed STAT3 phosphorylation, a reduced formation of thyrospheres, and the downregulated expression of stemness markers, in addition to apoptosis. The current study's findings suggest that curcumin synergistically enhances the anticancer activity of cisplatin in PTC cells as well as in cancer stem-like cells by targeting STAT3, which suggests that curcumin combined with chemotherapeutic agents may provide better therapeutic outcomes.

Non-Coding RNAs as Regulators and Markers for Targeting of Breast Cancer and Cancer Stem Cells.

Breast cancer is regarded as a heterogeneous and complicated disease that remains the prime focus in the domain of public health concern. Next-generation sequencing technologies provided a new perspective dimension to non-coding RNAs, which were initially considered to be transcriptional noise or a product generated from erroneous transcription. Even though understanding of biological and molecular functions of noncoding RNA remains enigmatic, researchers have established the pivotal role of these RNAs in governing a plethora of biological phenomena that includes cancer-associated cellular processes such as proliferation, invasion, migration, apoptosis, and stemness. In addition to this, the transmission of microRNAs and long non-coding RNAs was identified as a source of communication to breast cancer cells either locally or systemically. The present review provides in-depth information with an aim at discovering the fundamental potential of non-coding RNAs, by providing knowledge of biogenesis and functional roles of micro RNA and long non-coding RNAs in breast cancer and breast cancer stem cells, as either oncogenic drivers or tumor suppressors. Furthermore, non-coding RNAs and their potential role as diagnostic and therapeutic moieties have also been summarized.