ABSTRACT
Store-operated calcium entry (SOCE) is an important pathway for calcium signaling that regulates calcium influx across the plasma membrane upon the depletion of calcium stores in the endoplasmic reticulum. SOCE participates in regulating a number of physiological processes including cell proliferation and migration while SOCE dysregulation has been linked with pathophysiological conditions such as inflammation and cancer. The crosslink between cancer and inflammation has been well-established where abundant evidence demonstrate that inflammation plays a role in cancer pathophysiology and the response of cancer cells to chemotherapeutic agents including cisplatin. Indeed, the efficacy of cisplatin against cancer cells is reduced by inflammation. Interestingly, it was shown that SOCE enhances inflammatory signaling in immune cells. Therefore, the main objectives of this study are to examine the impact of SOCE inhibition on the cisplatin sensitivity of breast cancer cells and to explore its related mechanism in modulating the inflammatory response in breast cancer cells. Our findings showed that SOCE inhibitor (BTP2) enhanced cisplatin cytotoxicity against resistant breast cancer cells via inhibition of cell proliferation and migration as well as induction of apoptosis. We also found an upregulation in the gene expression of two major components of SOCE, STIM1 and ORAI1, in cisplatin-resistant breast cancer cells compared to cisplatin-sensitive breast cancer cells. In addition, cisplatin treatment increased the gene expression of STIM1 and ORAI1 in cisplatin-resistant breast cancer cells. Finally, this study also demonstrated that cisplatin therapy caused an increase in the gene expression of inflammatory mediators COX2, IL-8, and TNF-α as well as COX2 protein and upon SOCE inhibition using BTP2, the effect of cisplatin on the inflammatory mediators was reversed. Altogether, this study has proven the pivotal role of SOCE in cisplatin resistance of breast cancer cells and showed the importance of targeting this pathway in improving breast cancer therapy.
ABSTRACT
Background and Objectives: In Saudi Arabia, Acne vulgaris is a very predominant ailment among adolescents, especially female university students, and self-medication has become a trend to manage this condition. To determine the prevalence of Acne vulgaris among health care students and to access the scenario of its self-medication in light of students' knowledge, attitude, and practice towards it. Materials and Methods: This was an observational study conducted at King Saud University, Riyadh, Kingdom of Saudi Arabia, from January 2022 to March 2022. The study was undertaken using a pre-structured questionnaire. Results: A total of 550 university students were recruited and the incidence of acne was observed to be 78.5% (432 out of 550) with a female predominance. A total of 56.0% (244 of 432) students used self-medications for acne without a prescription and the most used prescription drugs were topical and oral antibiotics (38.1%), followed by Isotretinoin (22.55), and topical adaplene (20.9%). Female students (n = 181, 63.5%) were significantly more likely to self-medicate compared to male students (n = 63, 42.9%, p ≤ 0.001). Almost 60% of medical students had proper knowledge of medication for acne. Conclusion: Acne vulgaris is a highly prevalent condition among university students of Saudi Arabia and use of self-medication among acne sufferers is high. Education programs should be made to raise awareness about acne and its treatment.
