Epigenetic drugs induce the potency of classic chemotherapy, suppress post-treatment re-growth of breast cancer, but preserve the wound healing ability of stem cells.

Epigenetic therapy augments neoadjuvant chemotherapy (NACT) in breast cancer and may aid post-surgical wound healing affected by NACT. Our study investigates: (1) The cytotoxicity of classic paclitaxel chemotherapy on triple negative breast cancer (TNBC) independently and in combination with epigenetic drugs. (2) The sustainable inhibition of breast cancer regrowth following paclitaxel and epigenetic therapies. (3) The effects of paclitaxel with and without epigenetic therapy on the post-treatment viability and wound healing potential of adipose stem cells (ASCs). Cytotoxicity assays were performed on TNBC and ASCs. Cells were treated and recovered in drug-free medium. Cell viability was measured via cell counts and MTT assays. W -ound healing was tested with scratch assays. The combination of epigenetic drugs shows increased toxicity against TNBC cells compared to standard chemotherapy alone. Moreover, the combination of paclitaxel with epigenetic treatments causes cancer toxicity that is sustainable to TNBC cells after the drugs' removal with minimal effect on ASCs wound healing ability. The use of epigenetic drugs in addition to standard chemotherapy is cytotoxic to TNBC cells and prevents post-treatment recovery of TNBC while maintaining ASC wound healing ability. This strategy may be useful in maximizing post-surgical wound healing following NACT in TNBC.

Epigenetic therapy can inhibit growth of ovarian cancer cells and reverse chemoresistant properties acquired from metastatic omentum.

OBJECTIVE: To examine the cytotoxicity of epigenetic drugs independently and in combination with chemotherapy on ovarian cancer cells Caov-3, and to investigate their ability to acquire chemoresistance in omental microenvironments and whether epigenetic drugs can counteract this chemoresistance. METHODS: A pilot study was conducted in Cooper University Hospital, NJ, USA from August 1 to October 31, 2017, among women undergoing surgeries for uterine and ovarian cancer. Cytotoxicity assays using IC50 values of epigenetic drugs and paclitaxel and cisplatin were performed on Caov-3. Omental adipose-derived stem cells (OASCs) were isolated from omentum with/without metastases. Caov-3 was cultured with OASCs' conditioned medium and subjected to different drugs. Cell viability and secretome was measured using MTT and Elisa, respectively. RESULTS: Three women met the eligibility criteria and were included in the study. Epigenetic drugs alone or in combination with chemotherapy showed 85%-94% increased cytotoxicity against Caov-3 (P≤0.005). Metastatic OASCs conditioned medium showed up to 27-fold increase in tumorigenic factors and promoted chemoresistance (28%-35%; P < 0.050) against chemotherapy. Epigenetic therapy resulted in up to a 40-fold reversal in this chemoresistance. CONCLUSION: Epigenetic therapies could have an important role in treating a subgroup of ovarian cancer patients that demonstrate resistance to first-line chemotherapy.